人乳腺癌细胞株miRNAs的差异表达谱及hsa-miR-340对乳腺癌细胞侵袭力的影响
|
摘要
背景:MicroRNAs (miRNAs or miRs)是一类保守的由18-24个核苷酸组成的非编码蛋白的单链RNA。MiRNAs被看作是一类特殊的基因调节因子,通过在转录后水平调节基因的表达而在生物的组织器官发育、脂肪代谢、细胞分化、增殖和凋亡等过程中发挥重要作用。近年来陆续发现,一些miRNAs参与了人类乳腺癌的癌形成、癌演进以及转移过程。虽然已有较多研究报道各种miRNAs在人类癌症中的异常改变,但是它们的生物学功能还没有完全被人们所了解。
目的:检测不同侵袭力人乳腺癌细胞株中miRNAs的表达情况,筛选出与乳腺癌细胞侵袭行为相关的miRNAs;初步探讨miR-340对乳腺癌细胞侵袭力的影响,预测miR-340的靶基因。
方法:
(1)应用miRNAs表达谱芯片检测低侵袭力人乳腺癌细胞株MCF-7和高侵袭力人乳腺癌细胞株MDA-MB-231中具有表达差异的miRNAs。
(2)挑选具有显著表达差异的miR-340作为进一步研究对象,采用QRT-PCR方法验证其在高侵袭力人乳腺癌细胞株(MDA-MB-231和MDA-MB-468)和低侵袭力人乳腺癌细胞株MCF-7中的表达差异。
(3)利用脂质体转染技术将化学合成的miR-340阻遏物(miR-340 inhibitors)转染至人乳腺癌细胞株MCF-7中,通过CCK-8法检测细胞转染前后增殖活性变化,用Transwell侵袭实验检测转染前后细胞侵袭力改变。
(4)利用生物信息学手段,对miR-340进行靶基因预测。
结果:
(1) MiRNAs芯片结果显示,在二种不同侵袭力人乳腺癌细胞株中筛选获得112种差异表达的miRNAs。其中,有34种为显著差异表达的miRNAs。与MDA-MB-231细胞相比,在MCF-7细胞中表达显著上调的有hsa-miR-340、miR-335、miR-126等14个miRNAs,显著下调的有hsa-miR-186、hsa-miR-125b-1*等20个miRNAs。
(2) QRT-PCR反应结果显示,与高侵袭力人乳腺癌细胞株MDA-MB-231和MDA-MB-468相比,miR-340在低侵袭力人乳腺癌细胞株MCF-7中的表达显著上调(P<0.05)。
(3)转染miR-340阻遏物后,乳腺癌细胞的侵袭能力较转染前明显增强(P<0.05),而体外增殖能力无明显变化(P>0.05)。
(4)生物信息学手段预测结果显示,包括CTNNB,ZNF403,CCPG1等基因在内的数十种基因可能是miR-340的靶基因。
结论:
(1)不同侵袭力乳腺癌细胞株中存在多种miRNAs表达差异。
(2) MiR-340对人乳腺癌细胞的侵袭力可能存在负性调控作用,癌细胞中miR-340活性受抑制,可使其侵袭力增强。
(3) MiR-340可能通过某些靶基因发挥其对肿瘤发生发展的调控作用。
Background MicroRNAs (miRNAs or miRs) are conserved, single-stranded, 18-24 nucleotide non-protein-coding RNAs,and they regulate protein expression at post-transcriptional level. MicroRNAs have quite recently emerged as a novel class of gene regulators, which play important roles in many biological processes, including embryonic development, fat metabolism, cell growth, differentiation and apoptosis, and gene regulation. Accelerating research has resulted in some miRNA has took part in the tumorigenesis, invasion and metastasis of human breast cancer. Although alterations of miRNAs in human cancers have been reported, the biological functions of miRNAs are not yet fully understood. Objective To investigate the expression of hsa-miRNAs change in the breast cancer cell lines with differing invasiveness; To investigate the effect of miR-340 to breast cancer cell invasion potential, and to predict potential targets of miR-340. Method (1) To explore differential expression of miRNAs between breast cancer cell line MCF-7 and MDA-MB-231 by miRNA array. (2) The expression of miR-340 in different breast cancer cell lines (MDA-MB-231, MDA-MB-468 and MCF-7) was detected by QRT-PCR. (3) hsa-miR-340 inhibitors was transfected into breast cancer cell line MCF-7 to reduce the activity of miR-340. The impact of miR-340 downregulation on proliferation and invasion potential were evaluated by CCK-8 kit and invasion assay. The possible target genes of miR-340 were forecasted by bioinformatics tools. (4) The possible target genes of miRNA-340 were forecasted by bioinformatics tools. Results (1) There were 112 altered miRNAs between breast cancer cell line MCF-7 and MDA-MB-231.Compared with breast cancer cell line MDA-MB-231 , there were 34 kinds of miRNAs altered significantly in breast cancer cell line MCF-7,of which 14 miRNAs were upregulated (hsa-miR-340、miR-335、miR-126,et al), 20 miRNAs were downregulated( hsa-miR-186、hsa-miR-125b -1*,et al). (2) The results of QRT-PCR showed that the expression of miR-340 was upregulated significantly in the lower invasion potential breast cell line MCF-7 compared with higher invasion potential breast cancer cell lines MDA-MB-231 and MDA-MB-468 (P<0.05). (3) Transfected cells showed a higher invasion potential than untransfected cells as miR-340 had been downregulated (P<0.05), but the proliferation has no significantly change (P>0.05). (4) Using bioinformatics tools, saveral possible target genes of miRNA-340 were forecasted, including CTNNB, ZNF403 and CCPG1. Conclusion (1) The altered expression of miRNAs exist in the breast cancer cell lines with different invasive ability. (2) MiR-340 may negatively regulate the invasiveness possible of breast cancer cells, and cancer cells showed a higher invasion potential after the activity of miR-340 was reduced. (3) MiR-340 play important roles in carcinogenesis and cancer progression by regulating the possible target genes.
