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长链非编码RNA FAM83H-AS1与结直肠癌的预后相关,并通过靶向Notch信号通路促进细胞增殖。

lncRNA FAM83H-AS1 is associated with the prognosis of colorectal carcinoma and promotes cell proliferation by targeting the Notch signaling pathway.

作者信息

Lu Song, Dong Wei, Zhao Pei, Liu Zhenjun

机构信息

ICU of Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 610041, P.R. China.

出版信息

Oncol Lett. 2018 Feb;15(2):1861-1868. doi: 10.3892/ol.2017.7520. Epub 2017 Dec 5.

Abstract

The long non-coding RNA, FAM83H antisense RNA 1 (head to head) (FAM83H-AS1), has exhibited a functional role as an oncogene in a number of different types of cancer. The aim of the present study was to reveal the dysregulation of FAM83H-AS1 in colorectal carcinoma (CRC) samples and elucidate its underlying associations with the Notch signaling pathway. The expression profiles of FAM83H-AS1 and two Notch signaling-associated molecules, Notch1 and Hes family basic-helix-loop-helix transcription factor 1 (Hes1), were measured by reverse transcription-polymerase chain reaction and western blot analysis. The Pearson χ test was employed to evaluate the associations between FAM83H-AS1 expression and clinical features. A statistically significant positive association between the expression levels of FAM83H-AS1 and those of Notch1 or Hes1 in CRC tissues was analyzed by Spearman's correlation analysis. The Kaplan-Meier method was used to compare the overall survival curves between the highly-expressed and low-expressed FAM83H-AS1 groups via a log-rank test. Specific small hairpin RNA was transfected to silence endogenous FAM83H-AS1. MTT and colony formation assays were performed to measure the growth-inhibition effect of silenced FAM83H-AS1. The levels of FAM83H-AS1, Notch1 and Hes1 were significantly increased in CRC samples and cell lines. Cell proliferation was markedly inhibited when FAM83H-AS1 was knocked down and this effect mediated by FAM83H-AS1 could be reversed by Notch1 regulators. Thus, downregulated FAM83H-AS1 exhibited an anti-proliferative role in CRC by repressing the Notch signaling pathway.

摘要

长链非编码RNA,FAM83H反义RNA 1(头对头)(FAM83H-AS1),在多种不同类型的癌症中已表现出作为癌基因的功能作用。本研究的目的是揭示FAM83H-AS1在结直肠癌(CRC)样本中的失调情况,并阐明其与Notch信号通路的潜在关联。通过逆转录-聚合酶链反应和蛋白质印迹分析来检测FAM83H-AS1以及两种与Notch信号相关的分子Notch1和Hes家族碱性螺旋-环-螺旋转录因子1(Hes1)的表达谱。采用Pearson χ检验来评估FAM83H-AS1表达与临床特征之间的关联。通过Spearman相关性分析来分析CRC组织中FAM83H-AS1表达水平与Notch1或Hes1表达水平之间的统计学显著正相关。使用Kaplan-Meier方法通过对数秩检验比较高表达和低表达FAM83H-AS1组之间的总生存曲线。转染特异性小发夹RNA以沉默内源性FAM83H-AS1。进行MTT和集落形成试验以测量沉默FAM83H-AS1的生长抑制作用。CRC样本和细胞系中FAM83H-AS1、Notch1和Hes1的水平显著升高。当FAM83H-AS1被敲低时,细胞增殖受到明显抑制,并且由FAM83H-AS1介导的这种作用可被Notch1调节剂逆转。因此,下调的FAM83H-AS1通过抑制Notch信号通路在CRC中发挥抗增殖作用。

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