MALAT1 induces osteosarcoma progression by targeting miR‐206/CDK9 axis

Abstract

Long noncoding RNAs (LncRNAs) have been reported to participate in cancer development, including osteosarcoma. Here, in our study, we observed that lncRNA metastasis-associated lung adenocarcinoma transcription 1 (MALAT1) was remarkably overexpressed in osteosarcoma. However, the role it plays in osteosarcoma proliferation mediated by miR-206/cyclin-dependent kinase 9 (CDK9) axis remains uninvestigated. It was found that miR-206 was decreased and CDK9 was elevated in human osteosarcoma cells including MG63, Saos-2, U2OS, and KHOS compared with human osteoblast cell line hFOB 1.19. In addition, it was exhibited that knockdown of MALAT1 was able to inhibit osteosarcoma cell proliferation, which suggested that MALAT1 played an oncogenic role in osteosarcoma development. Bioinformatics analysis indicated that MALAT1 can function as a competing endogenous RNA by sponging miR-206. Because miR-206 has been identified as a significant tumor suppressive gene in multiple cancers, we validated that mimics of miR-206 can restrain osteosarcoma progression. Furthermore, dual-luciferase reporter assay, RNA binding protein immunoprecipitation, and RNA pull-down assay demonstrated the correlation between miR-206 and MALAT1. Besides these, CDK9 was predicted as a downstream gene of miR-206, and we observed that MALAT1 can regulate osteosarcoma progress by modulating CDK9 expression via sponging miR-206. In conclusion, our study implied that MALAT1/miR-206/CDK9 axis can provide novel insights into the biological mechanism of osteosarcoma progression.

LncRNA MALAT1 facilitates lung metastasis of osteosarcomas through miR-202 sponging

“…It needs to be mentioned that while we found MALAT1 to be upregulated in metastatic osteosarcomas and that an oncogenic role of MALAT1 in osteosarcoma is supported by many reports 23 , 27 , 31 – 36 , there are indications of a tumor suppressive role of MALAT1 37 . In this specific report, downregulation of MALAT1 was found to increase lung metastases of breast cancer cells 37 .…”

“…The focus of our work on lncRNAs is supported by several reports that have documented role of lncRNAs in cancer progression and metastasis 17 – 21 . In osteosarcoma as well, there are many reports on lncRNAs 19 , 22 – 27 . Based on these evidences, it is clear that lncRNAs can influence proliferation and metastasis of osteosarcoma cells.…”

“…However, we further studied the mechanism by evaluating the possible role of miRNA sponging by MALAT1. lncRNAs mode of functioning through sponging of miRNAs is well known 23 , 24 , 27 , 28 . In our screening, which involved miRNAs documented to be targets of MALAT1 as well as some revealed by online prediction tools, the two miRNAs that clearly stood out were miR-202 and miR-34a.…”

TNK2‐AS1 upregulated by YY1 boosts the course of osteosarcoma through targeting miR‐4319/WDR1

“…DANCR has been reported to accelerate OS progression by enhancing AXL receptor tyrosine kinase by ‘sponging’ miR‐33a‐5p and 11 SNHG15 boosted cell invasion, autophagy, and proliferation in OS by absorbing miR‐141 12 . lncRNA MALAT1 acted as a ceRNA against CDK9 to promote OS progression by absorbing miR‐206 13 . In this study, we analyzed the possible ceRNA role of TNK2‐AS1 in OS, as well as downstream molecules.…”

Identification of prognostic biomarkers for breast cancer based on miRNA and mRNA co‐expression network

“…Moreover, it has been proven by various research that overexpression of miR‐133b, miR‐206, miR‐525, and miR‐527 can promote various types of cancers including ovarian cancer and osteosarcoma. It also promotes cell proliferation, migration, and invasion; and induces apoptosis which is consistent with our findings.…”