目的:检测不同侵袭力人乳腺癌细胞株中miRNAs的表达情况,筛选出与乳腺癌细胞侵袭行为相关的miRNAs;初步探讨miR-340对乳腺癌细胞侵袭力的影响,预测miR-340的靶基因。
方法:
(1)应用miRNAs表达谱芯片检测低侵袭力人乳腺癌细胞株MCF-7和高侵袭力人乳腺癌细胞株MDA-MB-231中具有表达差异的miRNAs。
(2)挑选具有显著表达差异的miR-340作为进一步研究对象,采用QRT-PCR方法验证其在高侵袭力人乳腺癌细胞株(MDA-MB-231和MDA-MB-468)和低侵袭力人乳腺癌细胞株MCF-7中的表达差异。
(3)利用脂质体转染技术将化学合成的miR-340阻遏物(miR-340 inhibitors)转染至人乳腺癌细胞株MCF-7中,通过CCK-8法检测细胞转染前后增殖活性变化,用Transwell侵袭实验检测转染前后细胞侵袭力改变。
(4)利用生物信息学手段,对miR-340进行靶基因预测。
结果:
(1) MiRNAs芯片结果显示,在二种不同侵袭力人乳腺癌细胞株中筛选获得112种差异表达的miRNAs。其中,有34种为显著差异表达的miRNAs。与MDA-MB-231细胞相比,在MCF-7细胞中表达显著上调的有hsa-miR-340、miR-335、miR-126等14个miRNAs,显著下调的有hsa-miR-186、hsa-miR-125b-1*等20个miRNAs。
(2) QRT-PCR反应结果显示,与高侵袭力人乳腺癌细胞株MDA-MB-231和MDA-MB-468相比,miR-340在低侵袭力人乳腺癌细胞株MCF-7中的表达显著上调(P<0.05)。
(3)转染miR-340阻遏物后,乳腺癌细胞的侵袭能力较转染前明显增强(P<0.05),而体外增殖能力无明显变化(P>0.05)。
(4)生物信息学手段预测结果显示,包括CTNNB,ZNF403,CCPG1等基因在内的数十种基因可能是miR-340的靶基因。
结论:
(1)不同侵袭力乳腺癌细胞株中存在多种miRNAs表达差异。
(2) MiR-340对人乳腺癌细胞的侵袭力可能存在负性调控作用,癌细胞中miR-340活性受抑制,可使其侵袭力增强。
(3) MiR-340可能通过某些靶基因发挥其对肿瘤发生发展的调控作用。
Background MicroRNAs (miRNAs or miRs) are conserved, single-stranded, 18-24 nucleotide non-protein-coding RNAs,and they regulate protein expression at post-transcriptional level. MicroRNAs have quite recently emerged as a novel class of gene regulators, which play important roles in many biological processes, including embryonic development, fat metabolism, cell growth, differentiation and apoptosis, and gene regulation. Accelerating research has resulted in some miRNA has took part in the tumorigenesis, invasion and metastasis of human breast cancer. Although alterations of miRNAs in human cancers have been reported, the biological functions of miRNAs are not yet fully understood. Objective To investigate the expression of hsa-miRNAs change in the breast cancer cell lines with differing invasiveness; To investigate the effect of miR-340 to breast cancer cell invasion potential, and to predict potential targets of miR-340. Method (1) To explore differential expression of miRNAs between breast cancer cell line MCF-7 and MDA-MB-231 by miRNA array. (2) The expression of miR-340 in different breast cancer cell lines (MDA-MB-231, MDA-MB-468 and MCF-7) was detected by QRT-PCR. (3) hsa-miR-340 inhibitors was transfected into breast cancer cell line MCF-7 to reduce the activity of miR-340. The impact of miR-340 downregulation on proliferation and invasion potential were evaluated by CCK-8 kit and invasion assay. The possible target genes of miR-340 were forecasted by bioinformatics tools. (4) The possible target genes of miRNA-340 were forecasted by bioinformatics tools. Results (1) There were 112 altered miRNAs between breast cancer cell line MCF-7 and MDA-MB-231.Compared with breast cancer cell line MDA-MB-231 , there were 34 kinds of miRNAs altered significantly in breast cancer cell line MCF-7,of which 14 miRNAs were upregulated (hsa-miR-340、miR-335、miR-126,et al), 20 miRNAs were downregulated( hsa-miR-186、hsa-miR-125b -1*,et al). (2) The results of QRT-PCR showed that the expression of miR-340 was upregulated significantly in the lower invasion potential breast cell line MCF-7 compared with higher invasion potential breast cancer cell lines MDA-MB-231 and MDA-MB-468 (P<0.05). (3) Transfected cells showed a higher invasion potential than untransfected cells as miR-340 had been downregulated (P<0.05), but the proliferation has no significantly change (P>0.05). (4) Using bioinformatics tools, saveral possible target genes of miRNA-340 were forecasted, including CTNNB, ZNF403 and CCPG1. Conclusion (1) The altered expression of miRNAs exist in the breast cancer cell lines with different invasive ability. (2) MiR-340 may negatively regulate the invasiveness possible of breast cancer cells, and cancer cells showed a higher invasion potential after the activity of miR-340 was reduced. (3) MiR-340 play important roles in carcinogenesis and cancer progression by regulating the possible target genes.
引文
1. Jemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor A, Feuer EJ, Thun MJ. Cancer statistics, 2005. CA Cancer J Clin.2005; 55(1):10-30.
2. Farber E.The multistep nature of cancer development.Cancer Res. 1984;44(10):4217-4223.
3. Nilsen TW. Mechanisms of microRNA-mediated gene regulation in animal cells [J]. Trends Genet, 2007;23(5):243-249.
4. Morlando M, Ballarino M, Gromak N, Pagano F, Bozzoni I, Proudfoot NJ. Primary microRNA transcripts are processed co-transcriptionally [J]. Nat Struct Mol Biol. 2008;15(9):902-909.
5. Liu X, Fortin K, Mourelatos Z. MicroRNAs: Biogenesis and molecular functions [J]. Brain Pathol. 2008;18(1):113–121.
6. Iorio MV, Ferracin M, Liu CG, Veronese A, Spizzo R, Sabbioni S, Magri E, Pedriali M, Fabbri M, Campiglio M, Ménard S, Palazzo JP, Rosenberg A, Musiani P, Volinia S, Nenci I, Calin GA, Querzoli P, Negrini M, Croce CM. MicroRNA Gene Expression Deregulation in Human Breast Cancer [J]. Cancer Res, 2005;65(16):7065-7070.
