Wang Junqing, Chen Xuehua, Su Liping, Li Pu, Cai Qu, Liu Bingya, Wu Weize, Zhu Zhenggang
Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, 197, Rui Jin Er Road, Shanghai 20025, People's Republic of China; Shanghai Key Laboratory of Gastric Neoplasms, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, 197, Rui Jin Er Road, Shanghai 20025, People's Republic of China; Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, 197, Rui Jin Er Road, Shanghai 20025, People's Republic of China.
Shanghai Key Laboratory of Gastric Neoplasms, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, 197, Rui Jin Er Road, Shanghai 20025, People's Republic of China; Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, 197, Rui Jin Er Road, Shanghai 20025, People's Republic of China.
Biomed Pharmacother. 2015 May;72:66-73. doi: 10.1016/j.biopha.2015.04.001. Epub 2015 Apr 14.
MicroRNA-126 (miR-126) is a pivotal post-transcriptional regulator, which has been validated as a suppressor in gastric cancer (GC). However, the downstream of its tumor inhibiting function has not been totally clear. L-type amino-acid transporter 1 (LAT-1) is a novel member of system L-type transporters involving in cell proliferation, and we have previously validated that LAT-1 played a role of promotor in GC. In this study, we further detected and confirmed that LAT-1 was exactly targeted by miR-126 in GC. We found LAT-1 was significantly downregulated in GC MKN-45 cell lines by using miR-126 mimics, along with an impairment on cell proliferation and cell cycle. Additionally, by overexpressing LAT-1 in MKN-45 cells which was firstly treated with miR-126 mimics, the ability of cell proliferation in MKN-45 cells was definitely rescued. Thus, our results suggests and consolidates the standpoint that miR-126 plays a pivotal role in GC suppressing the process of GC cell, and this function is at least partly taken to implement by miR-126s's post-transcriptional effect on LAT-1. This might provide us likely potential biomarkers and targets for GC prevention, diagnosis and therapeutic treatment.
微小RNA-126(miR-126)是一种关键的转录后调节因子,已被证实为胃癌(GC)的抑制因子。然而,其肿瘤抑制功能的下游机制尚未完全明确。L型氨基酸转运蛋白1(LAT-1)是L型转运体系统的一个新成员,参与细胞增殖,我们之前已经证实LAT-1在胃癌中起促进作用。在本研究中,我们进一步检测并证实LAT-1在胃癌中确实是miR-126的靶标。我们发现,使用miR-126模拟物可使胃癌MKN-45细胞系中的LAT-1显著下调,同时细胞增殖和细胞周期也受到损害。此外,在先用miR-126模拟物处理的MKN-45细胞中过表达LAT-1,可明显挽救MKN-45细胞的增殖能力。因此,我们的结果表明并巩固了这样的观点,即miR-126在胃癌抑制GC细胞过程中起关键作用,且该功能至少部分是通过miR-126对LAT-1的转录后作用来实现的。这可能为我们提供用于胃癌预防、诊断和治疗的潜在生物标志物和靶点。