Pu Wei, Shang Yongming, Shao Qiang, Yuan Xinpeng
Department of Dermatology, The Central Hospital of Zibo, Zibo, Shandong 255000, P.R. China.
Department of Dermatology, Zibo Traditional Chinese Medicine Hospital, Zibo, Shandong 255300, P.R. China.
Oncol Lett. 2018 May;15(5):7111-7117. doi: 10.3892/ol.2018.8172. Epub 2018 Mar 5.
Previous studies have explored the functions of microRNA (miR)-146a in different types of cancer through mediating different targets. However, the roles of miR-146a in malignant melanoma (MM) cell migration and invasion remain largely elusive. In the present study, the potential molecular function of miR-146a in MM was investigated. Reverse transcription-quantitative polymerase chain reaction was utilized to detect miR-146a expression in MM tissues and cell lines. A Transwell assay was performed to confirm the ability of migration and invasion. A luciferase assay and biological analysis were used to predict and determine the targets of miR-146a. The expression of miR-146a was upregulated in melanoma tissues and cell lines. Clinicopathological analysis indicated that the miR-146a level was negatively correlated with the progression of melanoma. Abnormal expression of miR-146a promoted cell migration and invasion in MM cells. Additionally, it was also observed that Mothers against decapentaplegic homolog 4 (SMAD4) was a novel target of miR-146a in MM. SMAD4 was negatively associated with miR-146a in MM and abnormal expression of SMAD4 attenuated miR-146a-mediated promotion of cell migration and invasion. In conclusion, miR-146a functioned as an oncogene by directly targeting SMAD4 and it may be a novel diagnostic and therapeutic marker of MM.
以往的研究通过介导不同靶点探索了微小RNA（miR）-146a在不同类型癌症中的功能。然而，miR-146a在恶性黑色素瘤（MM）细胞迁移和侵袭中的作用仍 largely难以捉摸。在本研究中，研究了miR-146a在MM中的潜在分子功能。利用逆转录定量聚合酶链反应检测MM组织和细胞系中miR-146a的表达。进行Transwell试验以确认迁移和侵袭能力。使用荧光素酶试验和生物学分析来预测和确定miR-146a的靶点。miR-146a在黑色素瘤组织和细胞系中表达上调。临床病理分析表明，miR-146a水平与黑色素瘤的进展呈负相关。miR-146a的异常表达促进了MM细胞的迁移和侵袭。此外，还观察到，抗五肢瘫同源蛋白4（SMAD4）是MM中miR-146a的一个新靶点。在MM中，SMAD4与miR-146a呈负相关，SMAD4的异常表达减弱了miR-146a介导的细胞迁移和侵袭促进作用。总之，miR-146a通过直接靶向SMAD4发挥癌基因作用，它可能是MM的一种新的诊断和治疗标志物。
