Mao Yu, Liu Jia, Zhang Dakai, Li Baosheng
Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China; Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, China.
Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, China; School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, Jinan, China.
Biomed Pharmacother. 2015 Dec;76:82-93. doi: 10.1016/j.biopha.2015.10.005. Epub 2015 Nov 10.
The nuclear factor I/X (NFIX) plays important roles in cell differentiation, but its function in cancer is still unclear. Besides, accumulating studies reported the important role of microRNAs (miRNAs) in the regulation of gene expression, among of which, the miR-1290 has been widely reported in various cancers. In this study, we investigated the mechanism through which NFIX was regulated by miRNAs. Firstly, we found that the NFIX protein and mRNA levels were consistently down-regulated in ESCC tissues suggesting that a post-transcriptional mechanism maybe involved in the regulation of NFIX. Since microRNAs (miRNAs) are powerful post-transcriptional regulators of gene expression, we performed bioinformatic analyses to search for miRNAs that potentially target NFIX. We identified the specific targeting site of miR-1290 in the 3'-UTR of NFIX and the inverse correlation between the levels of miR-1290 and NFIX protein and mRNA in ESCC tissue samples was then confirmed. By overexpressing or silencing miR-1290 in ESCC cells, we experimentally validated that miR-1290 directly binds to the 3'-UTR of the NFIX transcript and degrade the NFIX mRNA to regulate NFIX expression. Furthermore, the biological consequences that miR-1290 mediated by targeting NFIX were examined in vitro. We demonstrated that miR-1290 could promote proliferation, migration and invasion via the negative regulation of NFIX expression. Taken together, our findings suggested that miR-1290 functions as a tumor oncogene in the progression of ESCC by targeting NFIX.
核因子I/X（NFIX）在细胞分化中发挥重要作用，但其在癌症中的功能仍不清楚。此外，越来越多的研究报道了微小RNA（miRNA）在基因表达调控中的重要作用，其中，miR-1290在多种癌症中已有广泛报道。在本研究中，我们探究了miRNA调控NFIX的机制。首先，我们发现NFIX蛋白和mRNA水平在食管癌组织中持续下调，这表明转录后机制可能参与了NFIX的调控。由于微小RNA（miRNA）是基因表达强大的转录后调节因子，我们进行了生物信息学分析以寻找可能靶向NFIX的miRNA。我们确定了miR-1290在NFIX 3'-UTR中的特异性靶向位点，随后证实了食管癌组织样本中miR-1290水平与NFIX蛋白和mRNA水平呈负相关。通过在食管癌细胞中过表达或沉默miR-1290，我们通过实验验证了miR-1290直接与NFIX转录本的3'-UTR结合并降解NFIX mRNA以调节NFIX表达。此外，我们在体外研究了miR-1290靶向NFIX所介导的生物学后果。我们证明miR-1290可通过对NFIX表达的负调控促进增殖、迁移和侵袭。综上所述，我们的研究结果表明，miR-1290在食管癌进展中通过靶向NFIX发挥肿瘤癌基因的作用。
