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MicroRNA 376c enhances ovarian cancer cell survival by targeting activin receptor-like kinase 7: implications for chemoresistance.
J Cell Sci 2011; 124(Pt 3):359-68JC

Abstract

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.

Authors+Show Affiliations

Department of Biology, York University, 4700 Keel Street, Toronto ONM3J1P3, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21224400

Citation

Ye, Gang, et al. "MicroRNA 376c Enhances Ovarian Cancer Cell Survival By Targeting Activin Receptor-like Kinase 7: Implications for Chemoresistance." Journal of Cell Science, vol. 124, no. Pt 3, 2011, pp. 359-68.
Ye G, Fu G, Cui S, et al. MicroRNA 376c enhances ovarian cancer cell survival by targeting activin receptor-like kinase 7: implications for chemoresistance. J Cell Sci. 2011;124(Pt 3):359-68.
Ye, G., Fu, G., Cui, S., Zhao, S., Bernaudo, S., Bai, Y., ... Peng, C. (2011). MicroRNA 376c enhances ovarian cancer cell survival by targeting activin receptor-like kinase 7: implications for chemoresistance. Journal of Cell Science, 124(Pt 3), pp. 359-68. doi:10.1242/jcs.072223.
Ye G, et al. MicroRNA 376c Enhances Ovarian Cancer Cell Survival By Targeting Activin Receptor-like Kinase 7: Implications for Chemoresistance. J Cell Sci. 2011 Feb 1;124(Pt 3):359-68. PubMed PMID: 21224400.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MicroRNA 376c enhances ovarian cancer cell survival by targeting activin receptor-like kinase 7: implications for chemoresistance. 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, Y1 - 2011/01/11/ PY - 2011/1/13/entrez PY - 2011/1/13/pubmed PY - 2011/8/2/medline SP - 359 EP - 68 JF - Journal of cell science JO - J. Cell. Sci. VL - 124 IS - Pt 3 N2 - 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. SN - 1477-9137 UR - https://www.unboundmedicine.com/medline/citation/21224400/MicroRNA_376c_enhances_ovarian_cancer_cell_survival_by_targeting_activin_receptor_like_kinase_7:_implications_for_chemoresistance_ L2 - http://jcs.biologists.org/cgi/pmidlookup?view=long&pmid=21224400 DB - PRIME DP - Unbound Medicine ER -