Wenzheng Guo1, Min Hu2, Jingjing Wu3, Aiping Zhou4, Yueling Liao5, Hongyong Song6, Dongliang Xu7, Yanbin Kuang8, Tong Wang9, Bo Jing10, Kaimi Li11, Jing Ling12, Donghua Wen13, Wenjuan Wu14. 1. Department of Laboratory Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China. Electronic address: guowenzheng801@126.com. 2. Key Laboratory of Cell Differentiation and Apoptosis of Chinese Minister of Education, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: 274169714@qq.com. 3. Department of Laboratory Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China. Electronic address: wujingjing802@126.com. 4. Department of Laboratory Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China. Electronic address: abby_aiping@126.com. 5. Key Laboratory of Cell Differentiation and Apoptosis of Chinese Minister of Education, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: lylsolo@126.com. 6. Key Laboratory of Cell Differentiation and Apoptosis of Chinese Minister of Education, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: hysong2003@126.com. 7. Key Laboratory of Cell Differentiation and Apoptosis of Chinese Minister of Education, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: yookagi@163.com. 8. Department of Respiratory Medicine, The Second Affiliated Hospital, Dalian Medical University, Dalian, China. Electronic address: kybkyb2@163.com. 9. Key Laboratory of Cell Differentiation and Apoptosis of Chinese Minister of Education, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: 1107114720@qq.com. 10. Key Laboratory of Cell Differentiation and Apoptosis of Chinese Minister of Education, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: 15000036395@163.com. 11. Key Laboratory of Cell Differentiation and Apoptosis of Chinese Minister of Education, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: 18234118361@163.com. 12. Key Laboratory of Cell Differentiation and Apoptosis of Chinese Minister of Education, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. 13. Department of Laboratory Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China. Electronic address: wdhalan@163.com. 14. Department of Laboratory Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China. Electronic address: wwj1210@126.com.
Abstract
AIMS: Lung cancer remains the leading cause of cancer incidence and mortality. Although cigarette smoke is regarded as a high risk factor for lung tumor initiation, the role of the lung tumor suppressor GPRC5A in smoking-induced lung cancer is unclear. MAIN METHODS: We obtained two lung cancer cohorts from the TCGA and GEO databases. Bioinformatics analysis showed differential gene expression in the cohorts. Quantitative real-time PCR, Western Blot and Gprc5a-/- mice uncovered the relationship between cigarette smoke and lung cancer in the GPRC5A deletion system in vitro and in vivo. KEY FINDINGS: Bioinformatics analysis showed that the smoking lung cancer patients with low expression of GPRC5A had poor overall survival compared to the patients with high GPRC5A expression. Further analysis revealed that cancer-related stemness pathways such as the Hippo signaling pathway were induced in smoking patients with low GPRC5A expression. Additionally, we detected enriched expression of WNT5A and DLX5 in normal human lung epithelial 16HBE cells and human lung cancer H1299 cells in vitro. A relationship between cigarette smoke extract (NNK) and lung tumor initiation was observed in Gprc5a-/- mice. SIGNIFICANCE: The lung tumor suppressor gene GPRC5A played a protective role in cigarette smoke-induced lung tumor initiation, providing a target for the prevention of lung cancer development and monitoring of prognosis.
AIMS: Lung cancer remains the leading cause of cancer incidence and mortality. Although cigarette smoke is regarded as a high risk factor for lung tumor initiation, the role of the lung tumor suppressor GPRC5A in smoking-induced lung cancer is unclear. MAIN METHODS: We obtained two lung cancer cohorts from the TCGA and GEO databases. Bioinformatics analysis showed differential gene expression in the cohorts. Quantitative real-time PCR, Western Blot and Gprc5a-/- mice uncovered the relationship between cigarette smoke and lung cancer in the GPRC5A deletion system in vitro and in vivo. KEY FINDINGS: Bioinformatics analysis showed that the smoking lung cancerpatients with low expression of GPRC5A had poor overall survival compared to the patients with high GPRC5A expression. Further analysis revealed that cancer-related stemness pathways such as the Hippo signaling pathway were induced in smoking patients with low GPRC5A expression. Additionally, we detected enriched expression of WNT5A and DLX5 in normal human lung epithelial 16HBE cells and humanlung cancer H1299 cells in vitro. A relationship between cigarette smoke extract (NNK) and lung tumor initiation was observed in Gprc5a-/- mice. SIGNIFICANCE: The lung tumor suppressor gene GPRC5A played a protective role in cigarette smoke-induced lung tumor initiation, providing a target for the prevention of lung cancer development and monitoring of prognosis.
Authors: Yu-Hang Zhang; Michael R Hoopmann; Peter J Castaldi; Kirsten A Simonsen; Mukul K Midha; Michael H Cho; Gerard J Criner; Raphael Bueno; Jiangyuan Liu; Robert L Moritz; Edwin K Silverman Journal: Am J Physiol Lung Cell Mol Physiol Date: 2021-10-20 Impact factor: 5.464
Authors: Zhou Jiawei; Mu Min; Xing Yingru; Zhang Xin; Li Danting; Liu Yafeng; Xie Jun; Hu Wangfa; Zhang Lijun; Wu Jing; Hu Dong Journal: Front Mol Biosci Date: 2020-10-27