Silencing of MALAT1 inhibits migration and invasion by sponging miR-1-3p in prostate cancer cells
Silencing of MALAT1 inhibits migration and invasion by sponging miR-1-3p in prostate cancer cells
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DOI：
10.3892/mmr.2019.10602
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发表时间：
2019-10-01
影响因子：
3.4
通讯作者：
Wang, Hongliang
中科院分区：
文献类型：
--
作者：
Dai, Xiaofan;Liang, Zuowen;Wang, Hongliang
前列腺癌是一种常见的恶性肿瘤，死亡率很高。与肺腺癌转录物1（MALAT 1）相关的长非编码RNA转移已被报道起到肿瘤促进作用。然而，其根本机制需要进一步研究。在本研究中，证实了在前列腺癌细胞系中MALAT 1增加而microRNA（miR/miRNA）-1-3p减少。MALAT 1基因沉默可抑制细胞的迁移、侵袭和上皮-间质转化，而上皮（E）-钙粘蛋白表达水平升高，神经（N）-钙粘蛋白、波形蛋白、Slug和Snail表达水平降低。双荧光素酶报告基因检测结果表明，miR-1- 3 p与MALAT 1和coronin 1C（CORO 1C）3 '非翻译区结合，MALAT 1与CORO 1C竞争miR-1- 3 p的结合位点。MALAT 1抑制miR-1- 3 p的表达，反之亦然。MALAT 1敲低诱导CORO 1C下降，随后通过miR-1- 3 p抑制剂恢复。此外，通过抑制miR-1- 3 p或过表达CORO 1C，MALAT 1诱导的表型改变的沉默得以恢复。总之，MALAT 1作为可降解的miRNA海绵，可以从CORO 1C中隔离miR-1- 3 p，并且通过沉默MALAT 1，可以抑制前列腺癌细胞中的迁移、侵袭和上皮-间质转化。MALAT 1和CORO 1C可能成为前列腺癌的新的临床治疗靶点。
Prostate cancer is a common malignancy with a high mortality rate. Long non-coding RNA metastasis associated with lung adenocarcinoma transcript 1 (MALAT1) has been reported to serve tumor-promoting roles. However, the underlying mechanism requires further examination. In the present study, it was demonstrated that MALAT1 was increased while microRNA (miR/miRNA)-1-3p was decreased in prostate cancer cell lines. The silencing of MALAT1 inhibited migration, invasion and epithelial-mesenchymal transition, when epithelial (E)-cadherin expression level was increased, and neural (N)-cadherin, vimentin, Slug and Snail expression levels were decreased. Dual-luciferase reporter assay results demonstrated that miR-1-3p bound to MALAT1 and coronin 1C (CORO1C) 3 ' untranslated region, and MALAT1 competed with CORO1C for the binding sites of miR-1-3p. MALAT1 inhibited the expression of miR-1-3p and vice versa. MALAT1 knockdown induced the decline of CORO1C, which was subsequently recovered by the miR-1-3p inhibitor. In addition, by inhibiting miR-1-3p or overexpressing CORO1C, the silencing of MALAT1-induced phenotypic alterations were restored. In conclusion, MALAT1 serving as a degradable miRNA sponge, may sequester miR-1-3p from CORO1C and by silencing MALAT1, migration, invasion and epithelial-mesenchymal transition may be inhibited in prostate cancer cells. MALAT1 and CORO1C may serve as novel clinical therapeutic targets for prostate cancer.