Xiaoting Huang1,2, Leyang Xiang3, Baiyao Wang1,2, Jijie Hu4, Chunshan Liu1,2, Anbang Ren1,2, Kunpeng Du1,2, Gengtai Ye5, Yingying Liang1,2, Yunqiang Tang6, Dinghua Yang7, Yawei Yuan8,9. 1. Department of Radiation Oncology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, No. 78 Hengzhigang Road, Guangzhou, 510095, Guangdong, People's Republic of China. 2. State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Disease, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China. 3. Department of Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, No. 78 Hengzhigang Road, Guangzhou, 510095, Guangdong, People's Republic of China. 4. Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou, China. 5. Unit of Hepatobiliary Surgery, Department of General Surgery, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Baiyun District, Guangzhou, 510515, China. 6. Department of Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, No. 78 Hengzhigang Road, Guangzhou, 510095, Guangdong, People's Republic of China. gyzl_tang@126.com. 7. Unit of Hepatobiliary Surgery, Department of General Surgery, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Baiyun District, Guangzhou, 510515, China. dhyangyd@yahoo.com. 8. Department of Radiation Oncology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, No. 78 Hengzhigang Road, Guangzhou, 510095, Guangdong, People's Republic of China. yuanyawei@gzhmu.edu.cn. 9. State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Disease, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China. yuanyawei@gzhmu.edu.cn.
Abstract
BACKGROUND: CKLF like MARVEL transmembrane domain containing 6 (CMTM6) has been associated with the development in many kinds of cancers. However, the roles of CMTM6 in hepatocellular carcinoma (HCC) are largely unknown. Thus, the present study aimed to investigate the function of CMTM6 in HCC. METHODS: We analysed CMTM6 levels and functions using human HCC cell lines, paired HCC and adjacent non-tumorous tissues, and a tissue microarray. CMTM6 expression was silenced using short hairpin RNAs and its was overexpressed from a lentivirus vector. CMTM6 mRNA and protein levels were determined using quantitative real-time reverse transcription PCR and western blotting, respectively. Proliferation, colony formation, migration, and invasion were assessed using a Cell counting kit-8, colony formation, wound-healing, and Matrigel invasion assays, respectively. Immunohistochemistry was used to score the expression of CMTM6 in tissue samples. The localization and binding partners of CMTM6 were investigated using immunofluorescence and coimmunoprecipitation experiments, respectively. A mouse xenograft model was used for in vivo studies. RESULTS: Compared with that in adjacent, non-cancerous tissue, Here, CMTM6 levels were increased in HCC tissue samples. Silencing of CMTM6 suppressed the proliferation, migration, and invasion of HCC cells. Conversely, CMTM6 overexpression enhanced HCC cell invasion, migration, and proliferation. Mechanistically, CMTM6 physically interacts with and stabilizes vimentin, thus inducing epithelial-mesenchymal transition (EMT), which promotes proliferation, migration and invasion. Importantly, in HCC tissues, CMTM6 expression correlated positively with vimentin levels. Poor prognosis of HCC was associated significantly with higher CMTM6 expression. CONCLUSIONS: CMTM6 has an important function in HCC proliferation, migration, and invasion, via its interaction with and stabilization of vimentin. CMTM6 might represent a potential biomarker and therapeutic target to treat HCC.
BACKGROUND: CKLF like MARVEL transmembrane domain containing 6 (CMTM6) has been associated with the development in many kinds of cancers. However, the roles of CMTM6 in hepatocellular carcinoma (HCC) are largely unknown. Thus, the present study aimed to investigate the function of CMTM6 in HCC. METHODS: We analysed CMTM6 levels and functions using human HCC cell lines, paired HCC and adjacent non-tumorous tissues, and a tissue microarray. CMTM6 expression was silenced using short hairpin RNAs and its was overexpressed from a lentivirus vector. CMTM6 mRNA and protein levels were determined using quantitative real-time reverse transcription PCR and western blotting, respectively. Proliferation, colony formation, migration, and invasion were assessed using a Cell counting kit-8, colony formation, wound-healing, and Matrigel invasion assays, respectively. Immunohistochemistry was used to score the expression of CMTM6 in tissue samples. The localization and binding partners of CMTM6 were investigated using immunofluorescence and coimmunoprecipitation experiments, respectively. A mouse xenograft model was used for in vivo studies. RESULTS: Compared with that in adjacent, non-cancerous tissue, Here, CMTM6 levels were increased in HCC tissue samples. Silencing of CMTM6 suppressed the proliferation, migration, and invasion of HCC cells. Conversely, CMTM6 overexpression enhanced HCC cell invasion, migration, and proliferation. Mechanistically, CMTM6 physically interacts with and stabilizes vimentin, thus inducing epithelial-mesenchymal transition (EMT), which promotes proliferation, migration and invasion. Importantly, in HCC tissues, CMTM6 expression correlated positively with vimentin levels. Poor prognosis of HCC was associated significantly with higher CMTM6 expression. CONCLUSIONS: CMTM6 has an important function in HCC proliferation, migration, and invasion, via its interaction with and stabilization of vimentin. CMTM6 might represent a potential biomarker and therapeutic target to treat HCC.
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