MALAT1 promotes osteosarcoma development by targeting TGFA via MIR376A.
MALAT1 promotes osteosarcoma development by targeting TGFA via MIR376A.
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MALAT1 通过 MIR376A 靶向 TGFA 促进骨肉瘤发展
DOI：
10.18632/oncotarget.10752
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发表时间：
2016-08-23
期刊：
影响因子：
--
通讯作者：
Li Y
中科院分区：
文献类型：
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作者：
Luo W;He H;Xiao W;Liu Q;Deng Z;Lu Y;Wang Q;Zheng Q;Li Y
转移相关肺腺癌转录物1（MALAT 1）是一种长链非编码RNA（lncRNA），其有助于许多实体瘤（包括骨肉瘤（OS））的起始和发展。在这里，我们发现MALAT 1在人OS细胞系和组织中增加并促进OS细胞生长，而MALAT 1敲低抑制OS细胞生长。我们还检测到OS组织中OS生长抑制因子MIR 376 A的下调和OS生长促进因子TGFA的上调。TGFA表达与MALAT 1表达呈正相关，两者均与MIR 376 A表达呈负相关。MIR 376 A与MALAT 1之间通过位于MALAT 1 3′-非翻译区（3′-UTR）的MIR 376 A结合位点直接相互作用。MIR 376 A与TGFA 3′-UTR之间也存在直接的相互作用。因此，MALAT 1可以通过抑制MIR 376 A促进OS细胞生长，导致TGFA表达增加。我们的结果表明MALAT 1/MIR 376 A/TGFA轴介导OS细胞增殖和肿瘤进展。
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.