HOX基因与妇科肿瘤的研究进展
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摘要
同源盒(Homeobox,HOX)基因是一类特殊的转录调节因子,不仅在胚胎发育、细胞生长、分化、迁移等生理性调节机制中起到重要作用,近年来的研究发现,HOX基因表达异常也影响着肿瘤的发生发展。本文主要综述了HOX基因与妇科肿瘤的研究进展,并且阐述了HOX基因在癌症治疗中的指导与应用。期待通过总结现有的研究报道,能够指导在HOX基因方向的探索,从而缓解妇科肿瘤患者的病痛。
The homeobox( HOX) gene is a special type of transcriptional regulator that plays an important role in physiological regulation mechanisms such as embryonic development,cell growth,differentiation and migration. Recent studies have found that HOX gene expression is abnormal and affects the occurrence and development of tumor. This review summarizes the progress of HOX gene and gynecologic oncology including cervical cancer,endometrial cancer and ovarian cancer,and the instruction and application of HOX gene in the treatment of cancer. We are making the guiding direction of exploring HOX gene through summarizing the existed research reports in order to alleviate the pain of gynecological cancer patients.
The homeobox( HOX) gene is a special type of transcriptional regulator that plays an important role in physiological regulation mechanisms such as embryonic development,cell growth,differentiation and migration. Recent studies have found that HOX gene expression is abnormal and affects the occurrence and development of tumor. This review summarizes the progress of HOX gene and gynecologic oncology including cervical cancer,endometrial cancer and ovarian cancer,and the instruction and application of HOX gene in the treatment of cancer. We are making the guiding direction of exploring HOX gene through summarizing the existed research reports in order to alleviate the pain of gynecological cancer patients.
引文
1 Deschamps J,Duboule D.Embryonic timing,axial stem cells,chromatin dynamics,and the Hox clock[J].Genes Dev,2017,31(14):1406-1416.
2 Rux DR,Wellik DM.Hox genes in the adult skeleton:novel functions beyond embryonic development[J].Dev Dyn,2017,246(4):310-317.
3 Platais C,Hakami F,Darda L,et al.The role of HOX genes in head and neck squamous cell carcinoma[J].J Oral Pathol Med,2016,45(4):239-247.
4 Bhatlekar S,Fields JZ,Boman BM.HOX genes and their role in the development of human cancers[J].J Mol Med(Berl),2014,92(8):811-823.
5 Jin WK,Ji YK,Kim JE,et al.HOXA10 is associated with temozolomide resistance through regulation of the homologous recombinant DNA repair pathway in glioblastoma cell lines[J].Genes Cancer,2014,5(5/6):165-174.
6 Darda L,Hakami F,Morgan R,et al.The role of HOXB9and mi R-196a in head and neck squamous cell carcinoma[J].PLo S One,2015,10(4):e0122285.
7 Visconti RP,Awgulewitsch A.Topographic patterns of vascular disease:HOX proteins as determining factors?[J].World J Biol Chem,2015,6(3):65-70.
8 Chang SL,Chan TC,Chen TJ,et al.HOXC6 overexpression is associated with Ki-67 expression and poor survival in NPC patients[J].J Cancer,2017,8(9):1647-1654.
9 Piérard GE,Piérardfranchimont C.HOX gene aberrant expression in skin melanoma:a review[J].J Skin Cancer,2012,2012(24):707260.
10 Luo Z,Rhie SK,Lay FD,et al.A prostate cancer risk element functions as a repressive loop that regulates HOXA13[J].Cell Rep,2017,21(6):1411-1417.
11 Jin K,Sukumar S.HOX genes:Major actors in resistance to selective endocrine response modifiers[J].Biochim Biophys Acta,2016,1865(2):105-110.
12 Kelly Z,Moller-Levet C,Mcgrath S,et al.The prognostic significance of specific HOX gene expression patterns in ovarian cancer[J].Int J Cancer,2016,139(7):1608-1617.
13 Tsuboi M,Taniuchi K,Shimizu T,et al.The transcription factor HOXB7 regulates ERK kinase activity and thereby stimulates the motility and invasiveness of pancreatic cancer cells[J].J Biol Chem,2017,292(43):17681-17702.
14 Marcinkiewicz KM,Gudas LJ.Altered epigenetic regulation of homeobox genes in human oral squamous cell carcinoma cells[J].Exp Cell Res,2014,320(1):128-143.
