Chang Gu1, Zhenyu Huang2, Xiaojian Chen3, Chenying Liu3, Gaetano Rocco4, Shengnan Zhao5, Huikang Xie5, Jiafei Chen1, Chenyang Dai6, Chang Chen7. 1. Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China. 2. Department of Colorectal and Anal Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 200092 Shanghai, China; Shanghai Colorectal Cancer Research Center, 200092, Shanghai, China. Electronic address: huangzyu@outlook.com. 3. Department of Colorectal and Anal Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 200092 Shanghai, China; Shanghai Colorectal Cancer Research Center, 200092, Shanghai, China. 4. Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, United States of America; Druckenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY, United States of America. 5. Department of Pathology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China. 6. Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China. Electronic address: daichenyang@tongji.edu.cn. 7. Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China. Electronic address: chenthoracic@126.com.
Abstract
OBJECTIVE: Whether TEAD4 itself plays a vital role in the tumorigenesis and development of lung adenocarcinoma remains unclear. In our study, we aim to investigate the expression pattern and biological functions of TEAD4 and further investigate the potential mechanisms. METHODS: Clinical tumor and paired normal samples were collected for preparing tissue microarray. Western blot and immunohistochemical (IHC) staining of TEAD4 expression in these tissues were conducted to explore the expression pattern. Moreover, A549 cell line was select for investigating the function of TEAD4 for lung adenocarcinoma in vitro and in vivo. RNA sequencing was finally performed to further detect the potential downstream genes. RESULTS: The elevated TEAD4 expression level was observed in tumor tissues and the patients with higher TEAD4 expression tended to have worse overall survival. The knockdown of TEAD4 inhibits A549 cells proliferation ability and migration ability. A total of 431 differentially expressed genes (DEGs), including 239 down-regulated genes and 191 up-regulated genes, were finally identified and some of DEGs were validated. Moreover, knockdown of TEAD4 led to the down-regulation of pERK, which maybe the potential TEAD4-targeted signaling pathway to play the pro-tumorigenic function. CONCLUSIONS: The expression level of TEAD4 is high in lung adenocarcinoma tumor tissues and positively associated with worse prognosis. Up-regulation of TEAD4 may lead to excessive transcription and phosphorylation of ERK proteins and therefore accelerates the process of tumor development. Our results demonstrate that overexpression of TEAD4 is a new mechanism of dysregulation of Hippo pathway.
OBJECTIVE: Whether TEAD4 itself plays a vital role in the tumorigenesis and development of lung adenocarcinoma remains unclear. In our study, we aim to investigate the expression pattern and biological functions of TEAD4 and further investigate the potential mechanisms. METHODS: Clinical tumor and paired normal samples were collected for preparing tissue microarray. Western blot and immunohistochemical (IHC) staining of TEAD4 expression in these tissues were conducted to explore the expression pattern. Moreover, A549 cell line was select for investigating the function of TEAD4 for lung adenocarcinoma in vitro and in vivo. RNA sequencing was finally performed to further detect the potential downstream genes. RESULTS: The elevated TEAD4 expression level was observed in tumor tissues and the patients with higher TEAD4 expression tended to have worse overall survival. The knockdown of TEAD4 inhibits A549 cells proliferation ability and migration ability. A total of 431 differentially expressed genes (DEGs), including 239 down-regulated genes and 191 up-regulated genes, were finally identified and some of DEGs were validated. Moreover, knockdown of TEAD4 led to the down-regulation of pERK, which maybe the potential TEAD4-targeted signaling pathway to play the pro-tumorigenic function. CONCLUSIONS: The expression level of TEAD4 is high in lung adenocarcinoma tumor tissues and positively associated with worse prognosis. Up-regulation of TEAD4 may lead to excessive transcription and phosphorylation of ERK proteins and therefore accelerates the process of tumor development. Our results demonstrate that overexpression of TEAD4 is a new mechanism of dysregulation of Hippo pathway.
Authors: Xiaobin Zhang; Yi He; Haiyong Gu; Zhichao Liu; Bin Li; Yang Yang; Jie Hao; Rong Hua Journal: Front Genet Date: 2021-05-19 Impact factor: 4.599
Authors: Zhiqiang Wang; Zhongjun Ding; Yan Guan; Chunhui Liu; Linjun Wang; Wensheng Shan; Jie Yang Journal: Comput Math Methods Med Date: 2021-06-09 Impact factor: 2.238