MALAT1 promotes osteosarcoma development by targeting TGFA via MIR376A

Metastasis-associated lung adenocarcinoma transcript 1 ( MALAT1) is a long noncoding 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.