ABSTRACT
PURPOSE: The expression and regulatory mechanism of NSUN6 in lung cancer are still unclear. Our study explored whether NSUN6 mediates progression of lung cancer by affecting NM23-H1 expression in an m5C-dependent manner. METHODS: qRT-PCR, CCK-8, colony formation, transwell, and Western blot analysis were employed to probe the impact of NSUN6 on lung cancer cell proliferation, migration, and epithelial-mesenchymal transition (EMT). RMVar database was utilized to forecast the downstream genes of NSUN6. The mode of interaction between NSUN6 and NM23-H1 was determined by dot blot, luciferase assay, m5C RIP, and cell function assays. The effect of NSUN6 expression on tumor growth was verified in vivo. RESULTS: Expression of NSUN6 was reduced in lung cancer cells, and over-expression of NSUN6 restricted the proliferation of lung cancer cells, migration, and EMT. NSUN6 regulated NM23-H1 expression by modifying the 3'-UTR of NM23-H1 mRNA through m5C and inhibited lung cancer cell proliferation, migration, and EMT. In vivo experiments also showed that over-expression of NSUN6 inhibited the occurrence of lung cancer. CONCLUSION: NSUN6 regulates NM23-H1 expression in an m5C-dependent manner to affect EMT in lung cancer. Thus, NSUN6 may be considered as a potential therapeutic target for lung cancer.
Subject(s)
Epithelial-Mesenchymal Transition , Lung Neoplasms , tRNA Methyltransferases , Humans , Cell Line, Tumor , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , tRNA Methyltransferases/metabolism , NM23 Nucleoside Diphosphate Kinases/metabolismABSTRACT
BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the deadliest malignancies. There is a growing body of evidence showing that long non-coding RNAs (lncRNAs) play critical roles in ESCC oncogenesis. The present study aimed to explore the role of LOC101928477, a newly discovered lncRNA, in the development and metastasis of ESCC. METHODS: In this study, real-time PCR, western blotting, cell counting kit-8 (CCK-8), flow cytometry, colony formation, wound healing, transwell migration/invasion assay, immunofluorescence, and immunohistochemistry were used. We also applied an in situ xenograft mouse model and a lung metastasis mouse model to verify our findings. RESULTS: We determined that LOC101928477 expression was inhibited in ESCC tissue and ESCC cell lines when compared with controls. Moreover, forced expression of LOC101928477 effectively inhibited ESCC cell proliferation, colony formation, migration, and invasion via suppression of epithelial-mesenchymal transition (EMT). Furthermore, LOC101928477 overexpression inhibited in situ tumor growth and lung metastasis in a mouse model. CONCLUSIONS: Together, our results suggested that LOC101928477 could be a novel suppressor gene involved in ESCC progression.
Subject(s)
Epithelial-Mesenchymal Transition/physiology , Esophageal Squamous Cell Carcinoma/genetics , RNA, Long Noncoding/metabolism , Adult , Aged , Animals , Disease Models, Animal , Disease Progression , Down-Regulation , Esophageal Squamous Cell Carcinoma/pathology , Humans , Male , Mice , Middle AgedABSTRACT
Lung adenocarcinoma is a major form of non-small-cell lung cancer that frequently strikes nonsmokers. The disease is often diagnosed at a late stage and the 5-year survival rate is very low. Although previous studies found many somatic alterations associated with lung adenocarcinoma, the molecular basis of the development and progression of the disease is not well understood. We found that long noncoding RNA (lncRNA) cancer susceptibility candidate 2 (CASC2), a putative tumor suppressor, was downregulated in both patient adenocarcinoma tissues and cultured lung cancer cells. Its tumor suppression function seemed to be dependent on its binding to miR-4735-5p. Changing the levels of CASC2 and miR-4735-3p in the cultured adenocarcinoma cells could affect the malignant phenotypes as well as growth of tumors derived from the cells injected into nude mice. Furthermore, the lncRNA and miR-4735-3p interplay likely the suppressed tumor growth through the downstream mammalian target of rapamycin signaling pathway. The results have revealed molecular details that may be critical for the development of lung adenocarcinoma, opening opportunities for the development of novel, and therapeutic tools.
