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

IF 2.5 4区 医学 Q3 ONCOLOGY Cancer Management and Research Pub Date : 2024-06-25 eCollection Date: 2024-01-01 DOI:10.2147/CMAR.S456548
Li-Mian Song, Du-Juan Yao, Lin Xia, Xu-Ming Wang, Tian Liu, Qian-Qian Tang, Jun Zhou
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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.

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DSG2 和 c-MYC 相互作用,调控 ADAM17 的表达并促进宫颈癌的发展
目的:探讨DSG2对宫颈癌细胞生长的影响及其可能的调控机制:方法:采用生物信息学方法分析DSG2和ADAM17在宫颈鳞癌组织和邻近正常组织中的表达水平和生存预后。采用CCK-8试验、集落形成试验和Transwell试验检测DSG2对SiHa和Hela细胞增殖活性、集落形成能力和迁移能力的影响。通过 qPCR 和 Western 印迹实验检测了 DSG2 对 ADAM17 转录和翻译水平的影响。在过表达DSG2的Hela细胞中使用c-MYC抑制剂,分析DSG2和c-MYC对Hela细胞增殖、集落形成和迁移的影响,以及对ADAM17表达的调控:结果发现:与正常组织相比,DSG2在宫颈鳞状细胞癌中高表达:DSG2在宫颈癌中高表达,抑制DSG2的表达可降低宫颈癌细胞的增殖和迁移能力,这可能与通过c-MYC相互作用调控ADAM17的表达有关。
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来源期刊
Cancer Management and Research
Cancer Management and Research Medicine-Oncology
CiteScore
7.40
自引率
0.00%
发文量
448
审稿时长
16 weeks
期刊介绍: Cancer Management and Research is an international, peer reviewed, open access journal focusing on cancer research and the optimal use of preventative and integrated treatment interventions to achieve improved outcomes, enhanced survival, and quality of life for cancer patients. Specific topics covered in the journal include: ◦Epidemiology, detection and screening ◦Cellular research and biomarkers ◦Identification of biotargets and agents with novel mechanisms of action ◦Optimal clinical use of existing anticancer agents, including combination therapies ◦Radiation and surgery ◦Palliative care ◦Patient adherence, quality of life, satisfaction The journal welcomes submitted papers covering original research, basic science, clinical & epidemiological studies, reviews & evaluations, guidelines, expert opinion and commentary, and case series that shed novel insights on a disease or disease subtype.
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