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Abstract
BackgroundAs 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.MethodsBased 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.ResultsWe found that the miR-20a-5p level was higher in G-292 cells than in SJSA-1 cells. Forced expression of miR-20a-5p counteracted OS chemoresistance in both cell culture and tumor xenografts in nude mice. As one of miR-20a-5p’s targets, SDC2 was found to mediate the miR-20a-5p-induced repression of OS chemoresistance.ConclusionsOur results suggest that miR-20a-5p and SDC2 contribute to OS chemoresistance. The key players in the miR-20a-5p/SDC2 axis may be a potential diagnostic biomarker and therapeutic target for OS patients.
Highlights
As one of the hallmarks of cancer, chemoresistance hinders curative cancer chemotherapy in osteosarcoma (OS)
syndecan 2 (SDC2) is a positive regulator of the multi‐chemoresistance of OS Our previous result suggested that G-292 and SJSA-1 cell lines are the multi-chemosensitive and multi-chemoresistant OS cell lines, respectively [22]
The results showed that a dozen of miRNAs were differentially expressed in the SJSA-1 and the G-292 cells and miR-20a-5p was selected as one of the studied target miRNAs
Summary
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. MiRNAs are a class of small non-coding regulatory RNA molecules that have been shown to be involved in a wide range of biological processes [1]. Their dysregulation has been associated with the development of diseases including cancer. MiR-20, Rest and Wnt signaling is suggested to be involved in a regulatory circuit that can modulate the neural differentiation of neural progenitor cells [16]. It was found that miR-20a induces cell radio-resistance by activating the PTEN/PI3K/Akt signaling pathway in hepatocellular carcinoma [17]
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