Abstract

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long non-coding RNA (lncRNA) that contributes to the initiation and development of many solid tumors, including osteosarcoma (OS). Here, we showed that MALAT1 was increased in human OS cell lines and tissues and promoted OS cell growth, while MALAT1 knockdown suppressed OS cell growth. We also detected downregulation of MIR376A, a suppressor of OS growth, and upregulation of TGFA, a promoter of OS growth, in OS tissues. TGFA expression was positively correlated with MALAT1 expression, and both were negatively correlated with MIR376A expression. There was a direct interaction between MIR376A and MALAT1 via a putative MIR376A binding site within the MALAT1 3′-untranslated region (3′-UTR). There was also a direct interaction between MIR376A and the TGFA 3′-UTR. Thus, MALAT1 may promote OS cell growth through inhibition of MIR376A, leading to increased expression of TGFA. Our results suggest a MALAT1/MIR376A/TGFA axis mediates OS cell proliferation and tumor progression.

Highlights

  • More than 90% of the human DNA sequence is actively transcribed but only 2% of it encodes protein

  • Several long noncoding RNA (lncRNA) play an oncogenic role in breast, gastric, colorectal, and cervical cancers [7], while others function as tumor suppressors in hepatocellular carcinoma and gastric cancer [8, 9]

  • The lncRNA Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is upregulated in many cancers, including OS [12, 13, 20]

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Summary

Introduction

More than 90% of the human DNA sequence is actively transcribed but only 2% of it encodes protein. The majority of transcripts are referred to as non-coding RNAs (ncRNAs) [1, 2]. Small non-coding RNAs, especially, microRNAs, have been studied extensively and their roles in gene regulation and cellular function have been elucidated in numerous cancers [2]. Long non-coding RNAs (lncRNAs) have been reported to play important roles during development and in diseases, including cancer [3, 4]. LncRNAs can be oncogenic or function as tumor suppressors [5, 6]. Several lncRNAs play an oncogenic role in breast, gastric, colorectal, and cervical cancers [7], while others function as tumor suppressors in hepatocellular carcinoma and gastric cancer [8, 9]. In osteosarcoma (OS), expression of several lncRNAs may be upregulated [10, 11]

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