Fujian Provincial Key Laboratory of Environment factors and Cancer, School of Public Health, Fujian Medical University, 1 Xuefubei Road, Fuzhou, Fujian, 350108, People's Republic of China.
Department of Epidemiology and Health Statistic, School of Public Health, Fujian Medical University, 1 Xuefubei Road, Fuzhou, Fujian, China.
BMC Cancer. 2018 Sep 15;18(1):894. doi: 10.1186/s12885-018-4804-9.
Pseudogenes are RNA transcripts with high homology with its parent protein-coding genes. Although pseudogenes lost the ability to produce protein, it still exert import biological function, and play important role in the pathogenesis of a wide varity of tumors; However, the role of pseudogenes in esophageal squamous cell carcinoma (ESCC) is poorly understood.
TUSC2P function in ESCC were explored using both in vitro and in vivo experiments cell proliferation, invasion and apoptosis assay was performed to evaluated the effect of TUSC2P on the tumor biology of ESCC. Expression of relative genes was assessed by quantitative real-time PCR (qRT-PCR) and western blotting in EC109 and TE-1 cell, as well as ESCC patients. 3'UTR luciferase assay was used to confirm the direct binding of miRNAs with TUSC2 and TUSC2P 3'UTR. Relation betweenTUSC2P, TUSC2 and ESCC prognosis was predicted by survival analysis (n = 56).
Pseudogene TUSC2P was down regulated in ESCC tissues compared with paired normal adjacent tissues, and the expression of TUSC2P was significantly correlated with survivalof ESCC patients. Over expression of TUSC2P in EC109 and TE-1 cells resulted in altered expression of TUSC2, thus inhibited proliferation, invasion and promoted apoptosis. Dual luciferase assay demonstrated that TUSC2P 3'UTR decoyed miR-17-5p, miR-520a-3p, miR-608, miR-661 from binding to TUSC2.
TUSC2P can suppresses the tumor function of esophageal squamous cell carcinoma by regulating TUSC2 expression and may also serve as a prognostic factor for ESCC patients.
假基因是与母蛋白编码基因具有高度同源性的 RNA 转录本。尽管假基因丧失了产生蛋白质的能力,但它仍然发挥着重要的生物学功能,并在多种肿瘤的发病机制中发挥着重要作用;然而,假基因在食管鳞状细胞癌(ESCC)中的作用还不清楚。
通过体外和体内实验细胞增殖、侵袭和凋亡实验来研究 TUSC2P 在 ESCC 中的作用,以评估 TUSC2P 对 ESCC 肿瘤生物学的影响。通过定量实时 PCR(qRT-PCR)和 Western blot 在 EC109 和 TE-1 细胞以及 ESCC 患者中评估相对基因的表达。3'UTR 荧光素酶测定用于证实 miRNA 与 TUSC2 和 TUSC2P 3'UTR 的直接结合。通过生存分析(n=56)预测 TUSC2P、TUSC2 与 ESCC 预后的关系。
与配对的正常相邻组织相比,ESCC 组织中下调了假基因 TUSC2P,TUSC2P 的表达与 ESCC 患者的生存显著相关。在 EC109 和 TE-1 细胞中过表达 TUSC2P 导致 TUSC2 的表达发生改变,从而抑制增殖、侵袭并促进凋亡。双荧光素酶测定表明 TUSC2P 3'UTR 可使 miR-17-5p、miR-520a-3p、miR-608、miR-661 逃避与 TUSC2 的结合。
TUSC2P 通过调节 TUSC2 的表达可以抑制食管鳞状细胞癌的肿瘤功能,并且可能也作为 ESCC 患者的预后因素。