Wang Tianxi, Zhang Jun, Tian Jingjing, Hu Shasha, Wei Rongna, Cui Lihong
Department of Gastroenterology, Tianjin Nankai Hospital, Nankai, Tianjin 300100, P.R. China.
Department of General Medicine, Tianjin Beichen Hospital, Tianjin, 300401, P.R. China.
Oncol Lett. 2019 Jul;18(1):629-636. doi: 10.3892/ol.2019.10390. Epub 2019 May 21.
MicroRNAs (miRNAs/miRs) offer great potential as biomarkers for the early detection and prognosis of cancer, and the discovery of miRNAs associated with gastric cancer is required. In the present study, the differences in the plasma expression levels of miR-141 between patients with gastric cancer and healthy controls, and the role of miR-141 in gastric cancer cell oncogenesis were investigated. A follow-up study of 164 patients with gastric cancer who underwent tumor resection was conducted, and comparisons with healthy control subjects were drawn. To investigate the biological functions of miR-141, a series of and assays were conducted, including proliferation, wound-healing and Transwell assays, and a xenograft tumor model. The results demonstrated that miR-141 expression was significantly decreased in tumor tissues compared with in healthy tissues (P<0.05). Kaplan-Meier analysis revealed improved survival benefits with increased miR-141 expression (as determined using the log-rank test, P<0.001), and multivariate Cox regression analysis revealed that patients with decreased expression levels of miR-141 carried a greater risk of death (hazard ratio=2.352; 95% CI=1.379-4.012; P=0.002). The downregulation of miR-141 was also associated with WHO staging, particularly for lymph node and distant metastasis. Exogenous overexpression of miR-141 significantly inhibited the proliferative and migratory abilities of the gastric cancer cell line BGC-823. studies also demonstrated that exogenous overexpression of miR-141 in BGC-823 cells markedly reduced tumor growth in nude mice. The present study revealed that increased miR-141 expression may be a positive prognostic factor, which may be clinically beneficial in patients with gastric cancer.
微小RNA(miRNA/miR)作为癌症早期检测和预后的生物标志物具有巨大潜力,因此需要发现与胃癌相关的miRNA。在本研究中,调查了胃癌患者与健康对照者血浆中miR-141表达水平的差异,以及miR-141在胃癌细胞发生过程中的作用。对164例行肿瘤切除术的胃癌患者进行了随访研究,并与健康对照者进行了比较。为了研究miR-141的生物学功能,进行了一系列实验,包括增殖、伤口愈合和Transwell实验,以及异种移植肿瘤模型。结果表明,与健康组织相比,肿瘤组织中miR-141的表达显著降低(P<0.05)。Kaplan-Meier分析显示,随着miR-141表达增加,生存获益改善(使用对数秩检验确定,P<0.001),多因素Cox回归分析显示,miR-141表达水平降低的患者死亡风险更高(风险比=2.352;95%置信区间=1.379-4.012;P=0.002)。miR-141的下调也与世界卫生组织(WHO)分期相关,特别是与淋巴结和远处转移有关。miR-141的外源性过表达显著抑制了胃癌细胞系BGC-823的增殖和迁移能力。研究还表明,在BGC-823细胞中外源性过表达miR-141可显著降低裸鼠体内肿瘤的生长。本研究表明,miR-141表达增加可能是一个积极的预后因素,这可能对胃癌患者具有临床益处。