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含1个假基因Loc344887的类NmrA家族结构域在胆囊癌中扩增并促进上皮-间质转化。

The NmrA-like family domain containing 1 pseudogene Loc344887 is amplified in gallbladder cancer and promotes epithelial-mesenchymal transition.

作者信息

Wu Xiao-Cai, Wang Shou-Hua, Ou Hong-Hui, Zhu Bing, Zhu Yong, Zhang Qi, Yang Yang, Li Hua

机构信息

Department of Hepatic Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Tertiary Referral Center for Abdominal Surgery, Department of General Surgery, Shanghai Tenth People's Hospital Affiliated to Tongji University, Shanghai, China.

出版信息

Chem Biol Drug Des. 2017 Sep;90(3):456-463. doi: 10.1111/cbdd.12967. Epub 2017 Apr 11.

Abstract

The expression pattern and biological role of long non-coding RNA (lncRNA) in cancer has been reported to be involved in many cancers. Here, we report the expression and biological role of a newly discovered lncRNA NmrA-like family domain containing 1 pseudogene (Loc344887) in gallbladder cancer (GBC). In this study, we found that the expression of Loc344887 was significantly elevated in GBC tissues and cell lines when compared with matched normal tissues and normal epithelial bile duct cell line, respectively. High Loc344887 was associated with larger tumor size. Loc344887 was upregulated significantly after ectopic expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in GBC cells. Downregulation of Loc344887 in GBC cells suppressed cell proliferation, blocked cells in G0/S phase, and decreased the migration and invasion cell numbers. In addition, downregulation of Loc344887 decreased the expression of transcription factor Twist, mesenchymal marker Vimentin, and N-cadherin and increased the expression of epithelial maker E-cadherin, which could prompt a mesenchymal-to-epithelial transition phenotype. These results demonstrated that Loc344887 might contribute to cell proliferation and epithelial-to-mesenchymal transition process in GBC, which might be a potential therapeutic target.

摘要

据报道,长链非编码RNA(lncRNA)在癌症中的表达模式和生物学作用与多种癌症有关。在此,我们报告一种新发现的含NmrA样家族结构域1假基因(Loc344887)的lncRNA在胆囊癌(GBC)中的表达及生物学作用。在本研究中,我们发现与配对的正常组织和正常胆管上皮细胞系相比,Loc344887在GBC组织和细胞系中的表达显著升高。Loc344887高表达与更大的肿瘤大小相关。在GBC细胞中异位表达核因子(红系衍生2)样2(Nrf2)后,Loc344887显著上调。在GBC细胞中下调Loc344887可抑制细胞增殖,使细胞停滞于G0/S期,并减少迁移和侵袭的细胞数量。此外,下调Loc344887可降低转录因子Twist、间充质标志物波形蛋白和N-钙黏蛋白的表达,并增加上皮标志物E-钙黏蛋白的表达,这可促使间充质-上皮转化表型。这些结果表明,Loc344887可能促进GBC中的细胞增殖和上皮-间充质转化过程,可能是一个潜在的治疗靶点。

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