TCN1 knockdown inhibits the progression and glycolysis of non-small cell lung cancer via regulating B3GNT3.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality globally. Transcobalamin 1 (TCN1) is a driver associated with the progression of various cancers. However, the role of TCN1 in NSCLC remains elusive. The current research aimed to disclose the biological function and regulatory mechanisms of TCN1 in NSCLC. The expression pattern of TCN1 in NSCLC was first identified via qRT-PCR and western blotting. Functional assays including CCK-8, Transwell, Epithelial-mesenchymal transition (EMT), and glycolysis detection were performed to evaluate the effects of TCN1 on the malignant phenotype of NSCLC cells. Then LinkedOmics database and KEGG pathway analysis were employed to explore TCN1-mediated molecular pathways. Finally, the rescue tests were conducted to validated the underlying molecular mechanisms. Here, we observed that TCN1 was apparently overexpressed in NSCLC and predicted poor prognosis. TCN1 knockdown restrained the proliferation, metastasis, EMT, and glycolysis of NSCLC cells. Mechanism studies demonstrated that TCN1 positively regulated B3GNT3 level via activating the EGFR pathway. Knockdown of B3GNT3 also suppressed the malignant progression and glycolysis of NSCLC cells, and its overexpression partially rescued the effects of TCN1 knockdown. In vivo experiments presented that TCN1 knockdown attenuated tumor growth in the xenograft mouse model and downregulated B3GNT3 expression. Collectively, TCN1 overexpression aggravated NSCLC progression by regulating the expression of B3GNT3. The TCN1-B3GNT3 axis served a key part in the growth, migration, invasion, and glycolysis of NSCLC cells, making it a potential therapeutic target for NSCLC treatment.