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The lncRNA MEG3/miR‐16‐5p/VGLL4 regulatory axis is involved in etoposide‐induced senescence of tumor cells
Author(s) -
Tao Ye,
Yue Peipei,
Miao Yongnan,
Gao Shuting,
Wang Biao,
Leng Sean X.,
Meng Xin,
Zhang Haiyan
Publication year - 2021
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.3291
Subject(s) - senescence , meg3 , gene knockdown , microrna , biology , ectopic expression , cancer research , microbiology and biotechnology , cell culture , long non coding rna , rna , gene , genetics
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.