Wang Hui, Yu Liang, Shan Xiujuan
Department of Dermatology, Weifang People's Hospital, Weifang, Shandong 261041, P.R. China.
Department of Clinical Laboratory, Weifang People's Hospital, Weifang, Shandong 261041, P.R. China.
Mol Med Rep. 2017 Jun;15(6):3852-3858. doi: 10.3892/mmr.2017.6468. Epub 2017 Apr 12.
Melanoma has the highest fatality and malignancy of all skin cancers. In cancer, microRNAs (miRNAs) act as tumor suppressors or oncogenes, and inactivation of oncogenic miRNAs or restoration of tumor suppressor miRNAs has potential for cancer treatment. In the present study, miR‑455 expression levels were examined in melanoma tissues and cell lines, and miR‑455 was significantly downregulated in melanoma compared with matched normal tissues or normal epidermal melanocytes. In addition, increasing miR‑455 expression in melanoma cells reduced cell proliferation and invasion. Bioinformatic analysis revealed that insulin‑like growth factor 1 receptor (IGF‑1R) was a putative target of miR‑455. Luciferase reporter assays, reverse transcription‑quantitative polymerase chain reaction and western blot confirmed that miR‑455 targeted the 3'‑untranslated region of IGF‑1R and thus regulated the biological processes of melanoma cells. IGF‑1R knockdown resulted in similar effects as miR‑455 overexpression in melanoma cells. In summary, these findings indicated that miR‑455 was downregulated in melanoma, and inhibited proliferation and invasion of melanoma cells through directly targeting IGF‑1R. This also suggested that the restoration of miR‑455 may be worth investigation as a therapeutic treatment for patients with melanoma.
黑色素瘤是所有皮肤癌中致死率和恶性程度最高的。在癌症中,微小RNA(miRNA)可作为肿瘤抑制因子或致癌基因,使致癌性miRNA失活或恢复肿瘤抑制性miRNA的功能具有癌症治疗潜力。在本研究中,检测了黑色素瘤组织和细胞系中miR-455的表达水平,与匹配的正常组织或正常表皮黑素细胞相比,黑色素瘤中miR-455显著下调。此外,增加黑色素瘤细胞中miR-455的表达可降低细胞增殖和侵袭能力。生物信息学分析显示,胰岛素样生长因子1受体(IGF-1R)是miR-455的一个假定靶点。荧光素酶报告基因检测、逆转录-定量聚合酶链反应和蛋白质印迹证实,miR-455靶向IGF-1R的3'-非翻译区,从而调节黑色素瘤细胞的生物学过程。在黑色素瘤细胞中,敲低IGF-1R产生的效果与过表达miR-455相似。总之,这些发现表明,miR-455在黑色素瘤中表达下调,并通过直接靶向IGF-1R抑制黑色素瘤细胞的增殖和侵袭。这也表明,恢复miR-455的表达可能值得作为黑色素瘤患者的一种治疗方法进行研究。