MiR-20a-5p represses the multi-drug resistance of osteosarcoma by targeting the SDC2 gene

Background: As one of the hallmarks of cancer, chemoresistance hinders curative cancer chemotherapy in osteosarcoma (OS). MicroRNAs (miRNAs) act as key regulators of gene expression in diverse biological processes including the multi-chemoresistance of cancers. Methods: Based on the CCK8 experiments, we performed an RNA-seq-based miR-omic analysis of osteosarcoma (OS) cells (a multi-chemosensitive OS cell line G-292 and a multi-chemoresistant OS cell line SJSA-1) to detect the levels of miR-20a-5p. We predicted Homo sapiens syndecan 2 (SDC2) as one of the target genes of miR-20a-5p via several websites, which was further validated by detecting their expression of both mRNA and protein level in both the miR-20a-5p-mimic transfected G-292 and miR-20a-5p-antagomiR transfected SJSA-1 cells. The involvement of SDC2 with OS chemoresistance was checked by siRNA-mediated repression or overexpression of SDC2 gene. Cell viability was assessed by CCK8 assay. Results: We found that the miR-20a-5p level was higher in G-292 cells than in SJSA-1 cells. Forced expression of miR20a-5p counteracted OS chemoresistance in both cell culture and tumor xenografts in nude mice. As one of miR-20a5p's targets, SDC2 was found to mediate the miR-20a-5p-induced repression of OS chemoresistance. Conclusions: Our results suggest that miR-20a-5p and SDC2 contribute to OS chemoresistance. The key players in the miR-20a-5pSDC2 axis may be a potential diagnostic biomarker and therapeutic target for OS patients.