7. Zhu S, Wu H, Wu F, Nie D, Sheng S, Mo YY. MicroRNA-21 targets tumor suppressor genes in invasion and metastasis [J]. Cell Research, 2008;18(3):350-359.
8. Foekens JA, Sieuwerts AM, Smid M, Look MP, de Weerd V, Boersma AW, Klijn JG, Wiemer EA, Martens JW. Four miRNAs associated with aggressiveness of lymph node-negative, estrogen receptor-positive human breast cancer [J]. Proc Natl Acad Sci U S A. 2008;105(35):13021-13026.2009;113(2): 249-255.
27.张辉,苏式兵,周钱梅,陆亦宇.乳腺癌细胞与乳腺上皮细胞MicroRNAs表达谱的差异性分析[J].癌症, 2009, 28 (5):493-499.
28. Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, Visone R, Iorio M, Roldo C, Ferracin M, Prueitt RL, Yanaihara N, Lanza G, Scarpa A, Vecchione A, Negrini M, Harris CC, Croce CM. A microRNA expression signature of human solid tumors defines cancer gene targets [J]. Proc Natl Acad Sci U S A. 2006;103(7):2257-2261.
29. Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, Downing JR, Jacks T, Horvitz HR, Golub TR. MicroRNA expression profiles classify human cancers [J]. Nature. 2005; 435 (7043):834-838.
30. Hossain A, Kuo MT, Saunders GF. Mir-17-5p regulates breast cancer cell proliferation by inhibiting translation of AIB1 mRNA [J]. Mol Cell Biol. 2006;26(21):8191-8201.
31. Gordon LA, Mulligan KT, Maxwell-Jones H, Adams M, Walker RA, Jones JL. Breast cell invasive potential relates to the myoepithelial phenotype [J]. Int J Cancer. 2003;106(1):8-16.
32. Chen M, Towers LN, O'Connor KL. LPA2 (EDG4) mediates Rho-dependent chemotaxis with lower efficacy than LPA1 (EDG2) in breast carcinoma cells [J]. Am J Physiol Cell Physiol. 2007;292(5):1927-1933.
33. Sheridan C, Kishimoto H, Fuchs RK, Mehrotra S, Bhat-Nakshatri P, Turner CH, Goulet R Jr, Badve S, Nakshatri H. CD44+/CD24- breast cancer cells exhibit enhanced invasive properties: an early step necessary for metastasis[J].Breast Cancer Res. 2006;8(5):R59.
34. Zeng Y, Wagner EJ, Cullen BR. Both natural and designed microRNAs can inhibit the expression of cognate mRNAs when expressed in human cells [J]. Mol Cell.2002;9(6):1327-1233.
35. Zhao Y, Ransom JF, Li A, Vedantham V, von Drehle M, Muth AN, Tsuchihashi T, McManus MT, Schwartz RJ, Srivastava D. Dysregulation of cardiogenesis, cardiac conduction, and cell cycle in mice lacking miRNA-1-2 [J]. Cell. 2007;129(2):303-317.
36. Cheng AM, Byrom MW, Shelton J, Ford LP.Antisense inhibition of human miRNAs and indications for an involvement of miRNA in cell growth and apoptosis [J].Nucleic Acids Res. 2005;33(4):1290-1297.
37. http://www.genepharma.com/cn/product13.asp
38. Sugiyama M, Matsuura M, Takeuchi Y, Kosaka J, Nango M, Oku N. Possible mechanism of polycation liposome (PCL)-mediated gene transfer[J]. Biochim Biophys Acta. 2004;1660(1-2):24-30.
39. Kaiser S, Toborek M. Liposome-Mediated High-Efficiency Transfection of Human Endothelial Cells[J]. J Vasc Res. 2001;38(2):133–143.
40. http://www.sirna.cn/mirna.aspx
41. Stark A, Brennecke J, Bushati N, Russell RB, Cohen SM. Animal MicroRNAs confer robustness to gene expression and have a significant impact on 3'UTR evolution[J].Cell. 2005;123(6):1133-1146.
42. Enright AJ, John B, Gaul U, Tuschl T, Sander C, Marks DS. MicroRNA targets in Drosophila [J]. Genome Biol. 2003;5(1):R1.
43. Lewis BP, Burge CB, Bartel DP.Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets[J].Cell. 2005;120(1):15-20.
44. Krek A, Grün D, Poy MN, Wolf R, Rosenberg L, Epstein EJ, MacMenamin P, da Piedade I, Gunsalus KC, Stoffel M, Rajewsky N. Combinatorial microRNA target predictions [J]. Nat Genet. 2005;37(5):495-500.
45. Grün D, Wang YL, Langenberger D, Gunsalus KC, Rajewsky N.microRNA targetpredictions across seven Drosophila species and comparison to mammalian targets [J]. PLoS Comput Biol. 2005;1(1):e13.
46. http://ibi.zju.edu.cn/bioinplant/
47. Rajewsky N. microRNA target predictions in animals [J]. Nat Genet. 2006;38 Suppl:S8-13.
48. Alexiou P, Maragkakis M, Papadopoulos GL, Simmosis VA, Zhang L, Hatzigeorgiou AG.. The DIANA-mirExTra web server: from gene expression data to microRNA function [J]. PLoS One. 2010;5(2):e9171.
49. Thadani R, Tammi MT. MicroTar: predicting microRNA targets from RNA duplexes [J]. BMC Bioinformatics. 2006;7 Suppl 5:S20.
50. Gene Ontology Consortium.The Gene Ontology in 2010: extensions and refinements.The Gene Ontology in 2010: extensions and refinements [J].Nucleic Acids Res. 2010;38(Database issue):D331-335.
51. Moh MC, Shen S. The roles of cell adhesion molecules in tumor suppression and cell migration: a new paradox [J]. Cell Adh Migr. 2009;3(4):334-336.
1. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics [J]. CA Cancer J Clin. 2005; 55(2):74–108.
2. Houssami N, Anderson BO. Would the real breast cancer please stand up? A global perspective of breast cancer [J]. The Breast. 2008;17(3):217-219.
