Sui Zhenghui, Sui Xin
Department of General Surgery, The People's Hospital of Danyang and Affiliated Danyang Hospital of Nantong University, Danyang, Jiangsu 212300, P.R. China.
Oncol Lett. 2021 Dec;22(6):855. doi: 10.3892/ol.2021.13116. Epub 2021 Oct 29.
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.
胆囊癌（GBC）是胆道系统的常见肿瘤，对人类生命健康构成严重威胁。本研究旨在探讨长链非编码（lnc）RNA胸腺生成素反义转录本1（TMPO-AS1）/微小RNA（miRNA/miR）-1179/E2F转录因子2（E2F2）轴在胆囊癌中的分子机制。通过细胞计数试剂盒-8、集落形成、Transwell迁移和侵袭、免疫荧光及蛋白质印迹分析评估胆囊癌细胞系的活力、增殖、迁移、侵袭及上皮-间质转化（EMT）。在本研究中，lncRNA TMPO-AS1在临床胆囊癌组织和细胞系中显著上调，与I+II期胆囊癌患者相比，在III+IV期胆囊癌患者中高表达。此外，TMPO-AS1表达水平低的患者总生存率高于TMPO-AS1表达水平高的患者。此外，TMPO-AS1敲低抑制了胆囊癌细胞系的活力、增殖、迁移、侵袭及EMT。此外，miR-1179在临床胆囊癌组织和细胞系中表达下调，且与TMPO-AS1表达呈负相关。结果显示，miR-1179是TMPO-AS1的靶标，这通过双荧光素酶报告基因检测和RNA下拉分析得以证实。miR-1179过表达抑制了胆囊癌细胞系的活力、增殖、迁移、侵袭及EMT。此外，通过与E2F2的3'-非翻译区结合，证实E2F2是miR-1179的直接靶标。E2F2在临床胆囊癌组织和细胞系中表达显著上调，且与miR-1179表达呈负相关。值得注意的是，E2F2敲低部分阻碍了TMPO-AS1/miR-1179对胆囊癌细胞系增殖和转移的影响。综上所述，本研究结果表明，TMPO-AS1可能在胆囊癌的发生发展中发挥促肿瘤作用，这可能是通过调节miR-1179/E2F2轴实现的。
