卵巢癌中E2F1通过影响miR-106b-5P调节RhoC的表达
|
摘要
目的探讨卵巢癌中E2F1、miR-106b-5P以及RhoC三者的表达的关系。方法使用Spearman相关分析方法分析卵巢癌组织中E2F1和miR-106b-5P表达水平的相关关系;OVCAR3和A2780细胞中转染或沉默E2F1,通过RT-PCR检测miR-106b-5P和RhoC的表达,转染miR-106b-5P后检测RhoC的表达。结果经分析发现卵巢癌组织中E2F1和miR-106b-5P表达水平呈负相关。卵巢癌细胞转染E2F1后miR-106b-5P表达水平下降,RhoC的表达水平上升;转染si-E2F1后结果相反;而在卵巢癌细胞中转染miR-106b-5P后发现RhoC的表达水平下降。结论 E2F1负调控miR-106b-5P表达调控RhoC的表达。
Objective To investigate the relationship between expressions of E2F1, miR-106b-5P and RhoC in ovarian cancer. Methods Spearman correlation analysis was used to analyze the expressions of E2F1 and miR-106b-5P in ovarian cancer. After E2F1 overexpression or downregulation in OVCAR3 and A2780 ovarian cancer cells, the expression of E2F1, miR-106b-5P and RhoC was detected by RT-PCR. The expression of RhoC was detected after transfection with miR-106b-5P. Results The expression levels of E2F1 and miR-106b-5P in OVCAR3 and A2780 cells were negatively correlated. The expression level of miR-106b-5P was decreased and the expression level of RhoC was increased after E2F1 was transfected into OVCAR3 or A2780 cells, but the results were reversed after E2F1 downregulation; the expression levelof RhoC was decreased after miR-106b-5P overexpression in OVCAR3 or A2780 cells. Conclusion E2F1 regulates the expression of RhoC via negative regulation of miR-106b-5P.
Objective To investigate the relationship between expressions of E2F1, miR-106b-5P and RhoC in ovarian cancer. Methods Spearman correlation analysis was used to analyze the expressions of E2F1 and miR-106b-5P in ovarian cancer. After E2F1 overexpression or downregulation in OVCAR3 and A2780 ovarian cancer cells, the expression of E2F1, miR-106b-5P and RhoC was detected by RT-PCR. The expression of RhoC was detected after transfection with miR-106b-5P. Results The expression levels of E2F1 and miR-106b-5P in OVCAR3 and A2780 cells were negatively correlated. The expression level of miR-106b-5P was decreased and the expression level of RhoC was increased after E2F1 was transfected into OVCAR3 or A2780 cells, but the results were reversed after E2F1 downregulation; the expression levelof RhoC was decreased after miR-106b-5P overexpression in OVCAR3 or A2780 cells. Conclusion E2F1 regulates the expression of RhoC via negative regulation of miR-106b-5P.
引文
[1].Loessner D,Little JP,Pettet GJ,et al.A multiscale road map of cancer spheroids--incorporating experimental and mathematical modelling to understand cancer progression[J].J Cell Sci,2013,126(Pt 13):2761-2771.
[2].Hall M,Gourley C,Mc Neish I,et al.Targeted anti-vascular therapies for ovarian cancer:current evidence[J].Br J Cancer,2013,108(2):250-258.
[3]Meng P,Ghosh R.Transcription addiction:can we garner the Yin and Yang functions of E2F1 forcancer therapy[J].Cell Death Dis,2014,5:e1360.
[4]Engelmann D,Pützer BM.The dark side of E2F1:in transit beyond apoptosis[J].Cancer Res,2012,72(3):571-575.
[5]Shi C,Huang F,Gu X,et al.Adipogenic mi RNA and meta-signature mi RNAs involved in human adipocyte differentiation and obesity[J].Oncotarget,2016,7(26):40830-40845.
[6].Rupaimoole R,Calin GA,Lopez-Berestein G,et al.mi RNAderegulation in cancer cells and the tumor microenvironment[J].Cancer Discov,2016,6(3):235-246.
[7].Croft DR,Crighton D,Samuel MS,et al.p53-mediated transcriptional regulation and activation of the actin cytoskeleton regulatory Rho C to LIMK2 signaling pathway promotes cell survival[J].Cell Res,2011,21(4):666-682.
[8]Vega FM,Fruhwirth G,Ng T,et al.Rho A and Rho C have distinct roles in migration and invasion by acting through different targets[J].J Cell Biol,2011,193(4):655-665.
[9].Bravo-Cordero JJ,Hodgson L,Condeelis JS.Spatial regulation of tumor cell protrusions by Rho C[J].Cell Adh Migr,2014,8(3):263-267.
[10]Chen S,Chen X,Xiu YL,et al.Inhibition of ovarian epithelial carcinoma tumorigenesis and progression by micro RNA 106b mediated through the Rho C pathway[J].PLo S One,2015,10(5):e0125714.
[11]Sang XB,Zong ZH,Wang LL,et al.E2F-1 targets mi R-519d to regulate the expression of the ras homolog gene family member C[J].Oncotarget,2017,doi:10.18632/oncotarget.14833.
[12]Choiniere JP,Wu J,Wang L.PDK4-deficiency results in expedited cellular proliferation through E2F1-mediated increase of cyclins[J].Mol Pharmacol,2016,91(3):189-196.