15 Marcinkiewicz KM,Gudas LJ.Altered histone mark deposition and DNA methylation at homeobox genes in human oral squamous cell carcinoma[J].J Cell Physiol,2014,229(10):1405-1416.
16 Van de Wall S,Nijman HW,Daemen T.HPV-specific immunotherapy:key role for immunomodulators[J].Anticancer Agents Med Chem,2014,14(2):265-279.
17 Alvarado-Ruiz L,Martinez-Silva MG,Torres-Reyes LA,et al.HOXA9 is underexpressed in cervical cancer cells and its restoration decreases proliferation,migration and expression of epithelial-to-mesenchymal transition genes[J].Asian Pac J Cancer Prev,2016,17(3):1037-1047.
18 Sun X,Liu B,Ji W,et al.The role of HOXA9 in human laryngeal squamous cell carcinoma[J].Oncol Res,2013,20(10):467-472.
19 Gonzalez-Herrera A,Salgado-Bernabe M,VelazquezVelazquez C,et al.Increased expression of HOXB2 and HOXB13 proteins is associated with HPV infection and cervical cancer progression[J].Asian Pac J Cancer Prev,2015,16(4):1349-1353.
20 Saha SS,Chowdhury RR,Mondal NR,et al.Expression signatures of HOX cluster genes in cervical cancer pathogenesis:Impact of human papillomavirus type 16 oncoprotein E7[J].Oncotarget,2017,8(22):36591-36602.
21 Zhang HY,Li JH,Li G,et al.Activation of ARK5/mi R-1181/HOXA10 axis promotes epithelial-mesenchymal transition in ovarian cancer[J].Oncol Rep,2015,34(3):1193-1202.
22 Yuan H,Kajiyama H,Ito S,et al.HOXB13 and ALX4 induce SLUG expression for the promotion of EMT and cell invasion in ovarian cancer cells[J].Oncotarget,2015,6(15):13359-13370.
23 Zhai LL,Wu Y,Cai CY,et al.Overexpression of homeobox B-13 correlates with angiogenesis,aberrant expression of EMT markers,aggressive characteristics and poor prognosis in pancreatic carcinoma[J].Int J Clin Exp Pathol,2015,8(6):6919-6927.
24 Zhang L,Wan Y,Jiang Y,et al.Upregulation HOXA10 homeobox gene in endometrial cancer:role in cell cycle regulation[J].Med Oncol,2014,31(7):52.
25 Chen J,Yao Y,Gong C,et al.CCL18 from tumor-associated macrophages promotes breast cancer metastasis via PITPNM3[J].Cancer Cell,2011,19(4):541-555.
26 Wen Z,Liu H,Li M,et al.Increased metabolites of 5-lipoxygenase from hypoxic ovarian cancer cells promote tumor-associated macrophage infiltration[J].Oncogene,2015,34(10):1241-1252.
27 Kübler K,Ayub TH,Weber SK,et al.Prognostic significance of tumor-associated macrophages in endometrial adenocarcinoma[J].Gynecol Oncol,2014,135(2):176-183.
28 Wang J,Cao Z,Zhang XM,et al.Novel mechanism of macrophage-mediated metastasis revealed in a zebrafish model of tumor development[J].Cancer Res,2015,75(2):306-315.
29 Tong H,Ke JQ,Jiang FZ,et al.Tumor-associated macrophage-derived CXCL8 could induce ERαsuppression via HOXB13 in endometrial cancer[J].Cancer Lett,2016,376(1):127-136.
30 Ko SY,Naora H.HOXA9 promotes homotypic and heterotypic cell interactions that facilitate ovarian cancer dissemination via its induction of P-cadherin[J].Mol Cancer,2014,13(1):170.
31 Ko S-Y,Naora H.Adaptation of ovarian cancer cells to the peritoneal environment:Multiple mechanisms of the developmental patterning gene HOXA9[J].Cancer Cell Microenviron,2014,1(6):e379.
32 Miller KR,Patel JN,Ganapathi MK,et al.Biological role and clinical implications of homeobox genes in serous epithelial ovarian cancer[J].Gynecol Oncol,2016,141(3):608-615.
33 Kelly Z,Moller-Levet C,Mcgrath S,et al.The prognostic significance of specific HOX gene expression patterns in ovarian cancer[J].Int J Cancer,2016,139(7):1608-1617.
34 Lu S,Liu R,Su M,et al.Overexpression of HOXC8 is associated with poor prognosis in epithelial ovarian cancer[J].Reprod Sci,2016,23(7):944-954.
