Haiyan Zhang

Knockdown of lncRNA ACTA2-AS1 reverses cisplatin resistance of ovarian cancer cells via inhibition of miR-378a-3p-regulated Wnt5a

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.

circ_ZFR Is Linked to Paclitaxel Resistance in Cervical Cancer via miR-944 Sponging and IL-10 Upregulation

Objective. Cervical cancer (CC) has an elevated rate of invasion and death despite surgical treatment, radiotherapy, and chemotherapy. Several studies revealed that circRNAs have a key contribution to the resistance of drugs against different types of carcinomas. The goal of the existing study was to figure out what role circ_ZFR plays in paclitaxel (PTX) resistance in cervical cancer (CC) patients. Materials and Methods. Herein, two types of CC cells (SiHa/PTX and Hela/PTX) were utilized. The levels of IL-10 mRNA, miR-944, and circ_ZFR were measured using qRT-PCR analyses. The CCK-8 assay was used to determine PTX resistance. The IL-10 expression was measured via the ELISA technique. The combination of miR-944 and circ_ZFR or IL-10 was validated using a dual-luciferase reporter (DLR) assay. Results. The amount of circ_ZFR was increased in PTX-resistant CC cells and tissues. In PTX-resistant CC cells, knocking down circ_ZFR expression decreased PTX resistance. circ_ZFR knockdown significantly reduced IL-10 expression via sponging miR-944, increasing PTX sensitivity in PTX-resistant CC cells. Conclusion. circ_ZFR knockdown has a considerable role in overwhelming CC-associated PTX resistance by modifying the axis of miR-944/IL-10 axis, suggesting that developing a circRNA target-based treatment could be considered prevent CC progression.