Chen Qian, Yang Zhen, Pan Gaofeng, Ding Hongjian, Jiang Daowen, Huang Jianfang, Liu Weiyan
Department of General Surgery, Minhang Hospital, Fudan University No. 170, Xinsong Road, Minhang District Shanghai 201199 China
Department of Infection Diseases, The Fifth People's Hospital Affiliated to Fudan University Shanghai 201199 China
RSC Adv. 2018 Jul 19;8(46):26020-26028. doi: 10.1039/c8ra02722f.
MicroRNAs (miRNAs) are small noncoding RNAs that are known to participate in the regulation of many physiological and pathological processes, which can indirectly influence the development of malignant behaviors. Numerous studies have demonstrated that miR-449a plays important roles in human carcinogenesis. However, its precise functional and regulatory roles remain unclear. In this study, we mainly explored the functional role of miR-449a in gastric cancer (GC). The expression levels of miR-449a in 98 cases of GC tissues and cell lines were determined by qRT-PCR. The possible mechanisms of miR-449a in GC cells were explored by fluorescence reporter assay. miR-449a expression was significantly lower in GC tissues compared to matched para-carcinoma tissues and was associated with tumor differentiation. Furthermore, knockdown of miR-449a by siRNA significantly inhibited MKN-28 cell proliferation, migration and invasion as well as tumorigenesis inducing G0/G1 arrest of GC cells. In addition, we identified SGPL1 as a target of miR-449a and demonstrated that miR-449a regulated SGPL1 expression binding its 3'-UTR region. The experiments indicated that miR-449a functions as a novel tumor suppressor in GC and its anti-oncogenic activity may involve its inhibition of the target gene SGPL1. These findings suggested that miR-449a may be a promising candidate for the development of antitumor drugs targeting GC.
微小RNA（miRNA）是一类小的非编码RNA，已知其参与许多生理和病理过程的调控，可间接影响恶性行为的发展。大量研究表明，miR-449a在人类致癌过程中发挥重要作用。然而，其确切的功能和调控作用仍不清楚。在本研究中，我们主要探讨了miR-449a在胃癌（GC）中的功能作用。通过qRT-PCR检测了98例GC组织和细胞系中miR-449a的表达水平。通过荧光报告基因检测探讨了miR-449a在GC细胞中的可能机制。与配对的癌旁组织相比，miR-449a在GC组织中的表达显著降低，且与肿瘤分化相关。此外，用siRNA敲低miR-449a可显著抑制MKN-28细胞的增殖、迁移和侵袭以及肿瘤发生，诱导GC细胞G0/G1期阻滞。此外，我们鉴定出SGPL1是miR-449a的一个靶标，并证明miR-449a通过结合其3'-UTR区域来调节SGPL1的表达。实验表明，miR-449a在GC中作为一种新型肿瘤抑制因子发挥作用，其抗肿瘤活性可能涉及其对靶基因SGPL1的抑制。这些发现提示，miR-449a可能是开发针对GC的抗肿瘤药物的一个有前景的候选分子。
