MicroRNA-10a promotes granulosa cells tumor development

Jia-jie TU,Wei WEI

(Institute of Clinical Pharmacology,Anhui Medical University,Key Laboratory of Anti-inflammatory and Immune Medicine,Ministry of Education,Anhui Collaborative Innovation Center of Anti-inflammatory and Immune Medicine,Hefei 230032,China)

T1-31

MicroRNA-10a promotes granulosa cells tumor development

Jia-jie TU,Wei WEI

(Institute of Clinical Pharmacology,Anhui Medical University,Key Laboratory of Anti-inflammatory and Immune Medicine,Ministry of Education,Anhui Collaborative Innovation Center of Anti-inflammatory and Immune Medicine,Hefei 230032,China)

OBJECTIVETo investigate the effect of microRNA-10a on the development of granulosa cells tumor(GCT).METHODSFISH was used to detect the miR-10a expression in tissues from GCT patients.Several functional assays were performed to investigate the effect of miR-10a on proliferation,migration,invasion,spheroid formation and repressed anticancer drug-induced apoptosis of GCT in vitro.CRISPR-Cas9 system mediated miR-10a knockout in cancer GC and two mice GCT models were constructed to show the knockdown effect of miR-10a on cancer GC both in vitro and in vivo.RNA-seq,Western blot,luciferase reporter assay and FISH were used to identify potential direct functional targets and related pathways of miR-10a in cancer GC.RESULTSStrong miR-10a signal was detected in tissues from malignant GCT patients.And amplification of miR-10a negatively correlated with overall survival rate of ovarian cancer patients.In addition,ectopic expression of miR-10a significantly promoted cell proliferation,migration,invasion,spheroid formation and repressed anticancer drug-induced apoptosis in vitro.CRISPR-Cas9 system mediated miR-10a knockout in cancer GC showed opposite phenotype compared to miR-10a overexpressed cancer GC.By using xenograft and orthotropic models,the onco?genic role of miR-10a was further confirmed in vivo.RNA-seq,Western blot,luciferase reporter assay and FISH were used to identified PTEN/TET2 as direct functional targets of miR-10a in cancer GC;Akt and Wnt were found as two associated signaling pathways of miR-10a in cancer GC.CONCLUSIONTaken together,our results demonstrate that the miR-10a is positively involved in

development of GCT.

microRNA-10a;granulsoa cells tumor;CRISPR-Cas9;PTEN;TET2;Akt pathway;Wnt pathway

The project supported by Natural Science Foundation of Anhui Province for Young Scholars(1708085QH200)

Jia-jie TU,Tel:13956924508,E-mail：tujiajie@ahme.edu.cn;Wei WEI,Tel:13605510563,E-mail：wwei@ahmu.edu.cn