Epigenetic silencing of microRNA-199a-5p promotes the proliferation of non-small cell lung cancer cells by increasing AKAP1 expression.
Epigenetic silencing of microRNA-199a-5p promotes the proliferation of non-small cell lung cancer cells by increasing AKAP1 expression.
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DOI：
10.3892/ol.2021.12695
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发表时间：
2021-06
期刊：
影响因子：
2.9
通讯作者：
Jiang L
中科院分区：
文献类型：
--
作者：
Yang N;Liang Y;Zhu T;Long Y;Chen Z;Zhang X;Jiang L
MicroRNA (miR)-199a-5p 表达在多种恶性肿瘤中下调，包括非小细胞肺癌 (NSCLC)，其低表达与不良预后相关。然而，据我们所知，NSCLC 中 miR-199a-5p 下调的机制及其靶效应物仍有待阐明。本研究揭示了与癌旁组织和肺上皮细胞系相比，NSCLC 组织和细胞系中 miR-199a-5p 表达下调。进一步的实验表明，与癌旁组织相比，NSCLC组织中miR-199a启动子的甲基化水平明显更高。 DNA甲基转移酶抑制剂5-Aza-2'-脱氧胞苷显着增加NSCLC细胞中miR-199a-5p的表达水平。此外，还发现 miR-199a-5p 模拟物转染通过靶向 AKAP1 mRNA 的 3' 非翻译区，在 mRNA 和蛋白质水平上降低了 A-激酶锚定蛋白 1 (AKAP1) 的表达水平。体外实验表明，miR-199a-5p过表达抑制NSCLC细胞的增殖和致瘤性，而AKAP1过表达部分恢复恶性表型，表明AKAP1可能是miR-199a-5p靶向的下游效应子。总的来说，目前的研究结果表明 miR-199a-5p 可能是 AKAP1 的新型调节因子，并且 miR-199a-5p 可能是 NSCLC 中潜在的肿瘤抑制因子。
MicroRNA (miR)-199a-5p expression is downregulated in a variety of malignancies, including non-small cell lung cancer (NSCLC), and its low expression is associated with a poor prognosis. However, to the best of our knowledge, the mechanism underlying miR-199a-5p downregulation in NSCLC and its target effectors remain to be elucidated. The present study revealed the downregulation of miR-199a-5p expression in NSCLC tissues and cell lines compared with in para-carcinoma tissues and a lung epithelial cell line. Further experiments indicated that the methylation levels of the miR-199a promoter were markedly higher in NSCLC tissues compared with in para-carcinoma tissues. The DNA methyltransferase inhibitor 5-Aza-2′-deoxycytidine markedly increased the expression levels of miR-199a-5p in NSCLC cells. Furthermore, it was identified that miR-199a-5p mimics transfection decreased the expression levels of A-kinase anchoring protein 1 (AKAP1) at both the mRNA and protein levels by targeting the 3′ untranslated region of AKAP1 mRNA. The in vitro experiments demonstrated that miR-199a-5p overexpression inhibited the proliferation and tumorigenicity of NSCLC cells, whereas overexpression of AKAP1 partially recovered the malignant phenotypes, suggesting that AKAP1 may be a downstream effector targeted by miR-199a-5p. Collectively, the present findings indicated that miR-199a-5p may be a novel regulator of AKAP1, and that miR-199a-5p may be a potential tumor suppressor in NSCLC.
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