miR-429 promotes the proliferation of non-small cell lung cancer cells via targeting DLC-1 (Retracted article. See vol. 22, 2021)
miR-429 promotes the proliferation of non-small cell lung cancer cells via targeting DLC-1 (Retracted article. See vol. 22, 2021)
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DOI：
10.3892/ol.2016.4904
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发表时间：
2016-09-01
期刊：
影响因子：
2.9
通讯作者：
Zhou, Hui
中科院分区：
文献类型：
--
作者：
Xiao, Peng;Liu, Wenliang;Zhou, Hui
microRNA（miR）-200家族已被证明与多种类型的人类癌症（包括非小细胞肺癌（NSCLC））的肿瘤发生和进展相关。作为miR-200家族的成员，miR-429最近被鉴定为在NSCLC中具有致癌作用。然而，miR-429在NSCLC生长中的作用以及潜在的机制仍有待充分阐明。在本研究中，NSCLC细胞系H1229分别用miR-429模拟物或抑制剂转染。观察到miR-429的过表达导致NSCLC细胞增殖显著增加，而miR-429的敲低抑制H1229细胞的增殖。生物信息学预测表明，NSCLC中的肿瘤抑制基因肝癌缺失1（DLC-1）是miR-429的推定靶基因。因此，进行荧光素酶报告基因测定，并证实miR-429能够结合H1229细胞中DLC-1 mRNA的3 '非翻译区。在NSCLC H1229细胞中，过表达miR-429可抑制DLC-1蛋白的表达，而敲低miR-429可促进DLC-1蛋白的表达。此外，DLC-1的过表达不仅抑制H1229细胞增殖，而且还逆转了miR-429过表达对H1229细胞增殖的促进作用。基于这些发现，本研究表明，miR-429可能通过直接抑制NSCLC细胞中DLC-1蛋白表达而在调节细胞增殖中具有致癌作用。因此，miR-429可能是治疗NSCLC生长的假定治疗靶点。
The microRNA (miR)-200 family has been demonstrated to be associated with the tumorigenesis and progression of multiple types of human cancer, including non-small cell lung cancer (NSCLC). As a member of the miR-200 family, miR-429 was recently identified to have an oncogenic role in NSCLC. However, the role of miR-429 in NSCLC growth as well as the underlying mechanism remains to be fully elucidated. In the present study, NSCLC cell line H1229 was transfected with miR-429 mimic or inhibitor, respectively. It was observed that overexpression of miR-429 led to a significant increase in NSCLC cell proliferation, while knockdown of miR-429 suppressed the proliferation of H1229 cells. Bioinformatic prediction suggested that deleted in liver cancer 1 (DLC-1), a tumor suppressor in NSCLC, was a putative target gene of miR-429. Therefore, a luciferase reporter assay was performed and confirmed that miR-429 was able to bind the 3'-untranslated region of DLC-1 mRNA in H1229 cells. Furthermore, overexpression of miR-429 inhibited the protein expression of DLC-1, while knockdown of miR-429 promoted the protein expression of DLC-1 in NSCLC H1229 cells. In addition, overexpression of DLC-1 not only inhibited H1229 cell proliferation, but also additionally reversed the promoting effect of miR-429 overexpression on H1229 cell proliferation. Based on these findings, the present study suggests that miR-429 may have an oncogenic role in the regulation of cell proliferation via direct inhibition of DLC-1 protein expression in NSCLC cells. Therefore, miR-429 may present a putative therapeutic target for the treatment of NSCLC growth.