[13].Yang S,Wu B,Sun H,et al.Interrupted E2F1-mi R-34c-SCFnegative feedback loop by hyper-methylation promotes colorectal cancer cell proliferation[J].Biosci Rep,2015,36(1):e00293.
[14].Zhan W,Wang W,Han T,et al.COMMD9 promotes TFDP1/E2F1 transcriptional activity via interaction with TFDP1 in non-small cell lung cancer[J].Cell Signal,2017,30:59-66.
[15]Cataldo A,Cheung DG,Balsari A,et al.mi R-302b enhances breast cancer cell sensitivity to cisplatin by regulating E2F1 and the cellular DNA damage response[J].Oncotarget,2016,7(1):786-797.
[16]Yan LH,Chen ZN,Li L,et al.mi R-135a promotes gastric cancer progression and resistance to oxaliplatin[J].Oncotarget,2016,7(43):70699-70714.
[17].Luo W,Li G,Yi Z,et al.E2F1-mi R-20a-5p/20b-5p autoregulatory feedback loop involved in myoblast proliferation and differentiation[J].Sci Rep,2016,6:27904.
[18].Liu Z,Cheng C,Luo X,et al.CDK4 and mi R-15a comprise an abnormal automodulatory feedback loop stimulating the pathogenesis and inducing chemotherapy resistance in nasopharyngeal carcinoma[J].BMC Cancer,2016,16:238.
[19]Verboon LJ,Obulkasim A,de Rooij JD,et al.Micro RNA-106b~25cluster is upregulated in relapsed MLL-rearranged pediatric acute myeloid leukemia[J].Oncotarget,2016,7(30):48412-48422.
[2].Hall M,Gourley C,Mc Neish I,et al.Targeted anti-vascular therapies for ovarian cancer:current evidence[J].Br J Cancer,2013,108(2):250-258.
[3]Meng P,Ghosh R.Transcription addiction:can we garner the Yin and Yang functions of E2F1 forcancer therapy[J].Cell Death Dis,2014,5:e1360.
[4]Engelmann D,Pützer BM.The dark side of E2F1:in transit beyond apoptosis[J].Cancer Res,2012,72(3):571-575.
[5]Shi C,Huang F,Gu X,et al.Adipogenic mi RNA and meta-signature mi RNAs involved in human adipocyte differentiation and obesity[J].Oncotarget,2016,7(26):40830-40845.
[6].Rupaimoole R,Calin GA,Lopez-Berestein G,et al.mi RNAderegulation in cancer cells and the tumor microenvironment[J].Cancer Discov,2016,6(3):235-246.
[7].Croft DR,Crighton D,Samuel MS,et al.p53-mediated transcriptional regulation and activation of the actin cytoskeleton regulatory Rho C to LIMK2 signaling pathway promotes cell survival[J].Cell Res,2011,21(4):666-682.
[8]Vega FM,Fruhwirth G,Ng T,et al.Rho A and Rho C have distinct roles in migration and invasion by acting through different targets[J].J Cell Biol,2011,193(4):655-665.
[9].Bravo-Cordero JJ,Hodgson L,Condeelis JS.Spatial regulation of tumor cell protrusions by Rho C[J].Cell Adh Migr,2014,8(3):263-267.
[10]Chen S,Chen X,Xiu YL,et al.Inhibition of ovarian epithelial carcinoma tumorigenesis and progression by micro RNA 106b mediated through the Rho C pathway[J].PLo S One,2015,10(5):e0125714.
[11]Sang XB,Zong ZH,Wang LL,et al.E2F-1 targets mi R-519d to regulate the expression of the ras homolog gene family member C[J].Oncotarget,2017,doi:10.18632/oncotarget.14833.
[12]Choiniere JP,Wu J,Wang L.PDK4-deficiency results in expedited cellular proliferation through E2F1-mediated increase of cyclins[J].Mol Pharmacol,2016,91(3):189-196.
[13].Yang S,Wu B,Sun H,et al.Interrupted E2F1-mi R-34c-SCFnegative feedback loop by hyper-methylation promotes colorectal cancer cell proliferation[J].Biosci Rep,2015,36(1):e00293.
[14].Zhan W,Wang W,Han T,et al.COMMD9 promotes TFDP1/E2F1 transcriptional activity via interaction with TFDP1 in non-small cell lung cancer[J].Cell Signal,2017,30:59-66.
[15]Cataldo A,Cheung DG,Balsari A,et al.mi R-302b enhances breast cancer cell sensitivity to cisplatin by regulating E2F1 and the cellular DNA damage response[J].Oncotarget,2016,7(1):786-797.
[16]Yan LH,Chen ZN,Li L,et al.mi R-135a promotes gastric cancer progression and resistance to oxaliplatin[J].Oncotarget,2016,7(43):70699-70714.
[17].Luo W,Li G,Yi Z,et al.E2F1-mi R-20a-5p/20b-5p autoregulatory feedback loop involved in myoblast proliferation and differentiation[J].Sci Rep,2016,6:27904.
[18].Liu Z,Cheng C,Luo X,et al.CDK4 and mi R-15a comprise an abnormal automodulatory feedback loop stimulating the pathogenesis and inducing chemotherapy resistance in nasopharyngeal carcinoma[J].BMC Cancer,2016,16:238.
[19]Verboon LJ,Obulkasim A,de Rooij JD,et al.Micro RNA-106b~25cluster is upregulated in relapsed MLL-rearranged pediatric acute myeloid leukemia[J].Oncotarget,2016,7(30):48412-48422.