3. Morlando M, Ballarino M, Gromak N, Pagano F, Bozzoni I, Proudfoot NJ. Primary microRNA transcripts are processed co-transcriptionally [J]. Nat Struct Mol Biol. 2008;15(9):902-909.
4. Hannon GJ. RNA interference [J]. Nature. 2002;418(6894):244-251.
5. Lee Y, Ahn C, Han J, Choi H, Kim J, Yim J, Lee J, Provost P, R?dmark O, Kim S, Kim VN. The nuclear RNase III Drosha initiates microRNA processing [J]. Nature. 2003;425(6956):415-419.
6. Han J, Pedersen JS, Kwon SC, Belair CD, Kim YK, Yeom KH, Yang WY, Haussler D, Blelloch R, Kim VN. Posttranscriptional Crossregulation between Drosha and DGCR8 [J]. Cell. 2009;136(1):75-84
7. Lund E, Guttinger S, Calado A, Dahlberg JE, Kutay U. Nuclear export of microRNA precursors. Science [J]. 2004;303(5654):95–98
8. Bohnsack MT, Czaplinski K, Gorlich D. Exportin 5 is a RanGTP-dependent dsRNA-binding protein that mediates nuclear export of premiRNAs [J]. RNA. 2004; 10(2):185–191
9. Mourelatos Z, Dostie J, Paushkin S, Sharma A, Charroux B, Abel L, Rappsilber J, Mann M, Dreyfuss G.. miRNPs: anovel class of ribonucleoproteins containing numerous microRNAs [J]. Genes Dev. 2002; 16(6), 720–728.
10. Liu X, Fortin K, Mourelatos Z. MicroRNAs: Biogenesis and molecular functions [J]. Brain Pathol. 2008;18(1):113–121.
11. Meister G., Landthaler M, Patkaniowska A, Dorsett Y, Teng G., Tuschl T. HumanArgonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs [J]. Mol Cell. 2004;15(2), 185–197.
12. Rand TA, Ginalski K, Grishin NV, Wang X. Biochemical identification of Argonaute 2 as the sole protein required for RNA-induced silencing complex activity [J]. Proc Natl Acad Sci U S A. 2004;101(40):14385-14389.
13. Rivas FV, Tolia NH, Song JJ, Aragon JP, Liu J, Hannon GJ, Joshua-Tor L. Purified Argonaute2 and an siRNA form recombinant human RISC [J]. Nat Struct Mol Biol. 2005;12(4):340-349.
14. Hutvágner G, Zamore PD. A microRNA in a multiple-turnover RNAi enzyme complex [J]. Science. 2002;297(5589):2056-2060.
15. Nilsen TW. Mechanisms of microRNA-mediated gene regulation in animal cells. Trends Genet [J]. Trends Genet. 2007;23(5):243-249.
16. Schwarz DS, Hutvágner G, Du T, Xu Z, Aronin N, Zamore PD. Asymmetry in the assembly of the RNAi enzyme complex [J]. Cell. 2003;115(2):199-208.
17. Sevignani C, Calin GA, Siracusa LD, Croce CM. Mammalian microRNAs: a small world for fine-tuning gene expression [J]. Mamm Genome 2006;17(3):189-202.
18. Zhang B, Wang Q, Pan X. MicroRNAs and their regulatory roles in animals and plants [J]. J Cell Physiol. 2007;210(2):279-289.
19. Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T. Identification of novel genes coding for small expressed RNAs [J]. Science.2001; 294(5543): 853–858.
20. Lau NC, Lim LP, Weinstein EG, Bartel DP. An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans [J]. Science.2001; 294(5543): 858–862.
21. Lee RC, Ambros V. An extensive class of small RNAs in Caenorhabditis elegans [J]. Science. 2001;294(5543): 862–864.
22. Kedde M, Strasser MJ, Boldajipour B, Oude Vrielink JA, Slanchev K, le Sage C, Nagel R, Voorhoeve PM, van Duijse J, ?rom UA, Lund AH, Perrakis A, Raz E,Agami R. RNA-Binding Protein Dnd1 Inhibits MicroRNA Access to Target mRNA [J]. Cell. 2007;131(7):1273-1286.
23. Culjkovic B, Topisirovic I, Skrabanek L, Ruiz-Gutierrez M, Borden KL. eIF4E is a central node of an RNA regulon that governs cellular proliferation [J]. J Cell Biol. 2006;175(3):415-426.
24. Larsson O, Perlman DM, Fan D, Reilly CS, Peterson M, Dahlgren C, Liang Z, Li S, Polunovsky VA, Wahlestedt C, Bitterman PB. Apoptosis resistance downstream of EIF4E: posttranscriptional activation of an anti-apoptotic transcript carrying a consensus hairpin structure [J]. Nucleic Acids Res. 2006;34(16):4375-4386.
25. Eulalio A, Huntzinger E, Izaurralde E. GW182 interaction with Argonaute is essential for miRNA-mediated translational repression and mRNA decay [J]. Nat Struct Mol Biol. 2008;15(4):346-353.
26. López de Silanes I, Zhan M, Lal A, Yang X, Gorospe M. Identification of a target RNA motif for RNA-binding protein HuR [J]. Proc Natl Acad Sci U S A. 2004;101(9):2987-2992.
27. Bhattacharyya SN, Habermacher R, Martine U, Closs EI, Filipowicz W. Relief of microRNA-mediated translational repression in human cells subjected to stress [J]. Cell. 2006;125(6):1111-1124.
28. Vasudevan S, Tong Y, Steitz JA. Switching from repression to activation: microRNAs can up-regulate translation [J]. Science.2007; 318(5858), 1931–1934.
29. Iorio MV, Ferracin M, Liu CG, Veronese A, Spizzo R, Sabbioni S, Magri E, Pedriali M, Fabbri M, Campiglio M, Ménard S, Palazzo JP, Rosenberg A, Musiani P, Volinia S, Nenci I, Calin GA, Querzoli P, Negrini M, Croce CM.MicroRNA Gene Expression Deregulation in Human Breast Cancer [J]. Cancer Res. 2005;65(16):7065-7070.
