Pyroptosis-related gene GSDMC indicates poor prognosis and promotes tumor progression by activating the AKT/mTOR pathway in lung squamous cell carcinoma
Yi Zhang
Shengli Clinical Medical College, Fujian Medical University, Fuzhou, Fujian, China
Department of Clinical Laboratory, Fujian Provincial Hospital, Fuzhou, Fujian, China
Search for more papers by this authorYuzhi Wang
Department of Laboratory Medicine, Deyang People's Hospital, Deyang, Sichuan, China
Search for more papers by this authorJiamiao Weng
Shengli Clinical Medical College, Fujian Medical University, Fuzhou, Fujian, China
Department of Clinical Laboratory, Fujian Provincial Hospital, Fuzhou, Fujian, China
Search for more papers by this authorJianlin Chen
Shengli Clinical Medical College, Fujian Medical University, Fuzhou, Fujian, China
Department of Clinical Laboratory, Fujian Provincial Hospital, Fuzhou, Fujian, China
Search for more papers by this authorYue Zheng
Shengli Clinical Medical College, Fujian Medical University, Fuzhou, Fujian, China
Department of Clinical Laboratory, Fujian Provincial Hospital, Fuzhou, Fujian, China
Search for more papers by this authorYu Xia
Department of Clinical Laboratory, Fujian Provincial Hospital, Fuzhou, Fujian, China
Integrated Chinese and Western Medicine College, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China
Search for more papers by this authorZhixin Huang
Department of Clinical Laboratory, Fujian Provincial Hospital, Fuzhou, Fujian, China
Integrated Chinese and Western Medicine College, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China
Search for more papers by this authorLilan Zhao
Shengli Clinical Medical College, Fujian Medical University, Fuzhou, Fujian, China
Department of General Thoracic Surgery, Fujian Provincial Hospital, Fujian Medical University, Fuzhou, Fujian, China
Search for more papers by this authorXiongfeng Chen
Shengli Clinical Medical College, Fujian Medical University, Fuzhou, Fujian, China
Department of Scientific Research, Fujian Provincial Hospital, Fuzhou, Fujian, China
Search for more papers by this authorHaijun Tang
Shengli Clinical Medical College, Fujian Medical University, Fuzhou, Fujian, China
Fujian Provincial Key Laboratory of Critical Care Medicine, Fujian Provincial Key Laboratory of Cardiovascular Disease, Fuzhou, Fujian, China
Search for more papers by this authorCorresponding Author
Yi Huang
Shengli Clinical Medical College, Fujian Medical University, Fuzhou, Fujian, China
Department of Clinical Laboratory, Fujian Provincial Hospital, Fuzhou, Fujian, China
Fujian Provincial Key Laboratory of Critical Care Medicine, Fujian Provincial Key Laboratory of Cardiovascular Disease, Fuzhou, Fujian, China
Center for Experimental Research in Clinical Medicine, Fujian Provincial Hospital, Fuzhou, Fujian, China
Central Laboratory, Fujian Provincial Hospital, Fuzhou, Fujian, China
Correspondence Yi Huang, Shengli Clinical Medical College, Fujian Medical University, Fujian, Fuzhou 350001, China.
