ALG3 contributes to the malignancy of non-small cell lung cancer and is negatively regulated by MiR-98-5p

Objective: Alpha-1,3-mannosyltransferase (ALG3) is an oncoprotein associated with multiple malignancies. We aimed to investigate the role and potential mechanisms of ALG3 in non-small cell lung cancer (NSCLC). Methods: We detected the expressions of ALG3 in NSCLC tissues and adjacent tissues by RT-PCR, western blot and immunohistochemistry, respectively. Chi-square test was used to analyze the correlation between ALG3 expression and pathological paremeters. Then we used shRNA to construct a low expression model of ALG3 in NCI-H292 and NCI-H460. CCK-8 assay and transwell assay were then performed to monitor the proliferation, migration and invasion of NSCLC cells. Western blot was to detect the expression of EMT-related indicators. Further, the interaction of miR-98-5p with ALG3 was verified by luciferase reporter assay. Results: The expression of ALG3 in NSCLC tissues was higher than that in normal tissues, and the increase in ALG3 expression was significantly associated with higher T stage, lymph node metastasis, and poor tissue differentiation. Patients with high ALG3 expression had a worse prognosis. ALG3 knockdown inhibited the proliferation, migration and invasion of NSCLC cells. In addition, the knockdown of ALG3 resulted in increased expression of EMT-related protein E-cadherin, while N-cadherin and Vimentin expression was decreased. Dual luciferase assay confirmed that miR-98-5p can specifically bind to the 3'UTR of ALG3 and reduces its expression and activity. Conclusion: ALG3 can promote the progression of NSCLC and is negatively regulated by miR-98-5p.