Yu Ming Jun, Zhao Na, Shen Haibin, Wang Haiming
Department of Surgery, Hangzhou Third Hospital , Hangzhou, China .
Genet Test Mol Biomarkers. 2018 Nov;22(11):656-663. doi: 10.1089/gtmb.2018.0151.
Gastric cancer (GC) is one of the most prevalent malignant tumors displaying both high incidence and mortality throughout much of the world. Recently, long noncoding RNAs (lncRNAs) have been implicated in the development and progression of GC.
In the present study, we investigated the biological function and molecular mechanisms of lncRNA MRPL39 in GC.
We found that MRPL39 was significantly downregulated in GC tissues and cell lines and that its expression level was negatively associated with carcinoma size, tumor, lymph node, metastasis (TNM) stage, and lymphatic metastasis. Patients with low MRPL39 expression levels revealed a short overall and disease-free survival period. Over-expression of MRPL39 in the GC cell lines BGC823 and SGC-7901 inhibited cell growth, proliferation, migration, and invasion. MiR-130, a putative target gene of MRPL39, displayed an inverse association with the expression of MRPL39 in GC tissues and cell lines. Moreover, a luciferase assay demonstrated a direct binding between the miR-130 and MRPL39, and the reintroduction of miR-130 abrogated the anti-tumor effect of MRPL39 on GC cells.
Taken together, these findings indicate that MRPL39 serves as a tumor suppressor by directly targeting miR-130 in GC, which suggests that it might be a novel biomarker in the diagnosis and prognosis of GC.
胃癌(GC)是世界上许多地区发病率和死亡率都很高的最常见恶性肿瘤之一。最近,长链非编码RNA(lncRNAs)已被证明与胃癌的发生和发展有关。
在本研究中,我们调查了lncRNA MRPL39在胃癌中的生物学功能和分子机制。
我们发现MRPL39在胃癌组织和细胞系中显著下调,其表达水平与肿瘤大小、肿瘤、淋巴结、转移(TNM)分期和淋巴转移呈负相关。MRPL39表达水平低的患者总生存期和无病生存期较短。在胃癌细胞系BGC823和SGC-7901中过表达MRPL39可抑制细胞生长、增殖、迁移和侵袭。MRPL39的假定靶基因miR-130在胃癌组织和细胞系中的表达与MRPL39呈负相关。此外,荧光素酶报告基因检测证明miR-130与MRPL39直接结合,重新导入miR-130可消除MRPL39对胃癌细胞的抗肿瘤作用。
综上所述,这些发现表明MRPL39在胃癌中通过直接靶向miR-130发挥肿瘤抑制作用,这表明它可能是胃癌诊断和预后的一种新型生物标志物。