30. Tavazoie SF, Alarcón C, Oskarsson T, Padua D, Wang Q, Bos PD, Gerald WL, MassaguéJ. Endogenous human microRNAs that suppress breast cancer metastasislet-7 Regulates Self Renewal and Tumorigenicity of Breast Cancer Cell let-7 Regulates Self Renewal and Tumorigenicity of Breast Cancer Cell [J]. Nature. 2008;451(7175):147-152.
31. Yu F, Yao H, Zhu P, Zhang X, Pan Q, Gong C, Huang Y, Hu X, Su F, Lieberman J, Song E. let-7 Regulates Self Renewal and Tumorigenicity of Breast Cancer Cells [J]. Cell. 2007; 131(6):1109-1123.
32. Gregory PA, Bert AG, Paterson EL, Barry SC, Tsykin A, Farshid G, Vadas MA, Khew-Goodall Y, Goodall GJ. The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1 [J]. Nat Cell Biol. 2008;10(5):593-601.
33. Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, Visone R, Iorio M, Roldo C, Ferracin M, Prueitt RL, Yanaihara N, Lanza G, Scarpa A, Vecchione A, Negrini M, Harris CC, Croce CM. A microRNA expression signature of human solid tumors defines cancer gene targets [J]. Proc Natl Acad Sci U S A. 2006;103(7):2257-2261.
34. Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, Downing JR, Jacks T, Horvitz HR, Golub TR. MicroRNA expression profiles classify human cancers [J]. Nature. 2005; 435 (7043):834-838.
35. Hossain A, Kuo MT, Saunders GF. Mir-17-5p regulates breast cancer cell proliferation by inhibiting translation of AIB1 mRNA [J]. Mol Cell Biol. 2006;26(21):8191-8201.
36. http://www.sirna.cn/mirna.aspx
37.张辉,苏式兵,周钱梅,陆亦宇.乳腺癌细胞与乳腺上皮细胞MicroRNAs表达谱的差异性分析[J].癌症, 2009, 28 (5):493-499.
38. Shen J, Ambrosone CB, Zhao H. Novel genetic variants in microRNA genes and familial breast cancer [J]. Int J Cancer. 2009;124(5):1178-1182.
39. Lu Z, Liu M, Stribinskis V, Klinge CM, Ramos KS, Colburn NH, Li Y. MicroRNA-21 promotes cell transformation by targeting the programmed cell death 4 gene [J]. Oncogene. 2008;27(31):4373-4379.
40. Frankel LB, Christoffersen NR, Jacobsen A, Lindow M, Krogh A, Lund AH. Programmed Cell Death 4 (PDCD4) Is an Important Functional Target of the MicroRNA miR-21 in Breast Cancer Cells [J]. J Biol Chem. 2008;283(2):1026-1033.
41. Yu Z, Wang C, Wang M, Li Z, Casimiro MC, Liu M, Wu K, Whittle J, Ju X, Hyslop T, McCue P, Pestell RG.. A cyclin D1/microRNA 17/20 regulatory feedback loop in control of breast cancer cell proliferation [J]. J Cell Biol. 2008; 182(3): 509–517.
42. O'Donnell KA, Wentzel EA, Zeller KI, Dang CV, Mendell JT. c-Myc-regulated microRNAs modulate E2F1 expression [J]. Nature. 2005;435(7043):839-843.
43. Negrini M, Calin GA. Breast cancer metastasis: a microRNA story [J]. Breast Cancer Res. 2008;10(2):203.
44. Yan LX, Huang XF, Shao Q, Huang MY, Deng L, Wu QL, Zeng YX, Shao JY.MicroRNA miR-21 overexpression in human breast cancer is associated with advanced clinical stage, lymph node metastasis and patient poor prognosis [J]. RNA. 2008;14(11):2348-2360.
45. Zhu S, Wu H, Wu F, Nie D, Sheng S, Mo YY. MicroRNA-21 targets tumor suppressor genes in invasion and metastasis [J]. Cell Res.2008;18(3):350-359.
46. Scott GK, Goga A, Bhaumik D, Berger CE, Sullivan CS, Benz CC. Coordinate suppression of ERBB2 and ERBB3 by enforced expression of micro-RNA miR-125a or miR-125b [J]. J Biol Chem. 2007;282(2):1479-1486.
47. Zhu S, Si ML, Wu H, Mo YY. MicroRNA-21 targets the tumor suppressor gene Tropomyosin 1(TPM1) [J]. J Biol Chem. 2007; 282(19):14328-14336.
48. Sempere LF, Christensen M, Silahtaroglu A, Bak M, Heath CV, Schwartz G, Wells W, Kauppinen S, Cole CN. Altered MicroRNA Expression Confined to SpecificEpithelial Cell Subpopulations in Breast Cancer [J]. Cancer Res. 2007;67(24):11612-11620.
49. Foekens JA, Sieuwerts AM, Smid M, Look MP, de Weerd V, Boersma AW, Klijn JG, Wiemer EA, Martens JW. Four miRNAs associated with aggressiveness of lymph node-negative, estrogen receptor-positive human breast cancer [J]. Proc Natl Acad Sci U S A. 2008;105(35):13021-13026.
50. Ma L, Teruya-Feldstein J, Weinberg RA. Tumour invasion and metastasis initiated by microRNA-10b in breast cancer [J]. Nature. 2007;449(7163):682-688.
51. Reddy SD, Ohshiro K, Rayala SK, Kumar R. MicroRNA-7, a homeobox D10 target, inhibits p21-activated kinase 1 and regulates its functions. Cancer Res. 2008;68(20):8195-8200.
52. Camps C, Buffa FM, Colella S, Moore J, Sotiriou C, Sheldon H, Harris AL, Gleadle JM, Ragoussis J. hsa-miR-210 Is Induced by Hypoxia and Is an Independent Prognostic Factor in Breast Cancer [J]. Clin Cancer Res.2008; 14(5):1340-1348.
2. Farber E.The multistep nature of cancer development.Cancer Res. 1984;44(10):4217-4223.
3. Nilsen TW. Mechanisms of microRNA-mediated gene regulation in animal cells [J]. Trends Genet, 2007;23(5):243-249.
4. Morlando M, Ballarino M, Gromak N, Pagano F, Bozzoni I, Proudfoot NJ. Primary microRNA transcripts are processed co-transcriptionally [J]. Nat Struct Mol Biol. 2008;15(9):902-909.
