The lncRNA MEG3/miR-16-5p/VGLL4 regulatory axis is involved in etoposide-induced senescence of tumor cells.

OBJECTIVE The senescence of tumor cells is an important tumor suppressor mechanism. The present study aimed to investigate the role of long noncoding RNA (lncRNA) MEG3 in the senescence process of tumor cells and its potential molecular mechanism by competitively binding with microRNA miR-16-5p to regulate the expression of VGLL4 (encoding vestigial like family member 4). METHODS We used etoposide to construct senescence models of tumor cells. The degree of cellular senescence was detected by senescence associated β-galactosidase, cell cycle and senescence-associated secretory phenotype. The expression of lncRNA MEG3, miR-16-5p, and VGLL4 in senescent or non-senescent cells was evaluated using quantitative real-time reverse transcription PCR (qRT-PCR) or western blotting. Dual luciferase reporter assays were used to detect the binding of miR-16-5p to lncRNA MEG3 and VGLL4. The mRNA and protein expression levels of senescence-related markers (p53, p21, and p16) were detected using qRT-PCR or western blotting. RESULTS Compared with that in control group, the expression of lncRNA MEG3 and VGLL4 were significantly upregulated in senescent cells. Knockdown of lncRNA MEG3 and VGLL4 reduced the degree of senescence and the expression of p21 and p16. LncRNA MEG3 interfered with expression of miR-16-5p in senescent A549 and MCF-7 cells. The expression of VGLL4 was regulated by miR-16-5p in senescent A549 and MCF-7 cells. LncRNA MEG3 participated in the senescent progress of tumor cells induced by etoposide via the miR-16-5p/VGLL4 axis. CONCLUSIONS Our study confirmed the regulatory role of the lncRNA MEG3/miR-16-5p/VGLL4 axis in the low-dose etoposide-induced tumor cell senescence model, which has potential clinical application value to treat malignant tumors.