RT Journal Article
SR Electronic
T1 MicroRNA 376c enhances ovarian cancer cell survival by targeting activin receptor-like kinase 7: implications for chemoresistance
JF Journal of Cell Science
JO J. Cell Sci.
FD The Company of Biologists Ltd
SP 359
OP 368
DO 10.1242/jcs.072223
VO 124
IS 3
A1 Ye, Gang
A1 Fu, Guodong
A1 Cui, Shiying
A1 Zhao, Sufen
A1 Bernaudo, Stefanie
A1 Bai, Yin
A1 Ding, Yanfang
A1 Zhang, Yaou
A1 Yang, Burton B.
A1 Peng, Chun
YR 2011
UL http://jcs.biologists.org/content/124/3/359.abstract
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.