Knockdown of lncRNA ACTA2-AS1 reverses cisplatin resistance of ovarian cancer cells via inhibition of miR-378a-3p-regulated Wnt5a
| Autor: | Chenxiao Lin, Meiyun Zheng, Youlin Yang, Yi Chen, Xiahui Zhang, Lingping Zhu, Haiyan Zhang |
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| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | Bioengineered. 13:9829-9838 |
| ISSN: | 2165-5987 2165-5979 |
| Popis: | Cisplatin (DDP) resistance is a principal cause leading to poor prognosis in females suffering from ovarian cancer (OC). Long non-coding RNA (lncRNA) has been shown to have an involvement in regulating cellular processes; chemoresistance being one of them the precise object of this work was to probe into the role of lncRNA ACTA2-AS1 in OC cells that have developed DDP resistance. We developed DDP-resistant OC cell lines (A2780/DDP and SKOV3/DDP). The influence of the ACTA2-AS1/miR-378a-3p/Wnt5a axis on DDP chemoresistance of DDP-resistant OC cells was ascertained using real-time PCR, Elisa, and CCK-8, and dual-luciferase reporter assay. In DDP-resistant cells and tissues, ACTA2-AS1 was increased, while a substantial downregulation in miR-378a-3p was noticed. In cells manifesting DDP-resistance, knocking down ACTA2-AS1 boosted the expression of miR-378a-3p. Further research into the mechanism of ACTA2-AS1 revealed that it acted as a 'sponge' by getting involved in a competition against miR-378a-3p binding to modify its target Wnt5a. The suppression of DDP-resistance in OC cells caused by ACTA2-AS1 downregulation was reversed by silencing miR-378a-3p. Furthermore, via inhibition of Wnt5a, miR-378a-3p alleviated DDP resistance in OC cells. These findings show that for miR-378a-3p, ACTA2-AS1 works like a sponge thus preventing it from binding to Wnt5a and boosting OC cell DDP resistance. Our research will aid the expansion of plausible therapeutic options for treating OC. |
| Databáze: | OpenAIRE |
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