Long Noncoding RNA TOB1-AS1 Represses Cervical Cancer Cell Proliferation, Invasion, and Migration via the MicroRNA-27a-3p/Thioredoxin-Interacting Protein Molecular Axis.

IF 3.1
Yang Wang, You-Xiang Hou, Li Xie, Yi-La Xia, Yi-Na Wang
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Abstract

Cervical cancer (CC) remains a major global health concern, particularly due to its aggressive nature and limited treatment options in advanced stages. Long noncoding RNA (lncRNA) TOB1-AS1 has been proposed as a tumor suppressor, yet its regulatory mechanism in CC remains unclear. This study aimed to elucidate the role of TOB1-AS1 in CC progression through the miR-27a-3p/thioredoxin-interacting protein (TXNIP) molecular axis. Functional gain- and loss-of-function assays were conducted to assess the effects of TOB1-AS1, miR-27a-3p, and TXNIP on cell proliferation, invasion, migration, and apoptosis. RT-qPCR, Western blotting, dual-luciferase reporter assays, and in vivo xenograft models were used to validate interactions and phenotypic outcomes. TOB1-AS1 was found to be downregulated in CC cells. Its overexpression suppressed proliferation, invasion, and migration, while enhancing apoptosis. Mechanistically, TOB1-AS1 functioned as a competing endogenous RNA (ceRNA) by sponging miR-27a-3p, thereby restoring TXNIP expression. Modulating miR-27a-3p or TXNIP levels partially reversed the effects of TOB1-AS1. In vivo, TOB1-AS1 overexpression significantly inhibited tumor growth and altered miR-27a-3p and TXNIP expression profiles. These findings suggest that lncRNA TOB1-AS1 acted as a ceRNA of miR-27a-3p to upregulate TXNIP, thereby suppressing CC cell proliferation, invasion and migration.

长链非编码RNA to1 - as1通过MicroRNA-27a-3p/硫氧还蛋白相互作用蛋白分子轴抑制宫颈癌细胞增殖、侵袭和迁移。
子宫颈癌(CC)仍然是一个主要的全球健康问题,特别是由于其侵袭性和晚期治疗选择有限。长链非编码RNA (lncRNA) TOB1-AS1被认为是一种肿瘤抑制因子,但其在CC中的调控机制尚不清楚。本研究旨在通过miR-27a-3p/硫氧还蛋白相互作用蛋白(TXNIP)分子轴阐明to1 - as1在CC进展中的作用。通过功能增益和功能丧失测定来评估TOB1-AS1、miR-27a-3p和TXNIP对细胞增殖、侵袭、迁移和凋亡的影响。采用RT-qPCR、Western blotting、双荧光素酶报告基因检测和体内异种移植物模型来验证相互作用和表型结果。在CC细胞中发现to1 - as1表达下调。其过表达抑制细胞增殖、侵袭和迁移,同时促进细胞凋亡。在机制上,TOB1-AS1通过海绵化miR-27a-3p作为竞争内源性RNA (ceRNA)发挥作用,从而恢复TXNIP的表达。调节miR-27a-3p或TXNIP水平部分逆转了TOB1-AS1的作用。在体内,TOB1-AS1过表达显著抑制肿瘤生长,改变miR-27a-3p和TXNIP的表达谱。这些发现表明,lncRNA to1 - as1作为miR-27a-3p的ceRNA上调TXNIP,从而抑制CC细胞的增殖、侵袭和迁移。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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