The Down-Regulation of MicroRNA-497 Contributes to Cell Growth and Cisplatin Resistance Through PI3K/Akt Pathway in Osteosarcoma

Abstract

Background: Down-expression of microRNA-497 (miR-497) was often found in malignancies. The purposes of this study were to determine the expression of miR-497 in human osteosarcoma and to establish the association between miR-497 expression with cell survival and the sensitivity to cisplatin in human osteosarcoma cells. Methods: The effects of ectopic miR-497 expression on the cell survival and cisplatin sensitivity in osteosarcoma cells were measured by the Cell Counting Kit-8 (CCK-8) assay. Quantitative real-time PCR (qRT-PCR) was utilized to determine the expression of miR-497. The effects of ectopic miR-497 expression on the expression of VEGFA, Akt and p-Akt were determined by western blot. Results: Real-time quantitative PCR analysis revealed that miR-497 was significantly down-regulated in osteosarcoma tissues and in the osteosarcoma cell line SAOS-2 compared with adjacent nontumorous osteosarcoma tissues and normal human osteoblasts. Up-regulation of miR-497 inhibited cell survival and enhanced the sensitivity to cisplatin in osteosarcoma cells. In addition, knockdown of miR-497 induced osteosarcoma cells growth and cisplatin resistance. Luciferase reporter assay and western blot confirmed that VEGFA was a direct target of miR-497. PI3K inhibitor LY294002 abrogated miR-497 inhibitors induced cisplatin resistance. Conclusion: Taken together, our results suggest that miR-497 modulates the sensitivity to cisplatin at least in part through PI3K/Akt pathway in osteosarcoma cells.

Post-Transcriptional Control of Angiotensin II Type 1 Receptor Regulates Osteosarcoma Cell Death

“…Past studies have demonstrated the regulation effects of miRNAs on protein expression. MiRNAs combine with 3′-untranslated region (3′-UTR) of the mRNA of certain protein thus regulating the intracellular protein expression [20-24]. Many biological events including development of a tumor would be regulated by miRNAs [20-24].…”

“…MiRNAs combine with 3′-untranslated region (3′-UTR) of the mRNA of certain protein thus regulating the intracellular protein expression [20-24]. Many biological events including development of a tumor would be regulated by miRNAs [20-24]. In addition, the aberrant expression of miRNAs would contribute to OS initiation, progression, outgrowth, metastases, as well as resistance to chemotherapy [20-24].…”

“…Many biological events including development of a tumor would be regulated by miRNAs [20-24]. In addition, the aberrant expression of miRNAs would contribute to OS initiation, progression, outgrowth, metastases, as well as resistance to chemotherapy [20-24]. MiR-1248 is a rarely studied miRNA, and so far no reports have addressed to its biological function.…”

Expression Profiles of microRNAs in Drug-Resistant Non-Small Cell Lung Cancer Cell Lines Using microRNA Sequencing

“…Increasing evidence has shown that miRNAs play a vital role in drug resistance [7,8], which leads to treatment failure in cancer. For example, miR-497 sensitizes osteosarcoma cells to cisplatin (DDP), in part via the PI3K/Akt pathway [9]. MiR-17 and miR-92 families play a role in DDP resistance and can be considered novel biomarkers for platinum-based chemotherapy in NSCLC [10].…”

MicroRNA-661 Enhances TRAIL or STS Induced Osteosarcoma Cell Apoptosis by Modulating the Expression of Cytochrome c1

“…[7-9]. A recent microarray profiling study identified 177 miRNAs differentially expressed in osteosarcoma cell lines compared with normal bone, and the involvement of selected miRNAs was confirmed in clinical samples [10-12]. miR-661 was suggested to be involved in cancer, although its function is controversial.…”