Scientific Research Department, Changsha Health Vocational College, Changsha, P.R. China.
Department of Obstetrics and Gynecology, The Fist Hospital of Hunan University of Chinese Medicine, Changsha, P.R. China.
J Gynecol Oncol. 2022 Nov;33(6):e81. doi: 10.3802/jgo.2022.33.e81.
Resistance to chemotherapy drugs makes ovarian cancer (OC) difficult to treat and ultimately kills patients. Long non-coding RNAs are closely related to carboplatin resistance in OC. In present study, we explored the role of lncRNA X-inactive specific transcript (XIST) on carboplatin resistance in OC.
Cell viability, proliferation, and apoptosis were assessed through 2,5-diphenyl-2H-tetrazolium bromide, colony formation, and flow cytometry assays, respectively. Microtubule-associated protein 1A/1B-light chain 3 expression was evaluated by immunofluorescence assay to analyze the cell autophagy. The interaction of XIST/miR-506-3p or miR-506-3p/forkhead box protein P1 (FOXP1) was analyzed using RNA immunoprecipitation (RIP) and dual-luciferases reporter assays. The function of XIST/miR-506-3p/FOXP1 axis in vivo was further confirmed by tumor xenograft study and immunohistochemistry.
The expression of XIST and FOXP1 increased while miR-506-3p decreased in OC and carboplatin resistance cells. XIST silencing repressed the proliferative and autophagic capacities of carboplatin resistance cells while promoted the apoptosis. XIST overexpression led to the opposite results. XIST targeted miR-506-3p and downregulated its expression. MiR-506-3p inhibition facilitated the proliferative and autophagic capacities while suppressed the apoptosis of cells, XIST knockdown reversed these effects. MiR-506-3p bound to FOXP1. XIST knockdown or miR-506-3p overexpression reversed the increase of cell proliferative and autophagic abilities and the decrease of apoptosis rate induced by FOXP1 overexpression. XIST affected autophagy and carboplatin resistance in vivo via regulating the miR-506-3p/FOXP1 axis.
XIST knockdown inhibited autophagy and carboplatin resistance of OC through FOXP1/protein kinase B (AKT)/mammalian target of rapamycin pathway by targeting miR-506-3p.
化疗药物耐药使卵巢癌（OC）难以治疗，最终导致患者死亡。长链非编码 RNA 与 OC 对卡铂的耐药性密切相关。本研究探讨了 X 染色体失活特异性转录物（XIST）在 OC 卡铂耐药中的作用。
通过 2,5-二苯基-2H-四唑溴盐、集落形成和流式细胞术分别评估细胞活力、增殖和凋亡。通过免疫荧光分析微管相关蛋白 1A/1B-轻链 3 的表达来分析细胞自噬。使用 RNA 免疫沉淀（RIP）和双荧光素酶报告基因检测分析 XIST/miR-506-3p 或 miR-506-3p/叉头框蛋白 P1（FOXP1）的相互作用。通过肿瘤异种移植研究和免疫组织化学进一步证实 XIST/miR-506-3p/FOXP1 轴在体内的功能。
OC 和卡铂耐药细胞中 XIST 和 FOXP1 的表达增加，而 miR-506-3p 的表达降低。XIST 沉默抑制了卡铂耐药细胞的增殖和自噬能力，同时促进了细胞凋亡。XIST 的过表达则产生相反的结果。XIST 靶向 miR-506-3p 并下调其表达。miR-506-3p 抑制促进了细胞的增殖和自噬能力，同时抑制了细胞凋亡，XIST 敲低逆转了这些效应。miR-506-3p 结合 FOXP1。XIST 敲低或 miR-506-3p 过表达逆转了 FOXP1 过表达诱导的细胞增殖和自噬能力增加以及凋亡率降低。XIST 通过调节 miR-506-3p/FOXP1 轴在体内影响自噬和卡铂耐药。
XIST 敲低通过靶向 miR-506-3p 抑制 FOXP1/蛋白激酶 B（AKT）/哺乳动物雷帕霉素靶蛋白通路，抑制 OC 自噬和卡铂耐药。
