RESUMEN
Background: While there is prior evidence for the ability of circular RNAs (circRNAs) to shape the cisplatin (DDP) resistance of cancers in human patients, there has been relatively little research to date focused on the interplay between circRNAs and DDP resistance in the context of OSCC progression to date. In the present analysis, the functional role that circ_0000140 plays as a mediator of chemoresistance to DDP was thus explored in greater detail. Methods: Both qPCR and Western immunoblotting were employed as appropriate to detect circ_0000140, miR-527, and SLC7A11 levels, while interactions among these factors were detected through RNA immunoprecipitation, RNA pull-down, and dual luciferase report assays. MTT assays were used to assess cellular viability as a means of gauging DDP sensitivity. Results: Both tissue samples from DDP-resistant OSCC patient tumors and OSCC cell lines resistant to DDP exhibited pronounced circ_0000140 upregulation. Knocking down this circRNA significantly increased the DDP sensitivity of both tested DDP-resistant OSCC cell lines and promoted ferroptosis, whereas knocking down miR-527 was sufficient to reverse these effects, which were recapitulated by miR-527 overexpression. Conversely, the effects of overexpressing miR-527 were reversed by the restoration of SLC7A11 expression. Consistently, this circRNA was able to increase DDP IC50 values and to suppress ferroptosis in both tested cell lines through this miR-527/SLC7A11 signaling axis. Conclusion: These results revealed that circ_0000140/miR-527/SLC7A11-mediated ferroptosis may provide novel insights into the development of this cancer type and the emergence of chemoresistance in the future.
RESUMEN
Objective: To investigate the effects of microRNA-23a (miR-23a-3p) and Runx2 on malignant progression of oral cancer cells and their possible molecular mechanisms. Methods: Fluorescence quantitative PCR (qPCR) was used to detect the expression of miR-23a-3p and Runx2 in human oral squamous cell carcinoma tissues and paracancerous tissues. The dual luciferase reporter assay was used to evaluate the targeted regulation of miR-23a-3p on Runx2. A subcutaneous xenograft model was established to investigate the tumor-suppressive effect of miR-23a-3p. Cells were transfected with miR-23a-3p mimics and negative control NC. CCK-8 assay, EDU assay, Transwell assay, and clone formation assay were used to detect malignant evolution of cells. Western blotting was used to detect the expression of Runx2, PTEN, and PI3K/Akt. The cells were simultaneously transfected with miR-23a-3p mimics and Runx2 to detect the malignant evolution of cells. Results: The expression of miR-23a-3p was downregulated in oral squamous cell carcinoma tissues, while the expression of Runx2 was upregulated. Overexpression of miR-23a-3p or inhibition of Runx2 inhibited the malignant progression of oral squamous cell carcinoma CAL-27 and TSCCA. Overexpression of miR-23a-3p inhibits the growth of oral cancer tumors. miR-23a-3p inhibits the PTEN/PI3K/Akt signaling pathway through Runx2. Overexpression of Runx2 reverses the tumor-suppressive effect of miR-23a-3p. Conclusion: miR-23a-3p can inhibit the PI3K/Akt signaling pathway by targeting Runx2 and inhibit the malignant evolution of oral cancer.
