Long non-coding RNA TPTEP1 exerts inhibitory effects on hepatocellular carcinoma by impairing microRNA-454-3p-mediated DLG5 downregulation

• Published in: Digestive and liver disease 2022-02, Vol.54 (2), p.268-279
• Main Authors: Dong, Yuandi, Wang, Qingshan, Sun, Jianmin, Liu, Haishi, Wang, Haiyang
• Format: Article
• Language: English
• Subjects: Akt signaling pathway; Animals; Biomarkers, Tumor - genetics; Carcinogenesis - genetics; Carcinoma, Hepatocellular - genetics; Cell Movement - genetics; Cell Proliferation - genetics; Disease Models, Animal; Dlg5; Down-Regulation - genetics; Hepatocellular carcinoma; Humans; Liver Neoplasms - genetics; Long non-coding rna tptep1; Membrane Proteins - genetics; Mice; Microrna-454–3p; MicroRNAs - genetics; Neoplasm Invasiveness - genetics; Proto-Oncogene Proteins c-akt - metabolism; Pseudogenes - genetics; PTEN Phosphohydrolase - genetics; RNA, Long Noncoding - genetics; Signal Transduction - genetics; Tumor Suppressor Proteins - genetics; Up-Regulation - genetics
• ISSN: 1590-8658; 1878-3562
• DOI: 10.1016/j.dld.2021.04.014

Hepatocellular carcinoma (HCC) is usually diagnosed at late stages, making it the second cause of malignancy-related death across the world. Long noncoding RNAs (lncRNAs) are of significance to tumorigenesis, highly suggestive of their functional roles as novel biomarkers for cancer therapy. The current study investigated the specific role of lncRNA TPTE pseudogene 1 (TPTEP1) in HCC. Expression of lncRNA TPTEP1, microRNA-454-3p (miR-454-3p) and discs large homolog 5 (DLG5) was determined in tissues samples from the recruited patients with HCC. Cell proliferation, migration and invasion assays were performed to determine effects of lncRNA TPTEP1, miR-454-3p and DLG5 on the malignant phenotype of tumor cells. Finally, the mouse HCC model was also established to disclose the tumor suppressor effects of lncRNA TPTEP1 in vivo. LncRNA TPTEP1 was downregulated both in HCC cells and tissues, and played a negative regulatory role in HCC cell proliferation, migration and invasion. Mechanistically, lncRNA TPTEP1 competitively bound to miR-454-3p, thereby upregulating its endogenous target DLG5. Moreover, lncRNA TPTEP1 hindered activation of the protein kinase B signaling pathway, causing inhibited malignant phenotypes of HCC cells. Also, lncRNA TPTEP1 suppressed tumor growth and extrahepatic metastasis (lung) via miR-454-3p/DLG5 axis. Taken together, this research revealed a concrete mechanism of lncRNA TPTEP1 in HCC.