MALAT1 promotes osteosarcoma development by regulation of HMGB1 via miR-142–3p and miR-129–5p

Abstract

Recently, emerging evidence has demonstrated that metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a long non-coding RNAs (lncRNAs), contributes to the initiation and development of tumors, including osteosarcoma (OS). Multiple studies have suggested an oncogenic role of MALAT1 and high-mobility group protein B1 (HMGB1) in OS tumorigenesis and metastasis, but the effects and mechanisms are not unanimous. Here, we showed that MALAT1 and HMGB1 were significantly increased in human OS cell lines and knockdown of MALAT1 reduced HMGB1 expression. By using online tools, we screen out 2 candidate miRNAs, miR-142-3p and miR-129-5p which may be associated with both MALAT1 and HMGB1. Luciferase reporter assay revealed a direct interaction between the 2 miRNAs and MALAT1, respectively, via a putative binding site within MALAT1. Meanwhile, both the 2 miRNAs could bind to HMGB1 3'-untranslated region (3'-UTR) and regulate HMGB1 expression. Moreover, knockdown of MALAT1 decreased HMGB1 expression, inhibited OS cell growth and promoted apoptosis, while miR-142-3p and miR-129-5p inhibitor partly restored the inhibitory effect of MALAT1 knockdown on HMGB1 expression, OS cell growth and the promotion of apoptosis. In OS tissues, the expression of MALAT1 and HMGB1 was upregulated while the expression of miR-142-3p and miR-129-5p was downregulated. Together, our results support a MALAT1/miR-142-3p/miR-129-5p/HMGB1 axis in OS cell proliferation and tumor progression. MALAT1 promoted OS cell growth through inhibition of miR-142-3p or miR-129-5p and by targeting HMGB1.

Administration of resveratrol improved Parkinson’s disease‐like phenotype by suppressing apoptosis of neurons via modulating the MALAT1/miR‐129/SNCA signaling pathway

“…31 Consistent with these results, a previous study also demonstrated that the expression of MALAT1 was increased in the midbrain tissues of mice suffering from MPTP-induced PD. 33 Furthermore, computational analyses have predicted that two miRNAs, miR-129-5p, and miR-142-3p, might be involved in the regulation of MALAT1 and HMGB1, 18 because MALAT1 enhanced the growth of OS cells and increased the expression of HMGB1 by suppressing the expression of miR-129-5p and miR-142-3p. 33 Furthermore, computational analyses have predicted that two miRNAs, miR-129-5p, and miR-142-3p, might be involved in the regulation of MALAT1 and HMGB1, 18 because MALAT1 enhanced the growth of OS cells and increased the expression of HMGB1 by suppressing the expression of miR-129-5p and miR-142-3p.…”

“…32 In addition, PD patients were also associated with substantially increased expression of miR-9-5p, miR-9-3p, miR-7, miR-129, and miR-132. 18 In this study, we used a luciferase reporter system to show that MALAT1 acted as an inhibitor of miR-129 and activated the MALAT1/miR-129/SCNA signaling pathway upon resveratrol treatment. 18 In this study, we used a luciferase reporter system to show that MALAT1 acted as an inhibitor of miR-129 and activated the MALAT1/miR-129/SCNA signaling pathway upon resveratrol treatment.…”

lncRNA TUG1-Mediated Mir-142-3p Downregulation Contributes to Metastasis and the Epithelial-to-Mesenchymal Transition of Hepatocellular Carcinoma by Targeting ZEB1

“…For example, miR-142-3p overexpression increases the chemosensitivity of non-small cell lung cancer (NSCLC) by inhibiting high-mobility group box 1-mediated autophagy Chen et al [14]. In addition, it can modulate osteosarcoma progression by interacting with metastasisassociated lung adenocarcinoma transcript-1 Liu et al [15]. Some studies have examined the biological role of miR-142-3p in HCC.…”

LncRNA TNRC6C‐AS1 regulates UNC5B in thyroid cancer to influence cell proliferation, migration, and invasion as a competing endogenous RNA of miR‐129‐5p

“…8 MiR-129-5p's antitumor effect has been identified in various malignancies, such as hepatocellular carcinoma, 14,15 breast cancer, 16 and osteosarcoma. 17 In TC, miR-129-5p was also downregulated and exerted positive effects on restraining tumor growth by silencing RET. 18 MiR-129-5p overexpression induced by histone deacetylase inhibitors could promote cell apoptosis of TC cells, 19 indicating its tumor suppressive role in TC.…”