DLGAP5 Drives Lung Adenocarcinoma Cell Growth by Promoting Autophagy Activity

Autophagy is reported to participate in tumorigenesis and plays a vital role in tumor cell survival. Here, we aimed to elucidate the regulatory mechanism between discs large homolog-associated protein 5 (DLGAP5) and autophagy in lung adenocarcinoma (LUAD) development.

RT-qPCR and western blot methods were utilized to assess DLGAP5 expression. Cell proliferation and apoptosis abilities were monitored utilizing Cell Counting Kit 8 (CCK-8), EdU, and flow cytometry assays. Autophagy-related proteins were quantified using western blot and immunofluorescence analysis. A xenograft tumor model was established to measure tumor growth.

DLGAP5 was significantly overexpressed in LUAD cell lines compared to 16HBE cells, especially in PC-9 and A549 cells. Functional assays highlighted that loss of function of DLGAP5 repressed cell proliferation and triggered apoptosis both in vitro and in vivo, while DLGAP5 overexpression had the opposite effect. After DLGAP5 blockage, the autophagy-related LC3II/I and Beclin1 expressions declined, while p62 expression increased. Moreover, the increased proliferation and autophagy activity and suppressed apoptosis mediated by DLGAP5 overexpression were greatly restrained after 3-MA (an autophagy-specific inhibitor).

To sum up, DLGAP5 could contribute to proliferation and impede apoptosis of LUAD cells by activating autophagy activity, suggesting that targeting DLGAP5 might be a promising approach for LUAD treatment.