Abnormal methylation mediated upregulation of LINC00857 boosts malignant progression of lung adenocarcinoma by modulating the miR-486-5p/NEK2 axis

LINC00857 is frequently dysregulated in varying cancers, which in turn exerts carcinogenic effects; however, its DNA methylation status in promoter region and molecular mechanisms underlying the progression of lung adenocarcinoma (LUAD) remain rarely understood. Through bioinformatics analysis, we examined the expression state and methylation site of LINC00857 in LUAD and further investigated the properties of LINC00857 as a competitive endogenous RNA in the cancer progression. The current study revealed that the overexpression of LINC00857 in LUAD tissue and cells was mainly caused by the hypomethylation of the promoter region. LINC00857 knockdown prominently reduced cell proliferation, impeded cell migration and invasion, and restrained lymph node metastasis, with enhancing radiosensitivity. The effects of LINC00857 on tumor growth were also investigated in nude mice models. Subsequently, the downstream factors, miR-486-5p and NEK2, were screened, and the putative regulatory axis was examined. Overall, the regulatory effect of methylation-mediated LINC00857 overexpression on miR-486-5p/NEK2 axis may be a new mechanism for LUAD progression. Low methylation of LINC00857 in the promoter region led to its high expression. Knockdown of LINC00857 restrained lymph node metastasis and stimulated radiosensitivity of LUAD cells. LINC00857 acted as a ceRNA, regulating NEK2 expression by binding to miR-486-5p. image