Long Noncoding RNA HOTAIR Controls Cell Cycle by Functioning as a Competing Endogenous RNA in Esophageal Squamous Cell Carcinoma.
Long Noncoding RNA HOTAIR Controls Cell Cycle by Functioning as a Competing Endogenous RNA in Esophageal Squamous Cell Carcinoma.
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DOI：
10.1016/j.tranon.2016.09.005
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发表时间：
2016-12
影响因子：
5
通讯作者：
Han, Xinwei
中科院分区：
文献类型：
--
作者：
Ren, Kewei;Li, Yahua;Lu, Huibin;Li, Zongming;Li, Zhen;Wu, Kai;Li, Zhiqin;Han, Xinwei
最近的研究表明，长非编码RNA(LncRNAs)在包括食管鳞状细胞癌(ESCC)在内的肿瘤的发生和发展中起着关键作用。据报道，lncRNA HOX转录反义RNA(HOTAIR)表达异常，与ESCC的发生发展密切相关。然而，HOTAIR在ESCC发生发展中的生物学作用和潜在机制仍不清楚。在此，我们发现HOTAIR在ESCC细胞中异常上调，HOTAIR缺失抑制了ESCC细胞的增殖并导致G1期细胞周期停滞。此外，我们还发现HOTAIR通过直接与miR-1结合，作为内源性海绵下调miR-1的表达。此外，HOTAIR逆转了miR-1对ESCC细胞增殖和细胞周期的影响，这涉及到miR-1靶点细胞周期蛋白D1(CCND1)的表达下调。综上所述，我们的研究阐明了一个新的HOTAIR/miR-1/CCND1调控轴，HOTAIR通过海绵包裹miR-1并上调CCND1的表达，发挥竞争内源性RNA的作用，从而促进食管癌的发生。对该途径的研究有助于更好地了解食管鳞癌的发病机制，并有助于开展针对食管鳞癌的靶向治疗。
Recent studies have shown that long noncoding RNAs (lncRNAs) play pivotal roles in the initiation and progression of cancer, including esophageal squamous cell carcinoma (ESCC). The lncRNA HOX transcript antisense RNA (HOTAIR) was reported to be dysregulated and correlated with the progression of ESCC. However, the biological role and the underlying mechanism of HOTAIR in the development of ESCC remain unclear. Herein, we found that HOTAIR was aberrantly upregulated in ESCC cells and that HOTAIR depletion inhibited proliferation and led to G1 cell cycle arrest in ESCC cells. Besides, we found that HOTAIR acted as an endogenous sponge to downregulate miR-1 expression by directly binding to miR-1. Furthermore, HOTAIR overturned the effect of miR-1 on the proliferation and cell cycle profile in ESCC cells, which involved the derepression of cyclin D1 (CCND1) expression, a target of miR-1. Taken together, our study elucidated a novel HOTAIR /miR-1/CCND1 regulatory axis in which HOTAIR acted as a competing endogenous RNA by sponging miR-1 and upregulated CCND1 expression, thereby facilitating the tumorigenesis of ESCC. Investigation of this lncRNA/miRNA/mRNA pathway may contribute to a better understanding of ESCC pathogenesis and facilitate the development of lncRNA-directed therapy against this disease.
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影响因子：
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作者：
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影响因子：
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