DSG2 and c-MYC Interact to Regulate the Expression of ADAM17 and Promote the Development of Cervical Cancer

Li-Mian Song; Du-Juan Yao; Lin Xia; Xu-Ming Wang; Tian Liu; Qian-Qian Tang; Jun Zhou

doi:10.2147/CMAR.S456548

DSG2 and c-MYC Interact to Regulate the Expression of ADAM17 and Promote the Development of Cervical Cancer

Cancer Manag Res. 2024 Jun 25:16:703-710. doi: 10.2147/CMAR.S456548. eCollection 2024.

Authors

Li-Mian Song^#¹, Du-Juan Yao^#¹, Lin Xia¹, Xu-Ming Wang², Tian Liu², Qian-Qian Tang¹, Jun Zhou¹

Affiliations

¹ Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
² Department of Pathology, Affiliated Hospital of Guilin Medical College, Guilin, People's Republic of China.

^# Contributed equally.

Abstract

Purpose: To explore the effect of DSG2 on the growth of cervical cancer cells and its possible regulatory mechanism.

Methods: The expression levels and survival prognosis of DSG2 and ADAM17 in cervical squamous cell carcinoma tissues and adjacent normal tissues were analyzed by bioinformatics. CCK-8 assay, colony formation assay and Transwell assay were used to detect the effects of DSG2 on the proliferative activity, colony formation ability and migration ability of SiHa and Hela cells. The effect of DSG 2 on the level of ADAM17 transcription and translation was detected by qPCR and Western blot experiments. The interaction between DSG2 and c-MYC was detected by immunocoprecipitation. c-MYC inhibitors were used in HeLa cells overexpressing DSG2 to analyze the effects of DSG2 and c-MYC on proliferation, colony formation and migration of Hela cells, as well as the regulation of ADAM17 expression.

Results: DSG2 was highly expressed in cervical squamous cell carcinoma compared with normal tissues (P<0.05), and high DSG2 expression suggested poor overall survival (P<0.05). After DSG2 knockdown, the proliferative activity, colony formation and migration ability of SiHa and Hela cells were significantly decreased (P<0.05). Compared with adjacent normal tissues, ADAM17 was highly expressed in cervical squamous cell carcinoma (P<0.05), and high ADAM17 expression suggested poor overall survival in cervical cancer patients (P<0.05). The results of immunocoprecipitation showed the interaction between DSG2 and c-MYC. Compared with DSG2 overexpression group, DSG2 overexpression combined with c-MYC inhibition group significantly decreased cell proliferation, migration and ADAM17 expression (P < 0.05).

Conclusion: DSG2 is highly expressed in cervical cancer, and inhibition of DSG2 expression can reduce the proliferation and migration ability of cervical cancer cells, which may be related to the regulation of ADAM17 expression through c-MYC interaction.

Keywords: ADAM17; DSG2; c-MYC; cervical cancer; migration; proliferation.

Grants and funding

This work is supported by Young and Middle aged Staff Research Ability Enhancement Project of Guilin Medical College (2018g1mcy037).