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

Ye Tao, Peipei Yue, Yongnan Miao, Shuting Gao, Biao Wang, Sean X. Leng, Xin Meng, Haiyan Zhang

Research output: Contribution to journalArticlepeer-review

Abstract

Background: The senescence of tumor cells is an important tumor suppressor mechanism. The present study aimed to investigate the role of long non-coding RNA (lncRNA) MEG3 (maternally expressed gene 3) 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 a quantitative real-time reverse transcriptase-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 to the control group, the expression of lncRNA MEG3 and VGLL4 was significantly up-regulated 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 the 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: The present study has 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 with respect to treating malignant tumors.

Original languageEnglish (US)
Article numbere3291
JournalJournal of Gene Medicine
Volume23
Issue number2
DOIs
StatePublished - Feb 2021

Keywords

  • breast cancer
  • cell senescence
  • etoposide
  • lncRNA MEG3
  • lung adenocarcinoma

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Drug Discovery
  • Genetics(clinical)

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