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miR-146a Inhibits Proliferation and Enhances Chemosensitivity in Epithelial Ovarian Cancer via Reduction of SOD2.
Oncol Res. 2016 May; 23(6):275-282.OR

Abstract

Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy, accounting for 90% of all ovarian cancer. Dysregulation of miRNAs is associated with several types of EOC. In the current research, we aimed to study the role of abnormal expression of miR-146a in the development of EOC and to elucidate the possible molecular mechanisms. Compared with control samples, mRNA expression of miR-146a was significantly decreased in EOC tissues and cell lines. Overexpression of miR-146a prohibited cell proliferation, enhanced apoptosis, and increased sensitivity to chemotherapy drugs in EOC cells. In contrast, downregulation of miR-146a promoted cell proliferation, suppressed apoptosis, and decreased sensitivity to chemotherapy drugs in EOC cells. Overexpression of miR-146a increased the reactive oxygen species (ROS) level and decreased SOD2 mRNA and protein expression. Downregulation of miR-146a increased SOD2 mRNA and protein expression. Overexpression of SOD2 significantly inhibited miR-146a mimics-induced suppression of cell proliferation and the increase of apoptosis and chemosensitivity. In conclusion, we identify miR-146a as a potential tumor suppressor in patients with EOC. miR-146a downregulates the expression of SOD2 and enhances ROS generation, leading to increased apoptosis, inhibition of proliferation, and enhanced sensitivity to chemotherapy. The data demonstrate that the miR-146a/SOD2/ROS pathway may serve as a novel therapeutic target and prognostic marker in patients with EOC.

Authors+Show Affiliations

Department of Obstetrics and Gynecology, Xijing Hospital, Fourth Military Medical University, Xian, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27931283

Citation

Cui, YaJie, et al. "MiR-146a Inhibits Proliferation and Enhances Chemosensitivity in Epithelial Ovarian Cancer Via Reduction of SOD2." Oncology Research, vol. 23, no. 6, 2016, pp. 275-282.
Cui Y, She K, Tian D, et al. MiR-146a Inhibits Proliferation and Enhances Chemosensitivity in Epithelial Ovarian Cancer via Reduction of SOD2. Oncol Res. 2016;23(6):275-282.
Cui, Y., She, K., Tian, D., Zhang, P., & Xin, X. (2016). MiR-146a Inhibits Proliferation and Enhances Chemosensitivity in Epithelial Ovarian Cancer via Reduction of SOD2. Oncology Research, 23(6), 275-282.
Cui Y, et al. MiR-146a Inhibits Proliferation and Enhances Chemosensitivity in Epithelial Ovarian Cancer Via Reduction of SOD2. Oncol Res. 2016;23(6):275-282. PubMed PMID: 27931283.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - miR-146a Inhibits Proliferation and Enhances Chemosensitivity in Epithelial Ovarian Cancer via Reduction of SOD2. AU - Cui,YaJie, AU - She,Kaie, AU - Tian,Defu, AU - Zhang,Peilian, AU - Xin,Xiaoyan, PY - 2016/12/10/entrez PY - 2016/12/10/pubmed PY - 2017/1/4/medline SP - 275 EP - 282 JF - Oncology research JO - Oncol. Res. VL - 23 IS - 6 N2 - Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy, accounting for 90% of all ovarian cancer. Dysregulation of miRNAs is associated with several types of EOC. In the current research, we aimed to study the role of abnormal expression of miR-146a in the development of EOC and to elucidate the possible molecular mechanisms. Compared with control samples, mRNA expression of miR-146a was significantly decreased in EOC tissues and cell lines. Overexpression of miR-146a prohibited cell proliferation, enhanced apoptosis, and increased sensitivity to chemotherapy drugs in EOC cells. In contrast, downregulation of miR-146a promoted cell proliferation, suppressed apoptosis, and decreased sensitivity to chemotherapy drugs in EOC cells. Overexpression of miR-146a increased the reactive oxygen species (ROS) level and decreased SOD2 mRNA and protein expression. Downregulation of miR-146a increased SOD2 mRNA and protein expression. Overexpression of SOD2 significantly inhibited miR-146a mimics-induced suppression of cell proliferation and the increase of apoptosis and chemosensitivity. In conclusion, we identify miR-146a as a potential tumor suppressor in patients with EOC. miR-146a downregulates the expression of SOD2 and enhances ROS generation, leading to increased apoptosis, inhibition of proliferation, and enhanced sensitivity to chemotherapy. The data demonstrate that the miR-146a/SOD2/ROS pathway may serve as a novel therapeutic target and prognostic marker in patients with EOC. SN - 1555-3906 UR - https://www.unboundmedicine.com/medline/citation/27931283/miR_146a_Inhibits_Proliferation_and_Enhances_Chemosensitivity_in_Epithelial_Ovarian_Cancer_via_Reduction_of_SOD2_ L2 - https://www.ingentaconnect.com/openurl?genre=article&issn=0965-0407&volume=23&issue=6&spage=275&aulast=Cui DB - PRIME DP - Unbound Medicine ER -