TUG1 as ceRNA combined with miR-29a to promotes the expression of IFITM3 in hepatocellular carcinoma

Abstract

Background: Numerous studies have shown that TUG1 has an important relationship with tumorigenesis. TUG1 is highly expressed in most tumors and can promote tumor development. However, the role of TUG1 in hepatocellular carcinoma (HCC) remains to be studied. miR-29a plays a tumor suppressor role in a variety of tumors, and there is a relationship between TUG1 and miR-29a, but the specific relationship and mechanism of action are still unclear. miR-29a can inhibit the expression of IFITM3. However, the regulatory relationship between these three components requires elucidation. This study aimed to investigate the regulatory relationship between TUG1, miR-29a, and IFITM3 in human hepatocarcinogenesis.Methods: The expression levels of TUG1 and miR-29a in tumor tissues and adjacent non-tumor tissues of 41 HCC patients were detected by real-time quantitative polymerase chain reaction. The migration and invasion of liver cancer cells were studied by a wound healing assay and the Transwell method. The apoptosis rate of hepatocarcinoma cells was detected by flow cytometry, and the proliferation rate of hepatoma cells was detected by the EdU method. Immunofluorescence was selected to detect the expression of TUG1 and IFITM3 in HCC-LM3 and HL-7702. The relationship between TUG1 and miR-29a was detected using a double luciferase report and FISH. Tumors were established in vivo by subcutaneous injection of hepatocellular carcinoma cells into nude mice and injection of these cells into the tail vein. Western blotting was used to quantify the biomarkers. Results: TUG1 expression increased significantly in both tumor tissues and HCC cells. The expression of miR-29a in liver cancer tissues was also significantly lower than that in normal human liver tissues. The expression of TUG1 in HCC tissue samples was negatively correlated with that of miR-29a. Moreover, the expression of TUG1 was positively correlated with the expression of IFITM3. TUG1 can regulate the migration, invasion, apoptosis, and proliferation of HCC lines in vitro and regulate the development of tumors in vivo. Knocking down TUG1 will increase miR-29a expression, and thus, weaken the invasion, migration, and proliferation of HCC cells and enhance their apoptosis. miR-29a can affect the occurrence and progression of liver cancer through IFITM3. It was found that TUG1 regulates IFITM3 in HCC cells via miR-29a, and its expression affects cell invasion, migration, proliferation, and apoptosis.Conclusion: As a CeRNA, TUG1 competitively binds mir-29a to regulate IFITM3 and promote the development of liver cancer. Downregulation of TUG1 can significantly inhibit the migration, invasion, and proliferation of liver cancer cells, and TUG1 is expected to serve as a key gene to improve the prognosis of patients.

New Insights into the Role of miR-29a in Hepatocellular Carcinoma: Implications in Mechanisms and Theragnostics

“…Zhu et al showed that lncRNA HULC promotes HCC cells proliferation by functioning to sponge and downregulate miR-29 [ 60 ]. A preprint report conducted by Liu et al showed that lncRNA TUG1 competitively targets miR-29a to upregulate the expression of a oncogenic factor, interferon-induced transmembrane protein 3 (IFITM3), resulting in increased proliferation, invasion, and migration of HCC [ 61 ]. In addition, Qu et al identified that lncRNA HOXA-AS3 acts as a tumor-promoting factor in gastric cancer cells by suppressing miR-29a, leading to the activation of lymphotoxin β receptor (LTBR)/NF-κB signaling [ 62 ].…”