2. Academic Validation
  3. Pyroptosis-related gene GSDMC indicates poor prognosis and promotes tumor progression by activating the AKT/mTOR pathway in lung squamous cell carcinoma

Pyroptosis-related gene GSDMC indicates poor prognosis and promotes tumor progression by activating the AKT/mTOR pathway in lung squamous cell carcinoma

  • Mol Carcinog. 2024 Aug 13. doi: 10.1002/mc.23805.
Yi Zhang 1 2,  Yuzhi Wang 3,  Jiamiao Weng 1 2,  Jianlin Chen 1 2,  Yue Zheng 1 2,  Yu Xia 2 4,  Zhixin Huang 2 4,  Lilan Zhao 1 5,  Xiongfeng Chen 1 6,  Haijun Tang 1 7,  Yi Huang 1 2 7 8 9
Affiliations

Affiliations

  • 1 Shengli Clinical Medical College, Fujian Medical University, Fuzhou, Fujian, China.
  • 2 Department of Clinical Laboratory, Fujian Provincial Hospital, Fuzhou, Fujian, China.
  • 3 Department of Laboratory Medicine, Deyang People's Hospital, Deyang, Sichuan, China.
  • 4 Integrated Chinese and Western Medicine College, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China.
  • 5 Department of General Thoracic Surgery, Fujian Provincial Hospital, Fujian Medical University, Fuzhou, Fujian, China.
  • 6 Department of Scientific Research, Fujian Provincial Hospital, Fuzhou, Fujian, China.
  • 7 Fujian Provincial Key Laboratory of Critical Care Medicine, Fujian Provincial Key Laboratory of Cardiovascular Disease, Fuzhou, Fujian, China.
  • 8 Center for Experimental Research in Clinical Medicine, Fujian Provincial Hospital, Fuzhou, Fujian, China.
  • 9 Central Laboratory, Fujian Provincial Hospital, Fuzhou, Fujian, China.
PMID: 39136610 DOI: 10.1002/mc.23805
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.

Keywords

GSDMC; SMAD4; lung squamous cell carcinoma; mTOR; pyroptosis.

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