Long non-coding RNA TMPO-AS1 promotes cell proliferation, migration, invasion and epithelial-to-mesenchymal transition in gallbladder carcinoma by regulating the microRNA-1179/E2F2 axis

长链非编码RNA TMPO-AS1通过调控microRNA-1179/E2F2轴促进胆囊癌细胞增殖、迁移、侵袭及上皮间质转化

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作者:Zhenghui Sui, Xin Sui

Abstract

Gallbladder carcinoma (GBC), which is a common tumor of the biliary system, poses a serious threat to human life and health. The present study aimed to investigate the molecular mechanism of the long non-coding (lnc)RNA thymopoietin antisense transcript 1 (TMPO-AS1)/microRNA (miRNA/miR)-1179/E2F transcription factor 2 (E2F2) axis in GBC. The viability, proliferation, migration, invasion and epithelial-to-mesenchymal transition (EMT) of GBC cell lines were assessed via the Cell Counting Kit-8, colony formation, Transwell migration and invasion, immunofluorescence and western blot assays. In the present study, lncRNA TMPO-AS1 was significantly upregulated in clinical GBC tissues and cell lines, and was highly expressed in stage III+IV patients with GBC compared with stage I+II patients with GBC. In addition, the overall survival rate of patients with low TMPO-AS1 expression levels was higher than those with high TMPO-AS1 expression levels. Furthermore, TMPO-AS1 knockdown inhibited the viability, proliferation, migration, invasion and EMT of GBC cell lines. In addition, miR-1179 expression was downregulated in clinical GBC tissues and cell lines, and negatively correlated with TMPO-AS1 expression. The results revealed that miR-1179 is a target of TMPO-AS1, which was confirmed via the dual-luciferase reporter assay and RNA pull-down analysis. Overexpression of miR-1179 inhibited the viability, proliferation, migration, invasion and EMT of GBC cell lines. Furthermore, E2F2 was verified as a direct target of miR-1179 by binding to its 3'-untranslated region. E2F2 expression was significantly upregulated in clinical GBC tissues and cell lines, and negatively correlated with miR-1179 expression. Notably, E2F2 knockdown partially hindered the effects of TMPO-AS1/miR-1179 on the proliferation and metastasis of GBC cell lines. Taken together, the results of the present study suggest that TMPO-AS1 potentially plays a tumor-promoting role in the occurrence and development of GBC, which may be achieved by regulating the miR-1179/E2F2 axis.

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