Upregulated expression of long non-coding RNA LINC00982 regulates cell proliferation and its clinical relevance in patients with gastric cancer
Upregulated expression of long non-coding RNA LINC00982 regulates cell proliferation and its clinical relevance in patients with gastric cancer
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DOI：
10.1007/s13277-015-3979-9
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发表时间：
2016-02-01
期刊：
影响因子：
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通讯作者：
Xie, Cong-ying
中科院分区：
文献类型：
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作者：
Fei, Zheng-hua;Yu, Xiao-juan;Xie, Cong-ying
新的证据表明，长链非编码RNA（lncRNA）的异常表达与肿瘤的发生、发展密切相关，可能成为肿瘤诊断和预后的生物标志物或潜在的治疗靶点。因此，鉴定癌症相关lncRNA并研究其生物学功能和分子机制对于理解癌症的发生和发展具有重要意义。在本研究中，我们发现了一种新的lncRNA LINC 00982，其在106例胃癌（GC）组织中的表达与癌旁正常组织相比明显下调（P < 0.001）。LINC 00982的表达与胃癌浸润深度（P < 0.001）、TNM分期（P = 0.004）和淋巴结转移（P = 0.005）呈负相关。LINC 00982水平在区分胃癌组织与对照中是稳健的[曲线下面积（AUC）= 0.742; 95%置信区间（CI）= 0.678-0.800，P < 0.01]。Kaplan-Meier分析显示，LINC 00982表达降低导致患者的总生存率（P < 0.01）和无病生存率（P < 0.01）降低。多变量生存分析也表明LINC 00982可能是一个独立的预后标志物。胃癌患者胃液中LINC 00982的水平显著低于正常人（P = 0.026）。siRNA敲低LINC 00982表达可促进胃癌细胞增殖和细胞周期进程，而LINC 00982异位表达可抑制胃癌细胞增殖，部分通过调节P15和P16蛋白表达而使胃癌细胞周期阻滞。我们的研究结果表明，lncRNA LINC 00982的减少可以被确定为GC中预后不良的生物标志物，并调节细胞增殖。
Emerging evidences indicate that dysregulated long non-coding RNAs (lncRNAs) are implicated in cancer tumorigenesis and progression and might be used as diagnosis and prognosis biomarker or potential therapeutic targets. Therefore, identification of cancer-associated lncRNAs and investigation of their biological functions and molecular mechanisms are important for understanding the development and progression of cancer. In this study, we identified a novel lncRNA LINC00982, whose expression was downregulated in tumor tissues in 106 patients with gastric cancer (GC) compared with those in the adjacent normal tissues (P < 0.001). Furthermore, decreased LINC00982 expression was negatively correlated with invasion depth (P < 0.001), advanced TNM stage (P = 0.004), and regional lymph node metastasis (P = 0.005). LINC00982 levels were robust in differentiating gastric cancer tissues from controls [area under the curve (AUC) = 0.742; 95 % confidence interval (CI) = 0.678-0.800, P < 0.01]. Kaplan-Meier analysis demonstrated that decreased LINC00982 expression contributed to poor overall survival (P < 0.01) and disease-free survival (P < 0.01) of patients. A multivariate survival analysis also indicated that LINC00982 could be an independent prognostic marker. The levels of LINC00982 in gastric juice from gastric patients were significantly lower than those from normal subjects (P = 0.026). Furthermore, knockdown of LINC00982 expression by small interfering RNA (siRNA) could promote cell proliferation and cell cycle progression, while ectopic expression of LINC00982 inhibited cell proliferation and rendered cell cycle arrest in GC cells partly via regulating P15 and P16 protein expressions. Our findings present that decreased lncRNA LINC00982 could be identified as a poor prognostic biomarker in GC and regulate cell proliferation.