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微小RNA-630抑制剂通过增强细胞凋亡使化疗耐药的卵巢癌对化疗敏感。

MicroRNA-630 inhibitor sensitizes chemoresistant ovarian cancer to chemotherapy by enhancing apoptosis.

作者信息

Eoh Kyung Jin, Lee So Hyun, Kim Hee Jung, Lee Jung-Yun, Kim Sunghoon, Kim Sang Wun, Kim Young Tae, Nam Eun Ji

机构信息

Department of Obstetrics and Gynecology, Women's Cancer Center, Yonsei Cancer Center, Institute of Women's Life Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea.

Department of Obstetrics and Gynecology, Women's Cancer Center, Yonsei Cancer Center, Institute of Women's Life Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea.

出版信息

Biochem Biophys Res Commun. 2018 Mar 4;497(2):513-520. doi: 10.1016/j.bbrc.2018.02.062. Epub 2018 Feb 13.

Abstract

MicroRNA-630 (miR-630) has been implicated in the development and progression of multiple cancers. The current study aimed to investigate the role of miR-630 in chemoresistant epithelial ovarian cancer. MiR-630 expression levels were detected in ovarian cancer cell line SKOV3 and paclitaxel-resistant SKOV3 (SKOV3-TR) via microarray and qRT-PCR. MiR-630 inhibitors and negative controls were transfected into SKOV3 and SKOV3-TR cells. Wound healing, invasion, chemosensitivity, and cell apoptosis assays were performed to determine proliferation and migration rates. Chemoresistant patient-derived xenograft (PDX) models were established and utilized to verify the effect of miR-630 on chemoresistant ovarian cancer. Inhibition of miR-630 decreased cell proliferation and enhanced the sensitivity of SKOV3-TR and SKOV3 cells to paclitaxel. In the chemosensitivity assay, we observed that the miR-630 inhibitor exhibited a synergistic effect with paclitaxel on SKOV3-TR cells. Inhibition was correlated with enhanced expression of apoptosis-related proteins. APAF-1 was predicted to be a potential target of miR-630. An in vivo PDX study showed that the miR-630 inhibitor sensitized chemoresistant ovarian cancer to paclitaxel. Thus, miR-630 inhibitor sensitizes chemoresistant epithelial ovarian cancer to chemotherapy by enhancing apoptosis. Our findings suggest that miR-630 might be a potential therapeutic target for chemotherapy-resistant ovarian cancer.

摘要

微小RNA-630(miR-630)与多种癌症的发生和发展有关。本研究旨在探讨miR-630在化疗耐药的上皮性卵巢癌中的作用。通过微阵列和qRT-PCR检测卵巢癌细胞系SKOV3和耐紫杉醇的SKOV3(SKOV3-TR)中miR-630的表达水平。将miR-630抑制剂和阴性对照转染到SKOV3和SKOV3-TR细胞中。进行伤口愈合、侵袭、化学敏感性和细胞凋亡检测以确定增殖和迁移率。建立并利用化疗耐药的患者来源异种移植(PDX)模型来验证miR-630对化疗耐药性卵巢癌的作用。抑制miR-630可降低细胞增殖,并增强SKOV3-TR和SKOV3细胞对紫杉醇的敏感性。在化学敏感性检测中,我们观察到miR-630抑制剂与紫杉醇对SKOV3-TR细胞具有协同作用。抑制作用与凋亡相关蛋白表达的增强相关。APAF-1被预测为miR-630的潜在靶点。一项体内PDX研究表明miR-630抑制剂使化疗耐药的卵巢癌对紫杉醇敏感。因此,miR-630抑制剂通过增强凋亡使化疗耐药的上皮性卵巢癌对化疗敏感。我们的研究结果表明,miR-630可能是化疗耐药性卵巢癌的潜在治疗靶点。

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