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小核仁RNA 78的上调与肝细胞癌的侵袭性表型和不良预后相关。

Up-regulation of small nucleolar RNA 78 is correlated with aggressive phenotype and poor prognosis of hepatocellular carcinoma.

作者信息

Ma Pei, Wang Haitao, Han Lu, Jing Wei, Zhou Xin, Liu Zhisu

机构信息

Center for Gene Diagnosis, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, China.

Department of Hepatobiliary and Pancreas, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, China.

出版信息

Tumour Biol. 2016 Dec;37:15753–15761. doi: 10.1007/s13277-016-5366-6. Epub 2016 Oct 21.

Abstract

Small nucleolar RNAs (snoRNAs) as a novel molecular species may have significant and comprehensive influences on the development and progression of hepatocellular carcinoma (HCC). We recently characterized snoRNA transcriptome signatures in HCC tissues by small RNA sequencing and found that small nucleolar RNA 78 (SNORD78) was associated with HCC. However, little is known about the pathological role of SNORD78 in HCC patients. This study aimed to profile SNORD78 expression signature and then to explore the pathogenesis of SNORD78 in HCC. The real-time PCR results showed that SNORD78 was greatly upregulated in HCC tissues than adjacent noncancerous tissues (p = 0.004). Correlation analysis showed that high-level expression of SNORD78 was notably associated with tumor number (single vs. multiply, p = 0.02), stage (I∼II vs. III∼IV, p = 0.014), and distant metastasis (absent vs. present, p = 0.01) in HCC patients. Univatiate and multivariate analyses showed that SNORD78 was a significant prognostic predictor for overall survival and recurrence-free survival of HCC patients (hazard ratio = 1.375, 95 % CI = 1.125-1.680, p = 0.002; hazard ratio = 1.418, 95 % CI = 1.201-1.675, p < 0.001). Moreover, Kaplan-Meier analysis showed that high-level expression of SNORD78 was associated with short overall survival and recurrence-free survival of HCC patients (p = 0.023, 0.014). Functionally, knockdown of SNORD78 significantly inhibited cellular proliferation, migration, and invasion of SK-Hep-1 via inducing G0/G1 cell cycle arrest and apoptosis. In conclusion, SNORD78 may be associated with aggressive phenotype and poor prognosis of HCC.

摘要

小核仁RNA(snoRNAs)作为一种新型分子种类,可能对肝细胞癌(HCC)的发生发展具有重大而全面的影响。我们最近通过小RNA测序对HCC组织中的snoRNA转录组特征进行了表征,发现小核仁RNA 78(SNORD78)与HCC相关。然而,关于SNORD78在HCC患者中的病理作用知之甚少。本研究旨在分析SNORD78的表达特征,进而探讨其在HCC中的发病机制。实时PCR结果显示,SNORD78在HCC组织中的表达明显高于相邻的非癌组织(p = 0.004)。相关性分析表明,HCC患者中SNORD78的高水平表达与肿瘤数量(单发与多发,p = 0.02)、分期(I~II期与III~IV期,p = 0.014)及远处转移(无与有,p = 0.01)显著相关。单因素和多因素分析表明,SNORD78是HCC患者总生存和无复发生存的重要预后预测指标(风险比 = 1.375,95%可信区间 = 1.125 - 1.680,p = 0.002;风险比 = 1.418,95%可信区间 = 1.201 - 1.675,p < 0.001)。此外,Kaplan-Meier分析显示,SNORD78的高水平表达与HCC患者较短的总生存和无复发生存相关(p = 0.023,0.014)。在功能上,敲低SNORD78可通过诱导G0/G1期细胞周期阻滞和凋亡,显著抑制SK-Hep-1细胞的增殖、迁移和侵袭。总之,SNORD78可能与HCC的侵袭性表型和不良预后相关。

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