Email: [email protected]
Search for more papers by this authorYi Zhang
Shengli Clinical Medical College, Fujian Medical University, Fuzhou, Fujian, China
Department of Clinical Laboratory, Fujian Provincial Hospital, Fuzhou, Fujian, China
Search for more papers by this authorYuzhi Wang
Department of Laboratory Medicine, Deyang People's Hospital, Deyang, Sichuan, China
Search for more papers by this authorJiamiao Weng
Shengli Clinical Medical College, Fujian Medical University, Fuzhou, Fujian, China
Department of Clinical Laboratory, Fujian Provincial Hospital, Fuzhou, Fujian, China
Search for more papers by this authorJianlin Chen
Shengli Clinical Medical College, Fujian Medical University, Fuzhou, Fujian, China
Department of Clinical Laboratory, Fujian Provincial Hospital, Fuzhou, Fujian, China
Search for more papers by this authorYue Zheng
Shengli Clinical Medical College, Fujian Medical University, Fuzhou, Fujian, China
Department of Clinical Laboratory, Fujian Provincial Hospital, Fuzhou, Fujian, China
Search for more papers by this authorYu Xia
Department of Clinical Laboratory, Fujian Provincial Hospital, Fuzhou, Fujian, China
Integrated Chinese and Western Medicine College, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China
Search for more papers by this authorZhixin Huang
Department of Clinical Laboratory, Fujian Provincial Hospital, Fuzhou, Fujian, China
Integrated Chinese and Western Medicine College, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China
Search for more papers by this authorLilan Zhao
Shengli Clinical Medical College, Fujian Medical University, Fuzhou, Fujian, China
Department of General Thoracic Surgery, Fujian Provincial Hospital, Fujian Medical University, Fuzhou, Fujian, China
Search for more papers by this authorXiongfeng Chen
Shengli Clinical Medical College, Fujian Medical University, Fuzhou, Fujian, China
Department of Scientific Research, Fujian Provincial Hospital, Fuzhou, Fujian, China
Search for more papers by this authorHaijun Tang
Shengli Clinical Medical College, Fujian Medical University, Fuzhou, Fujian, China
Fujian Provincial Key Laboratory of Critical Care Medicine, Fujian Provincial Key Laboratory of Cardiovascular Disease, Fuzhou, Fujian, China
Search for more papers by this authorCorresponding Author
Yi Huang
Shengli Clinical Medical College, Fujian Medical University, Fuzhou, Fujian, China
Department of Clinical Laboratory, Fujian Provincial Hospital, Fuzhou, Fujian, China
Fujian Provincial Key Laboratory of Critical Care Medicine, Fujian Provincial Key Laboratory of Cardiovascular Disease, Fuzhou, Fujian, China
Center for Experimental Research in Clinical Medicine, Fujian Provincial Hospital, Fuzhou, Fujian, China
Central Laboratory, Fujian Provincial Hospital, Fuzhou, Fujian, China
Correspondence Yi Huang, Shengli Clinical Medical College, Fujian Medical University, Fujian, Fuzhou 350001, China.
Email: [email protected]
Search for more papers by this authorYi Zhang and Yuzhi Wang contributed equally to this work.
Abstract
Lung squamous cell carcinoma (LUSC) is one of the most common malignant tumors of the respiratory. Pyroptosis plays an essential role in cancer, but there is limited research investigating pyroptosis in LUSC. In this study, pyroptosis-related genes were observed to have extensive multiomics alterations in LUSC through analysis of the TCGA database. Utilizing machine learning for selection and verifying expression levels, GSDMC was chosen as the critical gene for further experiments. Our research found that GSDMC is overexpressed in LUSC tissues and cells, and is associated with poor prognosis. Knockdown of GSDMC in LUSC inhibits cell proliferation, invasion, metastasis, chemotherapeutic sensitivity, and reduced tumor formation in nude mice, accompanied by downregulation of proliferative and EMT-related protein expression. However, these effects were counteracted in cells where GSDMC is overexpressed. Mechanistically, the oncogenic role of GSDMC is primarily achieved through the activation of the AKT/mTOR pathway, and this effect can be significantly reversed by rapamycin. Finally, SMAD4's interaction with the promoter region of GSDMC results in the suppression of GSDMC expression. In summary, our study through bioinformatics and experimental approaches not only proves that SMAD4 regulates the protumorigenic role of GSDMC through transcriptional targeting, but also indicates the possibility of developing the SMAD4/GSDMC/AKT/mTOR signaling axis as a potential biomarker and treatment target for LUSC.
CONFLICT OF INTEREST STATEMENT
The authors declare no conflict of interest.
Open Research
DATA AVAILABILITY STATEMENT
The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author. The data that support the findings of this study are available from the corresponding author upon reasonable request.
Supporting Information
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Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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