Overexpression of microRNA-195-5p reduces cisplatin resistance and angiogenesis in ovarian cancer by inhibiting the PSAT1-dependent GSK3β/β-catenin signaling pathway (Retracted article. See vol. 20, 2022)
Overexpression of microRNA-195-5p reduces cisplatin resistance and angiogenesis in ovarian cancer by inhibiting the PSAT1-dependent GSK3β/β-catenin signaling pathway (Retracted article. See vol. 20, 2022)
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DOI：
10.1186/s12967-019-1932-1
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发表时间：
2019-06-06
影响因子：
7.4
通讯作者：
Kong, Beihua
中科院分区：
文献类型：
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作者：
Dai, Jun;Wei, Rujia;Kong, Beihua
背景卵巢癌（ovarian cancer，OC）是女性癌症相关死亡的主要原因之一。MicroRNAs（miRs）在OC的发生、发展中起着重要作用。因此，本研究旨在探讨miR-195- 5 p对卵巢癌顺铂（DDP）耐药和血管生成的影响及其机制。采用RNA定量分析法检测miR-195- 5 p在OC组织和细胞中的表达模式。通过检测上调或下调miR-195- 5 p或PSAT 1或阻断糖原合成酶激酶-3（GSK 3）/β-catenin信号通路后OC细胞的DDP抗性、凋亡和血管生成，评价miR-195- 5 p在OC中的作用。结果miR-195 - 5 p可直接靶向PSAT 1，下调其表达。OC组织中miR-195- 5 p的表达低于癌旁正常组织，而PSAT 1的表达高于癌旁正常组织。当miR-195- 5 p过表达或PSAT 1沉默时，HIF-1、VEGF、PSAT 1、β-catenin的表达以及GSK 3磷酸化程度均降低，血管生成减少，DDP耐药降低，细胞凋亡增加。结论miR-195- 5 p过表达可降低OC的血管生成，降低顺铂耐药，为OC的治疗提供了一个潜在的靶点。
BackgroundOvarian cancer (OC) is one of the leading causes for cancer-related deaths among women. MicroRNAs (miRs) have been proved to be vital to the development and progression of OC. Hence, the study aims to evaluate the ability of miR-195-5p affecting cisplatin (DDP) resistance and angiogenesis in OC and the underlying mechanism.MethodsMiRs that could target phosphoserine aminotransferase 1 (PSAT1), a differentially expressed gene in OC, were predicted by miRNA-mRNA prediction websites. The expression patterns of miR-195-5p in the OC tissues and cells were determined using RNA quantification assay. The role of miR-195-5p in OC was evaluated by determining DDP resistance, apoptosis and angiogenesis of OC cells after up-regulating or down-regulating miR-195-5p or PSAT1, or blocking the glycogen synthase kinase-3 (GSK3)/-catenin signaling pathway. Animal experiment was conducted to explore the effect of miR-195-5p on resistance to DDP and angiogenesis.ResultMiR-195-5p directly targeted PSAT1 and down-regulated its expression. The expression of miR-195-5p was lower while that of PSAT1 was higher in OC tissues than in adjacent normal tissues. When miR-195-5p was over-expressed or PSAT1 was silenced, the expression of HIF-1, VEGF, PSAT1, -catenin as well as the extent of GSK3 phosphorylation was reduced, the angiogenesis and resistance to DDP was diminished and apoptosis was promoted both in vitro and in vivo. The inhibition of GSK3/-catenin signaling pathway was involved in the regulation process.ConclusionOver-expression of miR-195-5p reduced angiogenesis and DDP resistance in OC, which provides a potential therapeutic target for the treatment of OC.