35 Tait DL,Bahrani-Mostafavi Z,Vestal CG,et al.Downregulation of HOXC6 in serous ovarian cancer[J].Cancer Invest,2015,33(7):303-311.
36 Jin K,Kong X,Shah T,et al.The HOXB7 protein renders breast cancer cells resistant to tamoxifen through activation of the EGFR pathway[J].Proc Natl Acad Sci U S A,2012,109(8):2736-2741.
37 Kelly Z,Moller-Levet C,Mcgrath S,et al.The prognostic significance of specific HOX gene expression patterns in ovarian cancer[J].Int J Cancer,2016,139(7):1608-1617.
38 Xiao F,Bai Y,Chen Z,et al.Downregulation of HOXA1gene affects small cell lung cancer cell survival and chemoresistance under the regulation of mi R-100[J].Eur J Cancer,2014,50(8):1541-1554.
2 Rux DR,Wellik DM.Hox genes in the adult skeleton:novel functions beyond embryonic development[J].Dev Dyn,2017,246(4):310-317.
3 Platais C,Hakami F,Darda L,et al.The role of HOX genes in head and neck squamous cell carcinoma[J].J Oral Pathol Med,2016,45(4):239-247.
4 Bhatlekar S,Fields JZ,Boman BM.HOX genes and their role in the development of human cancers[J].J Mol Med(Berl),2014,92(8):811-823.
5 Jin WK,Ji YK,Kim JE,et al.HOXA10 is associated with temozolomide resistance through regulation of the homologous recombinant DNA repair pathway in glioblastoma cell lines[J].Genes Cancer,2014,5(5/6):165-174.
6 Darda L,Hakami F,Morgan R,et al.The role of HOXB9and mi R-196a in head and neck squamous cell carcinoma[J].PLo S One,2015,10(4):e0122285.
7 Visconti RP,Awgulewitsch A.Topographic patterns of vascular disease:HOX proteins as determining factors?[J].World J Biol Chem,2015,6(3):65-70.
8 Chang SL,Chan TC,Chen TJ,et al.HOXC6 overexpression is associated with Ki-67 expression and poor survival in NPC patients[J].J Cancer,2017,8(9):1647-1654.
9 Piérard GE,Piérardfranchimont C.HOX gene aberrant expression in skin melanoma:a review[J].J Skin Cancer,2012,2012(24):707260.
10 Luo Z,Rhie SK,Lay FD,et al.A prostate cancer risk element functions as a repressive loop that regulates HOXA13[J].Cell Rep,2017,21(6):1411-1417.
11 Jin K,Sukumar S.HOX genes:Major actors in resistance to selective endocrine response modifiers[J].Biochim Biophys Acta,2016,1865(2):105-110.
12 Kelly Z,Moller-Levet C,Mcgrath S,et al.The prognostic significance of specific HOX gene expression patterns in ovarian cancer[J].Int J Cancer,2016,139(7):1608-1617.
13 Tsuboi M,Taniuchi K,Shimizu T,et al.The transcription factor HOXB7 regulates ERK kinase activity and thereby stimulates the motility and invasiveness of pancreatic cancer cells[J].J Biol Chem,2017,292(43):17681-17702.
14 Marcinkiewicz KM,Gudas LJ.Altered epigenetic regulation of homeobox genes in human oral squamous cell carcinoma cells[J].Exp Cell Res,2014,320(1):128-143.
15 Marcinkiewicz KM,Gudas LJ.Altered histone mark deposition and DNA methylation at homeobox genes in human oral squamous cell carcinoma[J].J Cell Physiol,2014,229(10):1405-1416.
16 Van de Wall S,Nijman HW,Daemen T.HPV-specific immunotherapy:key role for immunomodulators[J].Anticancer Agents Med Chem,2014,14(2):265-279.
17 Alvarado-Ruiz L,Martinez-Silva MG,Torres-Reyes LA,et al.HOXA9 is underexpressed in cervical cancer cells and its restoration decreases proliferation,migration and expression of epithelial-to-mesenchymal transition genes[J].Asian Pac J Cancer Prev,2016,17(3):1037-1047.
18 Sun X,Liu B,Ji W,et al.The role of HOXA9 in human laryngeal squamous cell carcinoma[J].Oncol Res,2013,20(10):467-472.
19 Gonzalez-Herrera A,Salgado-Bernabe M,VelazquezVelazquez C,et al.Increased expression of HOXB2 and HOXB13 proteins is associated with HPV infection and cervical cancer progression[J].Asian Pac J Cancer Prev,2015,16(4):1349-1353.