5. Liu X, Fortin K, Mourelatos Z. MicroRNAs: Biogenesis and molecular functions [J]. Brain Pathol. 2008;18(1):113–121.
6. Iorio MV, Ferracin M, Liu CG, Veronese A, Spizzo R, Sabbioni S, Magri E, Pedriali M, Fabbri M, Campiglio M, Ménard S, Palazzo JP, Rosenberg A, Musiani P, Volinia S, Nenci I, Calin GA, Querzoli P, Negrini M, Croce CM. MicroRNA Gene Expression Deregulation in Human Breast Cancer [J]. Cancer Res, 2005;65(16):7065-7070.
7. Zhu S, Wu H, Wu F, Nie D, Sheng S, Mo YY. MicroRNA-21 targets tumor suppressor genes in invasion and metastasis [J]. Cell Research, 2008;18(3):350-359.
8. Foekens JA, Sieuwerts AM, Smid M, Look MP, de Weerd V, Boersma AW, Klijn JG, Wiemer EA, Martens JW. Four miRNAs associated with aggressiveness of lymph node-negative, estrogen receptor-positive human breast cancer [J]. Proc Natl Acad Sci U S A. 2008;105(35):13021-13026.2009;113(2): 249-255.
27.张辉,苏式兵,周钱梅,陆亦宇.乳腺癌细胞与乳腺上皮细胞MicroRNAs表达谱的差异性分析[J].癌症, 2009, 28 (5):493-499.
28. Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, Visone R, Iorio M, Roldo C, Ferracin M, Prueitt RL, Yanaihara N, Lanza G, Scarpa A, Vecchione A, Negrini M, Harris CC, Croce CM. A microRNA expression signature of human solid tumors defines cancer gene targets [J]. Proc Natl Acad Sci U S A. 2006;103(7):2257-2261.
29. Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, Downing JR, Jacks T, Horvitz HR, Golub TR. MicroRNA expression profiles classify human cancers [J]. Nature. 2005; 435 (7043):834-838.
30. Hossain A, Kuo MT, Saunders GF. Mir-17-5p regulates breast cancer cell proliferation by inhibiting translation of AIB1 mRNA [J]. Mol Cell Biol. 2006;26(21):8191-8201.
31. Gordon LA, Mulligan KT, Maxwell-Jones H, Adams M, Walker RA, Jones JL. Breast cell invasive potential relates to the myoepithelial phenotype [J]. Int J Cancer. 2003;106(1):8-16.
32. Chen M, Towers LN, O'Connor KL. LPA2 (EDG4) mediates Rho-dependent chemotaxis with lower efficacy than LPA1 (EDG2) in breast carcinoma cells [J]. Am J Physiol Cell Physiol. 2007;292(5):1927-1933.
33. Sheridan C, Kishimoto H, Fuchs RK, Mehrotra S, Bhat-Nakshatri P, Turner CH, Goulet R Jr, Badve S, Nakshatri H. CD44+/CD24- breast cancer cells exhibit enhanced invasive properties: an early step necessary for metastasis[J].Breast Cancer Res. 2006;8(5):R59.
34. Zeng Y, Wagner EJ, Cullen BR. Both natural and designed microRNAs can inhibit the expression of cognate mRNAs when expressed in human cells [J]. Mol Cell.2002;9(6):1327-1233.
35. Zhao Y, Ransom JF, Li A, Vedantham V, von Drehle M, Muth AN, Tsuchihashi T, McManus MT, Schwartz RJ, Srivastava D. Dysregulation of cardiogenesis, cardiac conduction, and cell cycle in mice lacking miRNA-1-2 [J]. Cell. 2007;129(2):303-317.
36. Cheng AM, Byrom MW, Shelton J, Ford LP.Antisense inhibition of human miRNAs and indications for an involvement of miRNA in cell growth and apoptosis [J].Nucleic Acids Res. 2005;33(4):1290-1297.
37. http://www.genepharma.com/cn/product13.asp
38. Sugiyama M, Matsuura M, Takeuchi Y, Kosaka J, Nango M, Oku N. Possible mechanism of polycation liposome (PCL)-mediated gene transfer[J]. Biochim Biophys Acta. 2004;1660(1-2):24-30.
39. Kaiser S, Toborek M. Liposome-Mediated High-Efficiency Transfection of Human Endothelial Cells[J]. J Vasc Res. 2001;38(2):133–143.
40. http://www.sirna.cn/mirna.aspx
41. Stark A, Brennecke J, Bushati N, Russell RB, Cohen SM. Animal MicroRNAs confer robustness to gene expression and have a significant impact on 3'UTR evolution[J].Cell. 2005;123(6):1133-1146.
42. Enright AJ, John B, Gaul U, Tuschl T, Sander C, Marks DS. MicroRNA targets in Drosophila [J]. Genome Biol. 2003;5(1):R1.
43. Lewis BP, Burge CB, Bartel DP.Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets[J].Cell. 2005;120(1):15-20.
44. Krek A, Grün D, Poy MN, Wolf R, Rosenberg L, Epstein EJ, MacMenamin P, da Piedade I, Gunsalus KC, Stoffel M, Rajewsky N. Combinatorial microRNA target predictions [J]. Nat Genet. 2005;37(5):495-500.
45. Grün D, Wang YL, Langenberger D, Gunsalus KC, Rajewsky N.microRNA targetpredictions across seven Drosophila species and comparison to mammalian targets [J]. PLoS Comput Biol. 2005;1(1):e13.
46. http://ibi.zju.edu.cn/bioinplant/
47. Rajewsky N. microRNA target predictions in animals [J]. Nat Genet. 2006;38 Suppl:S8-13.
48. Alexiou P, Maragkakis M, Papadopoulos GL, Simmosis VA, Zhang L, Hatzigeorgiou AG.. The DIANA-mirExTra web server: from gene expression data to microRNA function [J]. PLoS One. 2010;5(2):e9171.
49. Thadani R, Tammi MT. MicroTar: predicting microRNA targets from RNA duplexes [J]. BMC Bioinformatics. 2006;7 Suppl 5:S20.
50. Gene Ontology Consortium.The Gene Ontology in 2010: extensions and refinements.The Gene Ontology in 2010: extensions and refinements [J].Nucleic Acids Res. 2010;38(Database issue):D331-335.
