Background: As a highly malignant tumor, cholangiocarcinoma poses a serious threat to human life and health, so exploring the mechanisms of its development and progression at a molecular level is of great significance to the diagnosis and treatment of the disease.
Objective: This study was aimed at investigating the effects and related mechanisms of LncRNA TUG1 on cholangiocarcinoma cells.
Methods: Cholangiocarcinoma tissues and adjacent tissues (n=82 each), human cholangiocarcinoma cell lines (RBE, QBC939, HuH28), and a human normal biliary epithelial cell line (HIBE) were collected. miR-29a-mimics, miR-29a-inhibitor, miR-NC, si-TUG1, pcDNA3.1 TUG1, and NC were transfected into the cholangiocarcinoma cells. qRT-PCR was performed to detect TUG1 and miR-29a expression in the cholangiocarcinoma tissues and cells. Western blotting (WB) was conducted to detect the expression of Bax, Caspase-3, and Bcl-2 in the cells. CCK-8 assay, Transwell, and flow cytometry were carried out to detect cell proliferation, invasion, and apoptosis. Dual luciferase reporter gene assay (DLRGA) was performed to confirm the correlation of TUG1 with miR-29a.
Results: TUG1 was highly expressed while miR-29a was poorly expressed in cholangiocarcinoma cells. TUG1 expression was negatively correlated with miR-29a expression, and TUG1 had a relatively high diagnostic value for cholangiocarcinoma. Cell experiments showed that inhibiting TUG1 expression or up-regulating miR-29a expression could inhibit cholangiocarcinoma cells from proliferation and invasion, and promote their apoptosis, while up-regulating TUG1 or inhibiting miR-29a could promote the proliferation and invasion but inhibit the apoptosis. Rescue experiment showed that overexpressing miR-29a could reverse the effects of high TUG1 expression on cholangiocarcinoma cells. DLRGA confirmed that there was a regulatory relationship between TUG1 and miR-29a.
Conclusion: TUG1 is highly expressed in cholangiocarcinoma tissues. It can promote the growth and metastasis of cholangiocarcinoma cells by inhibiting miR-29a, so it may be a new target for diagnosing and treating cholangiocarcinoma.
Keywords: LncRNA TUG1, miR-29a, cholangiocarcinoma, proliferation, invasion, apoptosis