PT  - JOURNAL ARTICLE
AU  - Ye, Gang
AU  - Fu, Guodong
AU  - Cui, Shiying
AU  - Zhao, Sufen
AU  - Bernaudo, Stefanie
AU  - Bai, Yin
AU  - Ding, Yanfang
AU  - Zhang, Yaou
AU  - Yang, Burton B.
AU  - Peng, Chun
TI  - MicroRNA 376c enhances ovarian cancer cell survival by targeting activin receptor-like kinase 7: implications for chemoresistance
AID  - 10.1242/jcs.072223
DP  - 2011 Feb 01
TA  - Journal of Cell Science
PG  - 359--368
VI  - 124
IP  - 3
4099  - http://jcs.biologists.org/content/124/3/359.short
4100  - http://jcs.biologists.org/content/124/3/359.full
SO  - J. Cell Sci.2011 Feb 01; 124
AB  - MicroRNAs (miRNAs) are small noncoding RNAs that have important roles in gene regulation. We have previously reported that activin receptor-like kinase 7 (ALK7) and its ligand, Nodal, induce apoptosis in human epithelial ovarian cancer cells. In this study, we examined the regulation of ALK7 by miRNAs and demonstrate that miR-376c targets ALK7. Ectopic expression of miR-376c significantly increased cell proliferation and survival, enhanced spheroid formation and blocked Nodal-induced apoptosis. Interestingly, overexpression of miR-376c blocked cisplatin-induced cell death, whereas anti-miR-376c enhanced the effect of cisplatin. These effects of miR-376c were partially compensated by the overexpression of ALK7. Moreover, in serous carcinoma samples taken from ovarian cancer patients who responded well to chemotherapy, strong ALK7 staining and low miR-376c expression was detected. By contrast, ALK7 expression was weak and miR-376c levels were high in samples from patients who responded poorly to chemotherapy. Finally, treatment with cisplatin led to an increase in expression of mRNA encoding Nodal and ALK7 but a decrease in miR-376c levels. Taken together, these results demonstrate that the Nodal–ALK7 pathway is involved in cisplatin-induced cell death in ovarian cancer cells and that miR-376c enhances proliferation, survival and chemoresistance by targeting, at least in part, ALK7.