51. Moh MC, Shen S. The roles of cell adhesion molecules in tumor suppression and cell migration: a new paradox [J]. Cell Adh Migr. 2009;3(4):334-336.
1. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics [J]. CA Cancer J Clin. 2005; 55(2):74–108.
2. Houssami N, Anderson BO. Would the real breast cancer please stand up? A global perspective of breast cancer [J]. The Breast. 2008;17(3):217-219.
3. Morlando M, Ballarino M, Gromak N, Pagano F, Bozzoni I, Proudfoot NJ. Primary microRNA transcripts are processed co-transcriptionally [J]. Nat Struct Mol Biol. 2008;15(9):902-909.
4. Hannon GJ. RNA interference [J]. Nature. 2002;418(6894):244-251.
5. Lee Y, Ahn C, Han J, Choi H, Kim J, Yim J, Lee J, Provost P, R?dmark O, Kim S, Kim VN. The nuclear RNase III Drosha initiates microRNA processing [J]. Nature. 2003;425(6956):415-419.
6. Han J, Pedersen JS, Kwon SC, Belair CD, Kim YK, Yeom KH, Yang WY, Haussler D, Blelloch R, Kim VN. Posttranscriptional Crossregulation between Drosha and DGCR8 [J]. Cell. 2009;136(1):75-84
7. Lund E, Guttinger S, Calado A, Dahlberg JE, Kutay U. Nuclear export of microRNA precursors. Science [J]. 2004;303(5654):95–98
8. Bohnsack MT, Czaplinski K, Gorlich D. Exportin 5 is a RanGTP-dependent dsRNA-binding protein that mediates nuclear export of premiRNAs [J]. RNA. 2004; 10(2):185–191
9. Mourelatos Z, Dostie J, Paushkin S, Sharma A, Charroux B, Abel L, Rappsilber J, Mann M, Dreyfuss G.. miRNPs: anovel class of ribonucleoproteins containing numerous microRNAs [J]. Genes Dev. 2002; 16(6), 720–728.
10. Liu X, Fortin K, Mourelatos Z. MicroRNAs: Biogenesis and molecular functions [J]. Brain Pathol. 2008;18(1):113–121.
11. Meister G., Landthaler M, Patkaniowska A, Dorsett Y, Teng G., Tuschl T. HumanArgonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs [J]. Mol Cell. 2004;15(2), 185–197.
12. Rand TA, Ginalski K, Grishin NV, Wang X. Biochemical identification of Argonaute 2 as the sole protein required for RNA-induced silencing complex activity [J]. Proc Natl Acad Sci U S A. 2004;101(40):14385-14389.
13. Rivas FV, Tolia NH, Song JJ, Aragon JP, Liu J, Hannon GJ, Joshua-Tor L. Purified Argonaute2 and an siRNA form recombinant human RISC [J]. Nat Struct Mol Biol. 2005;12(4):340-349.
14. Hutvágner G, Zamore PD. A microRNA in a multiple-turnover RNAi enzyme complex [J]. Science. 2002;297(5589):2056-2060.
15. Nilsen TW. Mechanisms of microRNA-mediated gene regulation in animal cells. Trends Genet [J]. Trends Genet. 2007;23(5):243-249.
16. Schwarz DS, Hutvágner G, Du T, Xu Z, Aronin N, Zamore PD. Asymmetry in the assembly of the RNAi enzyme complex [J]. Cell. 2003;115(2):199-208.
17. Sevignani C, Calin GA, Siracusa LD, Croce CM. Mammalian microRNAs: a small world for fine-tuning gene expression [J]. Mamm Genome 2006;17(3):189-202.
18. Zhang B, Wang Q, Pan X. MicroRNAs and their regulatory roles in animals and plants [J]. J Cell Physiol. 2007;210(2):279-289.
19. Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T. Identification of novel genes coding for small expressed RNAs [J]. Science.2001; 294(5543): 853–858.
20. Lau NC, Lim LP, Weinstein EG, Bartel DP. An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans [J]. Science.2001; 294(5543): 858–862.
21. Lee RC, Ambros V. An extensive class of small RNAs in Caenorhabditis elegans [J]. Science. 2001;294(5543): 862–864.
22. Kedde M, Strasser MJ, Boldajipour B, Oude Vrielink JA, Slanchev K, le Sage C, Nagel R, Voorhoeve PM, van Duijse J, ?rom UA, Lund AH, Perrakis A, Raz E,Agami R. RNA-Binding Protein Dnd1 Inhibits MicroRNA Access to Target mRNA [J]. Cell. 2007;131(7):1273-1286.
23. Culjkovic B, Topisirovic I, Skrabanek L, Ruiz-Gutierrez M, Borden KL. eIF4E is a central node of an RNA regulon that governs cellular proliferation [J]. J Cell Biol. 2006;175(3):415-426.
24. Larsson O, Perlman DM, Fan D, Reilly CS, Peterson M, Dahlgren C, Liang Z, Li S, Polunovsky VA, Wahlestedt C, Bitterman PB. Apoptosis resistance downstream of EIF4E: posttranscriptional activation of an anti-apoptotic transcript carrying a consensus hairpin structure [J]. Nucleic Acids Res. 2006;34(16):4375-4386.
25. Eulalio A, Huntzinger E, Izaurralde E. GW182 interaction with Argonaute is essential for miRNA-mediated translational repression and mRNA decay [J]. Nat Struct Mol Biol. 2008;15(4):346-353.
26. López de Silanes I, Zhan M, Lal A, Yang X, Gorospe M. Identification of a target RNA motif for RNA-binding protein HuR [J]. Proc Natl Acad Sci U S A. 2004;101(9):2987-2992.
27. Bhattacharyya SN, Habermacher R, Martine U, Closs EI, Filipowicz W. Relief of microRNA-mediated translational repression in human cells subjected to stress [J]. Cell. 2006;125(6):1111-1124.
28. Vasudevan S, Tong Y, Steitz JA. Switching from repression to activation: microRNAs can up-regulate translation [J]. Science.2007; 318(5858), 1931–1934.