20 Saha SS,Chowdhury RR,Mondal NR,et al.Expression signatures of HOX cluster genes in cervical cancer pathogenesis:Impact of human papillomavirus type 16 oncoprotein E7[J].Oncotarget,2017,8(22):36591-36602.
21 Zhang HY,Li JH,Li G,et al.Activation of ARK5/mi R-1181/HOXA10 axis promotes epithelial-mesenchymal transition in ovarian cancer[J].Oncol Rep,2015,34(3):1193-1202.
22 Yuan H,Kajiyama H,Ito S,et al.HOXB13 and ALX4 induce SLUG expression for the promotion of EMT and cell invasion in ovarian cancer cells[J].Oncotarget,2015,6(15):13359-13370.
23 Zhai LL,Wu Y,Cai CY,et al.Overexpression of homeobox B-13 correlates with angiogenesis,aberrant expression of EMT markers,aggressive characteristics and poor prognosis in pancreatic carcinoma[J].Int J Clin Exp Pathol,2015,8(6):6919-6927.
24 Zhang L,Wan Y,Jiang Y,et al.Upregulation HOXA10 homeobox gene in endometrial cancer:role in cell cycle regulation[J].Med Oncol,2014,31(7):52.
25 Chen J,Yao Y,Gong C,et al.CCL18 from tumor-associated macrophages promotes breast cancer metastasis via PITPNM3[J].Cancer Cell,2011,19(4):541-555.
26 Wen Z,Liu H,Li M,et al.Increased metabolites of 5-lipoxygenase from hypoxic ovarian cancer cells promote tumor-associated macrophage infiltration[J].Oncogene,2015,34(10):1241-1252.
27 Kübler K,Ayub TH,Weber SK,et al.Prognostic significance of tumor-associated macrophages in endometrial adenocarcinoma[J].Gynecol Oncol,2014,135(2):176-183.
28 Wang J,Cao Z,Zhang XM,et al.Novel mechanism of macrophage-mediated metastasis revealed in a zebrafish model of tumor development[J].Cancer Res,2015,75(2):306-315.
29 Tong H,Ke JQ,Jiang FZ,et al.Tumor-associated macrophage-derived CXCL8 could induce ERαsuppression via HOXB13 in endometrial cancer[J].Cancer Lett,2016,376(1):127-136.
30 Ko SY,Naora H.HOXA9 promotes homotypic and heterotypic cell interactions that facilitate ovarian cancer dissemination via its induction of P-cadherin[J].Mol Cancer,2014,13(1):170.
31 Ko S-Y,Naora H.Adaptation of ovarian cancer cells to the peritoneal environment:Multiple mechanisms of the developmental patterning gene HOXA9[J].Cancer Cell Microenviron,2014,1(6):e379.
32 Miller KR,Patel JN,Ganapathi MK,et al.Biological role and clinical implications of homeobox genes in serous epithelial ovarian cancer[J].Gynecol Oncol,2016,141(3):608-615.
33 Kelly Z,Moller-Levet C,Mcgrath S,et al.The prognostic significance of specific HOX gene expression patterns in ovarian cancer[J].Int J Cancer,2016,139(7):1608-1617.
34 Lu S,Liu R,Su M,et al.Overexpression of HOXC8 is associated with poor prognosis in epithelial ovarian cancer[J].Reprod Sci,2016,23(7):944-954.
35 Tait DL,Bahrani-Mostafavi Z,Vestal CG,et al.Downregulation of HOXC6 in serous ovarian cancer[J].Cancer Invest,2015,33(7):303-311.
36 Jin K,Kong X,Shah T,et al.The HOXB7 protein renders breast cancer cells resistant to tamoxifen through activation of the EGFR pathway[J].Proc Natl Acad Sci U S A,2012,109(8):2736-2741.
37 Kelly Z,Moller-Levet C,Mcgrath S,et al.The prognostic significance of specific HOX gene expression patterns in ovarian cancer[J].Int J Cancer,2016,139(7):1608-1617.
38 Xiao F,Bai Y,Chen Z,et al.Downregulation of HOXA1gene affects small cell lung cancer cell survival and chemoresistance under the regulation of mi R-100[J].Eur J Cancer,2014,50(8):1541-1554.