Methylation of RILP in lung cancer promotes tumor cell proliferation and invasion.

Abstract

Rab-interacting lysosomal protein (RILP) has been suggested to perform as a tumor suppressor in breast and prostate cancer cell lines. However, its expression profile and functional role in lung cancer have never been investigated. We applied the well-established cancer genomic database-The Cancer Genome Atlas to compare the RILP expression and methylation between lung cancer tissues and normal tissues. The potential correlation of RILP with clinical characteristics of lung cancer patients (e.g., stages, smoking, TP53, and methylation) was also be explored. Our results showed that the downregulation of RILP and upregulation of RILP methylation were identified in lung cancer tissues compared to normal healthy tissues. Downregulation of RILP was positively associated with lung cancer later stage (N3), smoking history, TP53 mutation, and poor prognosis, as well as inversely correlated with DNA (cytosine-5)-methyltransferase 1 (DNMT1) expression. Demethylation treatment enhanced RILP expression in lung cancer cells, suggesting hypermethylation is responsible for RILP silencing in lung cancer. We further found that RILP depletion promoted lung cancer cell proliferation, migration, and invasion.We concluded that RILP acts as a tumor suppressor in lung cancer cells. Our results provided the theoretical basis for developing RILP-targeting or demethylating agents for lung cancer treatment.