Cx32 promotes autophagy and produces resistance to SN‑induced apoptosis via activation of AMPK signalling in cervical cancer

Fan,Li-Xia; Tao,Liang; Lai,Yong-Chang; Cai,Shao-Yi; Zhao,Zi-Yu; Yang,Feng; Su,Ri-Ya; Wang,Qin

doi:10.3892/ijo.2021.5300

Cx32 promotes autophagy and produces resistance to SN‑induced apoptosis via activation of AMPK signalling in cervical cancer

Authors:
- Li-Xia Fan
- Liang Tao
- Yong-Chang Lai
- Shao-Yi Cai
- Zi-Yu Zhao
- Feng Yang
- Ri-Ya Su
- Qin Wang
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Affiliations: Department of Pharmacology, Zhongshan School of Medicine, Sun Yat‑Sen University, Guangzhou, Guangdong 510080, P.R. China, Department of Urology, The Eighth Affiliated Hospital, Sun Yat‑Sen University, Shenzhen, Guangdong 518033, P.R. China
Published online on: December 30, 2021 https://doi.org/10.3892/ijo.2021.5300
Article Number: 10

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Abstract

The roles of gap junctions (GJs) and its components, connexins, in the autophagy of cervical cancer cells have been rarely investigated. Our previous study demonstrated that connexin 32 (Cx32) exerted an anti‑apoptotic effect on cervical cancer. However, as an important regulator of apoptosis, whether the autophagy is involved in the function of Cx32 on cervical cancer cells is not well defined. The present study aimed to investigate the role of Cx32 on autophagy and apoptosis inhibition in cervical cancer cells. The expression levels of Cx32 and the autophagy‑associated protein LC3‑Ⅱ in paracancerous cervical tissues (n=30) and cervical cancer (n=50) tissues were determined via western blotting. In total, 45 cervical cancer specimens were used to evaluate the clinical relevance of Cx32 and LC3‑Ⅱ. It was found that both Cx32 and LC3‑Ⅱ were upregulated in cervical cancer tissues compared with those in paracancerous cervical tissues. The effect of Cx32 on autophagy was examined by detecting the change of LC3‑Ⅱ using western blotting, transfection with enhanced green fluorescent protein‑LC3 plasmid and transmission electron microscopy analysis. Overexpression of Cx32 significantly enhanced autophagy in HeLa‑Cx32 cells, whereas knockdown of Cx32 suppressed autophagy in C‑33A cells. The flow cytometry results demonstrated that Cx32 inhibited the apoptosis of cervical cancer cells by promoting autophagy. Moreover, Cx32 triggered autophagy via the activation of the AMP‑activated protein kinase (AMPK) signalling, regardless of the presence or absence of GJs. Collectively, it was identified that Cx32 exerted its anti‑apoptotic effect by activating autophagy via the AMPK pathway in cervical cancer, which demonstrates a novel mechanism for Cx32 in human cervical cancer progression.

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