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MLK 3 silence induces cervical cancer cell apoptosis via the Notch‐1/autophagy network
Author(s) -
Ma Liya,
Cheng Yongchong,
Zeng Jingjie
Publication year - 2019
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.13123
Subject(s) - autophagy , gene knockdown , cancer research , hela , apoptosis , carcinogenesis , protein kinase a , microbiology and biotechnology , cancer cell , cell , chemistry , biology , cell growth , kinase , cancer , biochemistry , genetics
Mixed‐lineage kinase 3 ( MLK 3), the mitogen‐activated protein kinase kinase kinase ( MAP 3K), has been recognized as a player in tumorigenesis and oncogenic signalling, yet its detailed functions and signalling in cervical cancer have not been fully elucidated. Here, we identify that cervical cancer cells display higher mRNA and protein levels of MLK 3 than normal cervical epithelial squamous cells. In HeLa and SiHa cell, MLK 3 knockdown using si RNA remarkably suppressed cell survival and promoted cell apoptosis, with increased expression of the apoptosis‐related protein Bax and reduced Bcl‐2. Moreover, MLK 3 knockdown promoted cell autophagy, demonstrated by increased ratio of autophagy‐related proteins LC 3 II / LC 3I and decreased p62 expression in MLK 3 depletion cells. Furthermore, MLK 3 knockdown remarkably abolished Notch‐1 expression in cervical cancer cells. By co‐treating Hela cells with MLK 3 specific si RNA and pc DNA 3.1‐Notch‐1 overexpression plasmid or autophagy inhibitor 3‐ MA , we found that MLK 3 played its role in cervical cancer cells via the Notch‐1/autophagy network. Our results demonstrate the importance of MLK 3 in cervical cancer progression via modulating the Notch‐1/autophagy network, and suggest that MLK 3 is a promising therapeutic target for cervical cancer.