29. Iorio MV, Ferracin M, Liu CG, Veronese A, Spizzo R, Sabbioni S, Magri E, Pedriali M, Fabbri M, Campiglio M, Ménard S, Palazzo JP, Rosenberg A, Musiani P, Volinia S, Nenci I, Calin GA, Querzoli P, Negrini M, Croce CM.MicroRNA Gene Expression Deregulation in Human Breast Cancer [J]. Cancer Res. 2005;65(16):7065-7070.
30. Tavazoie SF, Alarcón C, Oskarsson T, Padua D, Wang Q, Bos PD, Gerald WL, MassaguéJ. Endogenous human microRNAs that suppress breast cancer metastasislet-7 Regulates Self Renewal and Tumorigenicity of Breast Cancer Cell let-7 Regulates Self Renewal and Tumorigenicity of Breast Cancer Cell [J]. Nature. 2008;451(7175):147-152.
31. Yu F, Yao H, Zhu P, Zhang X, Pan Q, Gong C, Huang Y, Hu X, Su F, Lieberman J, Song E. let-7 Regulates Self Renewal and Tumorigenicity of Breast Cancer Cells [J]. Cell. 2007; 131(6):1109-1123.
32. Gregory PA, Bert AG, Paterson EL, Barry SC, Tsykin A, Farshid G, Vadas MA, Khew-Goodall Y, Goodall GJ. The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1 [J]. Nat Cell Biol. 2008;10(5):593-601.
33. Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, Visone R, Iorio M, Roldo C, Ferracin M, Prueitt RL, Yanaihara N, Lanza G, Scarpa A, Vecchione A, Negrini M, Harris CC, Croce CM. A microRNA expression signature of human solid tumors defines cancer gene targets [J]. Proc Natl Acad Sci U S A. 2006;103(7):2257-2261.
34. Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, Downing JR, Jacks T, Horvitz HR, Golub TR. MicroRNA expression profiles classify human cancers [J]. Nature. 2005; 435 (7043):834-838.
35. Hossain A, Kuo MT, Saunders GF. Mir-17-5p regulates breast cancer cell proliferation by inhibiting translation of AIB1 mRNA [J]. Mol Cell Biol. 2006;26(21):8191-8201.
36. http://www.sirna.cn/mirna.aspx
37.张辉,苏式兵,周钱梅,陆亦宇.乳腺癌细胞与乳腺上皮细胞MicroRNAs表达谱的差异性分析[J].癌症, 2009, 28 (5):493-499.
38. Shen J, Ambrosone CB, Zhao H. Novel genetic variants in microRNA genes and familial breast cancer [J]. Int J Cancer. 2009;124(5):1178-1182.
39. Lu Z, Liu M, Stribinskis V, Klinge CM, Ramos KS, Colburn NH, Li Y. MicroRNA-21 promotes cell transformation by targeting the programmed cell death 4 gene [J]. Oncogene. 2008;27(31):4373-4379.
40. Frankel LB, Christoffersen NR, Jacobsen A, Lindow M, Krogh A, Lund AH. Programmed Cell Death 4 (PDCD4) Is an Important Functional Target of the MicroRNA miR-21 in Breast Cancer Cells [J]. J Biol Chem. 2008;283(2):1026-1033.
41. Yu Z, Wang C, Wang M, Li Z, Casimiro MC, Liu M, Wu K, Whittle J, Ju X, Hyslop T, McCue P, Pestell RG.. A cyclin D1/microRNA 17/20 regulatory feedback loop in control of breast cancer cell proliferation [J]. J Cell Biol. 2008; 182(3): 509–517.
42. O'Donnell KA, Wentzel EA, Zeller KI, Dang CV, Mendell JT. c-Myc-regulated microRNAs modulate E2F1 expression [J]. Nature. 2005;435(7043):839-843.
43. Negrini M, Calin GA. Breast cancer metastasis: a microRNA story [J]. Breast Cancer Res. 2008;10(2):203.
44. Yan LX, Huang XF, Shao Q, Huang MY, Deng L, Wu QL, Zeng YX, Shao JY.MicroRNA miR-21 overexpression in human breast cancer is associated with advanced clinical stage, lymph node metastasis and patient poor prognosis [J]. RNA. 2008;14(11):2348-2360.
45. Zhu S, Wu H, Wu F, Nie D, Sheng S, Mo YY. MicroRNA-21 targets tumor suppressor genes in invasion and metastasis [J]. Cell Res.2008;18(3):350-359.
46. Scott GK, Goga A, Bhaumik D, Berger CE, Sullivan CS, Benz CC. Coordinate suppression of ERBB2 and ERBB3 by enforced expression of micro-RNA miR-125a or miR-125b [J]. J Biol Chem. 2007;282(2):1479-1486.
47. Zhu S, Si ML, Wu H, Mo YY. MicroRNA-21 targets the tumor suppressor gene Tropomyosin 1(TPM1) [J]. J Biol Chem. 2007; 282(19):14328-14336.
48. Sempere LF, Christensen M, Silahtaroglu A, Bak M, Heath CV, Schwartz G, Wells W, Kauppinen S, Cole CN. Altered MicroRNA Expression Confined to SpecificEpithelial Cell Subpopulations in Breast Cancer [J]. Cancer Res. 2007;67(24):11612-11620.
49. Foekens JA, Sieuwerts AM, Smid M, Look MP, de Weerd V, Boersma AW, Klijn JG, Wiemer EA, Martens JW. Four miRNAs associated with aggressiveness of lymph node-negative, estrogen receptor-positive human breast cancer [J]. Proc Natl Acad Sci U S A. 2008;105(35):13021-13026.
50. Ma L, Teruya-Feldstein J, Weinberg RA. Tumour invasion and metastasis initiated by microRNA-10b in breast cancer [J]. Nature. 2007;449(7163):682-688.
51. Reddy SD, Ohshiro K, Rayala SK, Kumar R. MicroRNA-7, a homeobox D10 target, inhibits p21-activated kinase 1 and regulates its functions. Cancer Res. 2008;68(20):8195-8200.
52. Camps C, Buffa FM, Colella S, Moore J, Sotiriou C, Sheldon H, Harris AL, Gleadle JM, Ragoussis J. hsa-miR-210 Is Induced by Hypoxia and Is an Independent Prognostic Factor in Breast Cancer [J]. Clin Cancer Res.2008; 14(5):1340-1348.