The miR-34a-5p promotes the multi-chemoresistance of osteosarcoma via repression of the AGTR1 gene

Abstract

BackgroundChemoresistance hinders the curative cancer chemotherapy. MicroRNAs (miRNAs) are key players in diverse biological processes including the chemoresistance of cancers.MethodsA RNA-seq-based miR-omic analysis of osteosarcoma (OS) cells was performed to detect the levels of miR-34a-5p. Bioinformatics analysis revealed that AGTR1 is one of the target genes of miR-34a-5p. The mRNA and protein levels of AGTR1 were detected in both the miR-34a-5p-mimic transfected G-292 and miR-34a-5p-antagomiR transfected SJSA-1 cells. The involvement of AGTR1 with OS chemoresistance was validated by the experiments with siRNA-mediated repression or overexpression of the AGTR1 gene.ResultsWe showed that miR-34a-5p promotes the multi- chemoresistance of OS. The angiotensin II type 1 receptor (AGTR1) gene, is one of the targets of miR-34a-5p in OS and thus negatively correlates with OS chemoresistance by systematic investigations of a multi-drug sensitive (G-292) and resistant (SJSA-1) OS cell lines. Down-regulation of the AGTR1 expression by siRNA passivates G-292 cells and suppresses cell apoptosis, while over-expression of AGTR1 sensitizes SJSA-1 cells and thus promotes the drug-triggered cell death.ConclusionsThe miR-34a-5p and its target gene AGTR1 are the potential targets for an effective chemotherapy of OS. Our results also provide novel insights into the effective chemotherapy for OS patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-3002-x) contains supplementary material, which is available to authorized users.

Circulating microRNA-34 family low expression correlates with poor prognosis in patients with non-small cell lung cancer

“…Partially in line with this result, we found that miR-34a high expression was correlated with prolonged DFS and OS compared to low expression in this study, which partly resulted from its regulation of several pathways or genes, including c-MET and G1 phase regulators, to cause the inhibition of tumorigenesis and lymphatic invasion, thereby affecting recurrence of NSCLC patients (35). In addition, miR-34a increases the sensitivity of chemotherapy and radiotherapy, decreasing recurrence of NSCLC patients (36,37). Subsequently, Cox regression analysis was performed to evaluate factors affecting DFS and OS in this study, we also observed that plasma miR-34a was correlated with prolonged DFS and OS in univariate Cox model, while it could not independently predict DFS and OS of NSCLC patients in multivariate Cox model.…”

Cancer-associated fibroblasts contribute to oral cancer cells proliferation and metastasis via exosome-mediated paracrine miR-34a-5p

“…Zhang et al showed that CAFs enhance the malignant phenotype transition of hepatocellular carcinoma through transferring miR-320a-devoid exosomes to cancer cells, and that the miR-320-PBX3 axis increases the motility of hepatocellular carcinoma cells via activating the MAPK pathway [ 43 ]. Although studies have shown the effect of dysregulated miR-34a-5p in colorectal cancer [ 25 ] and osteosarcoma [ 26 , 44 ], the underlying mechanisms of miR-34a-5p in OSCC progression have not been elucidated. Our study provides evidence that miR-34a-5p overexpression could inhibit the proliferation and motility of OSCC cells in vitro and in vivo.…”

The study of mechanism of miR-34c-5p targeting FLOT2 to regulate proliferation, migration and invasion of osteosarcoma cells

“…miRNA regulates the important pathophysiological processes in the development, progression, metastasis and chemotherapy of osteosarcoma, providing new ideas for targeted therapy of osteosarcoma [12]. miR-34a-5p [13] and miR-20a-5p [14] can increase the chemosensitivity of osteosarcoma cells; miR-34a inhibits tumor invasion and metastasis of osteosarcoma by affecting C-IAP2 and Bcl-2 [15]. In addition, miR-34a can also reduce the self-renewal ability, tumorigenic activity and invasive ability of cancer stem cells [16].…”