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TRIM45 Suppresses the Development of Non-small Cell Lung Cancer

[ Vol. 20 , Issue. 4 ]

Author(s):

Xiyang Peng, Yao Wen, Lagabaiyila Zha, Jian Zhuang, Li Lin, Xu Li, Yu Chen, Zhiqiang Liu, Shuangli Zhu, Jifeng Liang, Zuoqiong Zhou, Wuzhou Yuan, Yongqing Li, Yuequn Wang, Zhigang Jiang, Xiaoyang Mo, Yongqi Wan, Yan Shi, Ping Zhu, Lan Zheng*, Changfa Tang*, Xiushan Wu* and Xiongwei Fan*   Pages 298 - 305 ( 8 )

Abstract:


Background: Previously, we first identified the human tripartite motifcontaining protein 45 (TRIM45) acts as a novel transcriptional repressor in mitogenactivated protein kinase (MAPK) signaling pathway. After that, the inhibitory role of TRIM45 in the development of tumor was gradually unveiled. However, the function of TRIM45 in the tumorigenesis of lung cancer has not been characterized.

Results: In this study, we found that TRIM45 was up-regulated in early-stage human non-small-cell lung cancer (NSCLC) tissues. Overexpression of TRIM45 in lung cancer cells induces G1 arrest and promotes apoptosis, which accompanied by up-regulated expression of RB, p16, p53, p27Kip1, and Caspase3 and down-regulated expression of CyclinE1 and CyclinE2. Further detection of the expression of the molecules in the MAPK signaling pathway revealed that overexpression of TRIM45 in lung cancer cells promotes phosphorylated p38 (p-p38) activation and inhibits phosphorylated ERK (p- ERK) activation. In accordance with this, p-p38 is increased while p-ERK is decreased in lung cancer tissues.

Conclusion: These findings indicate that TRIM45 plays an inhibitory role in the tumorigenesis of lung cancer. High-level expression of TRIM45 in lung cancer tissue may promote cell apoptosis by activating p38 signal and inhibit proliferation by down-regulating p-ERK, which provides a new clue for understanding the tumorigenesis of lung cancer.

Keywords:

TRIM45, NSCLC, lung cancer, apoptosis, inhibitory role, MAPK pathway.

Affiliation:

Key Laboratory of Physical Fitness and Exercise Rehabilitation of Hunan Province, College of Physical Education, Hunan Normal University, Changsha, Hunan 410012, The Center for Heart Development, State Key Laboratory of Development Biology of Freshwater Fish, Key Laboratory of MOE for Development Biology and Protein Chemistry, The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, Department of Forensic Science, School of Basic Medical Sciences, Central South University, Changsha 410013, Hunan, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510100, The Center for Heart Development, State Key Laboratory of Development Biology of Freshwater Fish, Key Laboratory of MOE for Development Biology and Protein Chemistry, The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, The Second Department of Thoracic Surgery, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xianga School of Medicine, Central South University, Changsha, Hunan 410013, The Center for Heart Development, State Key Laboratory of Development Biology of Freshwater Fish, Key Laboratory of MOE for Development Biology and Protein Chemistry, The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, The Center for Heart Development, State Key Laboratory of Development Biology of Freshwater Fish, Key Laboratory of MOE for Development Biology and Protein Chemistry, The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, The Center for Heart Development, State Key Laboratory of Development Biology of Freshwater Fish, Key Laboratory of MOE for Development Biology and Protein Chemistry, The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, The Center for Heart Development, State Key Laboratory of Development Biology of Freshwater Fish, Key Laboratory of MOE for Development Biology and Protein Chemistry, The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510100, The Center for Heart Development, State Key Laboratory of Development Biology of Freshwater Fish, Key Laboratory of MOE for Development Biology and Protein Chemistry, The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, The Center for Heart Development, State Key Laboratory of Development Biology of Freshwater Fish, Key Laboratory of MOE for Development Biology and Protein Chemistry, The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, The Center for Heart Development, State Key Laboratory of Development Biology of Freshwater Fish, Key Laboratory of MOE for Development Biology and Protein Chemistry, The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, The Center for Heart Development, State Key Laboratory of Development Biology of Freshwater Fish, Key Laboratory of MOE for Development Biology and Protein Chemistry, The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, The Center for Heart Development, State Key Laboratory of Development Biology of Freshwater Fish, Key Laboratory of MOE for Development Biology and Protein Chemistry, The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, The Center for Heart Development, State Key Laboratory of Development Biology of Freshwater Fish, Key Laboratory of MOE for Development Biology and Protein Chemistry, The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, The Center for Heart Development, State Key Laboratory of Development Biology of Freshwater Fish, Key Laboratory of MOE for Development Biology and Protein Chemistry, The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510100, Key Laboratory of Physical Fitness and Exercise Rehabilitation of Hunan Province, College of Physical Education, Hunan Normal University, Changsha, Hunan 410012, Key Laboratory of Physical Fitness and Exercise Rehabilitation of Hunan Province, College of Physical Education, Hunan Normal University, Changsha, Hunan 410012, The Center for Heart Development, State Key Laboratory of Development Biology of Freshwater Fish, Key Laboratory of MOE for Development Biology and Protein Chemistry, The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, The Center for Heart Development, State Key Laboratory of Development Biology of Freshwater Fish, Key Laboratory of MOE for Development Biology and Protein Chemistry, The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081



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