Department of Oncology, The First People's Hospital of Lianyungang, Lianyungang, China.
Yonsei Med J. 2019 Dec;60(12):1146-1156. doi: 10.3349/ymj.2019.60.12.1146.
Chemoresistance is a concern in ovarian cancer patients, in whom survival remains. MicroRNA, a novel class of small RNAs, have frequently been found to be dysregulated in human malignancies and to act as negative regulators of gene expression. This study aimed to explore the function of miR-338-3p in cisplatin resistance in ovarian cancer and potential molecular mechanisms thereof.
The expression levels of miR-338-3p and WNT2B in ovarian cancer tissues and cells were estimated by real-time quantitative polymerase chain reaction (RT-qPCR). In addition, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazol-3-ium bromide (MTT), transwell, and flow cytometry assays were used to assess biological role of miR-338-3p in vitro. Western blot assay was conducted to measure protein expression of WNT2B, epithelial-mesenchymal transition (EMT)-related proteins, and apoptosis-related proteins. The relationship between miR-338-3p and WNT2B was confirmed by dual-luciferase reporter. Finally, a xenograft tumor model was developed to explore the effects of overexpression of miR-338-3p on tumor growth in ovarian cancer in vivo.
MiR-338-3p was downregulated in cisplatin resistant ovarian cancer tissues and cells. Mechanistically, high expression of miR-338-3p enhanced cell sensitivity to cisplatin by inhibiting proliferation, motility, and EMT and by promoting apoptosis via targeting WNT2B expression in vitro. Furthermore, overexpression of miR-338-3p increased cisplatin sensitivity among ovarian cancer in an in vivo xenograft tumor model.
MiR-338-3p enhances the sensitivity of ovarian cancer cells to cisplatin by downregulating WNT2B.
化疗耐药性是卵巢癌患者关注的问题，因为此类患者的生存率仍然较低。微小 RNA 是一类新型小分子 RNA，其在人类恶性肿瘤中经常出现失调，并作为基因表达的负调节剂。本研究旨在探讨 miR-338-3p 在卵巢癌顺铂耐药中的作用及其潜在的分子机制。
采用实时定量聚合酶链反应（RT-qPCR）检测卵巢癌组织和细胞中 miR-338-3p 和 WNT2B 的表达水平。此外，采用 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基-2H-四唑溴盐（MTT）、Transwell 和流式细胞术检测 miR-338-3p 在体外的生物学作用。Western blot 检测 WNT2B、上皮-间充质转化（EMT）相关蛋白和凋亡相关蛋白的表达。通过双荧光素酶报告验证 miR-338-3p 与 WNT2B 之间的关系。最后，建立异种移植肿瘤模型，探讨 miR-338-3p 过表达对体内卵巢癌肿瘤生长的影响。
miR-338-3p 在顺铂耐药的卵巢癌组织和细胞中表达下调。机制上，miR-338-3p 的高表达通过抑制增殖、迁移和 EMT，促进凋亡，从而抑制 WNT2B 表达，增强卵巢癌细胞对顺铂的敏感性。此外，miR-338-3p 的过表达增加了体内异种移植肿瘤模型中卵巢癌对顺铂的敏感性。
miR-338-3p 通过下调 WNT2B 增强卵巢癌细胞对顺铂的敏感性。
