MicroRNA-10a promotes granulosa cells tumor development / 中国药理学与毒理学杂志

ABSTRACT

OBJECTIVE To investigate the effect of microRNA-10a on the development of granulosa cells tumor (GCT). METHODS FISH 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 wereconstructed 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. RESULTS Strong 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. CONCLUSION Taken together, our results demonstrate that the miR-10a is positively involved in development of GCT.