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GRHL3基因敲低可抑制人结肠癌细胞的活性,并诱导其细胞周期阻滞和凋亡。

Knockdown of GRHL3 inhibits activities and induces cell cycle arrest and apoptosis of human colorectal cancer cells.

作者信息

Wang Xiao-Kang, Zhou Fen-Fang, Tao Hao-Ran, Wang Xin, Zhang Chi, Su Fei, Wang Shi-Pei, Xu Li-Hua, Pan Xue-Kai, Feng Mao-Hui, Xie Wei

机构信息

Department of Oncology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.

School of Clinical Medicine, Fenyang Medical College, Shanxi Medical University, Fenyang, 032200, China.

出版信息

J Huazhong Univ Sci Technolog Med Sci. 2017 Dec;37(6):880-885. doi: 10.1007/s11596-017-1821-x. Epub 2017 Dec 21.

Abstract

The Grainyhead-like 3 (GRHL3) is involved in epidermal barrier formation, neural tube closure and wound repair. Previous studies have suggested that GRHL3 has been linked to many different types of cancers. However, to date, its effects on human colorectal cancer (CRC) has not been clarified yet. Our microarray analysis has indicated predominant GRHL3 expression in CRC. The purpose of this study was to investigate the expression and significance of GRHL3 in CRC tumorigenesis using CRC tissues and paired paracancerous tissues, as well as using distinct CRC cell lines (HT29 and DLD1). We observed increased GRHL3 expression at both mRNA and protein levels in CRC tissues and CRC cell lines using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. Moreover, silencing GRHL3 with siRNA could suppress CRC cell proliferation, viability and migration in vitro. We also found that knockdown of GRHL3 could promote cell cycle arrest at G/G phase in HT29 cells and DLD1 cells, and induce cell apoptosis in HT29 cells. Together, our study revealed the down-regulation of GRHL3 in vitro could inhibit CRC cell activity and trigger cell cycle arrest at G/G phase and apoptosis.

摘要

颗粒头样蛋白3(GRHL3)参与表皮屏障形成、神经管闭合和伤口修复。先前的研究表明,GRHL3与多种不同类型的癌症有关。然而,迄今为止,其对人类结直肠癌(CRC)的影响尚未阐明。我们的微阵列分析表明GRHL3在CRC中呈优势表达。本研究的目的是利用CRC组织和配对的癌旁组织以及不同的CRC细胞系(HT29和DLD1),研究GRHL3在CRC肿瘤发生中的表达及意义。我们使用定量实时聚合酶链反应(qRT-PCR)和蛋白质免疫印迹法观察到CRC组织和CRC细胞系中GRHL3在mRNA和蛋白质水平上的表达均增加。此外,用小干扰RNA(siRNA)沉默GRHL3可在体外抑制CRC细胞增殖、活力和迁移。我们还发现,敲低GRHL3可促进HT29细胞和DLD1细胞在G / G期的细胞周期阻滞,并诱导HT29细胞凋亡。总之,我们的研究表明,体外下调GRHL3可抑制CRC细胞活性,并触发细胞在G / G期的细胞周期阻滞和凋亡。

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