Elevated TRIM44 promotes intrahepatic cholangiocarcinoma progression by inducing cell EMT via MAPK signaling
Abstract Surgical results for intrahepatic cholangiocarcinoma (ICC) remain unsatisfactory due to the high rate of recurrence. Here, we investigated that the expression and roles of tripartite motif‐containing protein 44 (TRIM44) in human ICCs. Firstly, TRIM44 expression was analyzed in several kinds...
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| Format: | Article |
| Language: | English |
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Wiley
2018-03-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.1313 |
| _version_ | 1797390103434231808 |
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| author | Rui Peng Peng‐Fei Zhang Chi Zhang Xiao‐Yong Huang Yan‐bing Ding Bin Deng Dou‐Sheng Bai Ya‐Ping Xu |
| author_facet | Rui Peng Peng‐Fei Zhang Chi Zhang Xiao‐Yong Huang Yan‐bing Ding Bin Deng Dou‐Sheng Bai Ya‐Ping Xu |
| author_sort | Rui Peng |
| collection | DOAJ |
| description | Abstract Surgical results for intrahepatic cholangiocarcinoma (ICC) remain unsatisfactory due to the high rate of recurrence. Here, we investigated that the expression and roles of tripartite motif‐containing protein 44 (TRIM44) in human ICCs. Firstly, TRIM44 expression was analyzed in several kinds of cancers by referring to public Oncomine database, and the expressions of TRIM44 mRNA and protein were tested in ICC and corresponding paratumorous tissues. Secondly, functions and mechanisms of TRIM44 in ICC cells were further evaluated by TRIM44 interference and cDNA transfection. Finally, the prognostic role of TRIM44 was assessed by Kaplan–Meier and Cox regression. We found that TRIM44 expression was upregulated in ICC tissues compared with corresponding paratumorous tissues, which were consistent with the results from the public cancer database. Knockdown of TRIM44 repressed the invasion and migration of ICC cells, while increased the ICC cell apoptosis. Additionally, high level of TRIM44 was shown to induce ICC cell epithelial to mesenchymal transition (EMT). Mechanistically, a high level of TRIM44 was found to activate MAPK signaling, and a MEK inhibitor, AZD6244, reversed cell EMT and apoptosis endowed by TRIM44 overexpression. Clinically, TRIM44 expression was positively associated with large tumor size (P = 0.035), lymphatic metastasis (P = 0.008) and poor tumor differentiation (P = 0.036). Importantly, patients in TRIM44high group had shorter overall survival and higher cumulative rate of recurrence than patients in TRIM44low group. Our results suggest elevated TRIM44 promotes ICC development by inducing cell EMT and apoptosis resistance, and TRIM44 is a valuable prognostic biomarker and promising therapeutic target of ICC. |
| first_indexed | 2024-03-08T23:06:45Z |
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| id | doaj.art-ba8a1d368f6a43f6bdf1f6952e978619 |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-03-08T23:06:45Z |
| publishDate | 2018-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-ba8a1d368f6a43f6bdf1f6952e9786192023-12-15T12:32:12ZengWileyCancer Medicine2045-76342018-03-017379680810.1002/cam4.1313Elevated TRIM44 promotes intrahepatic cholangiocarcinoma progression by inducing cell EMT via MAPK signalingRui Peng0Peng‐Fei Zhang1Chi Zhang2Xiao‐Yong Huang3Yan‐bing Ding4Bin Deng5Dou‐Sheng Bai6Ya‐Ping Xu7Department of Gastroenterology Shanghai Tenth People's Hospital Tongji University School of Medicine Shanghai 200032 ChinaDepartment of Gastroenterology Shanghai Tenth People's Hospital Tongji University School of Medicine Shanghai 200032 ChinaDepartment of Hepatobiliary and Pancreatic Surgery Subei People's Hospital Clinical Medical School Yangzhou University Affiliated Hospital Yangzhou ChinaLiver Cancer Institute Ministry of Education Zhongshan Hospital Fudan University Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University) Shanghai 200032 ChinaDepartment of Gastroenterology Yangzhou No. 1, People's Hospital The Second Clinical School of Yangzhou University Yangzhou ChinaDepartment of Gastroenterology Yangzhou No. 1, People's Hospital The Second Clinical School of Yangzhou University Yangzhou ChinaDepartment of Hepatobiliary and Pancreatic Surgery Subei People's Hospital Clinical Medical School Yangzhou University Affiliated Hospital Yangzhou ChinaDepartment of Gastroenterology Shanghai Tenth People's Hospital Tongji University School of Medicine Shanghai 200032 ChinaAbstract Surgical results for intrahepatic cholangiocarcinoma (ICC) remain unsatisfactory due to the high rate of recurrence. Here, we investigated that the expression and roles of tripartite motif‐containing protein 44 (TRIM44) in human ICCs. Firstly, TRIM44 expression was analyzed in several kinds of cancers by referring to public Oncomine database, and the expressions of TRIM44 mRNA and protein were tested in ICC and corresponding paratumorous tissues. Secondly, functions and mechanisms of TRIM44 in ICC cells were further evaluated by TRIM44 interference and cDNA transfection. Finally, the prognostic role of TRIM44 was assessed by Kaplan–Meier and Cox regression. We found that TRIM44 expression was upregulated in ICC tissues compared with corresponding paratumorous tissues, which were consistent with the results from the public cancer database. Knockdown of TRIM44 repressed the invasion and migration of ICC cells, while increased the ICC cell apoptosis. Additionally, high level of TRIM44 was shown to induce ICC cell epithelial to mesenchymal transition (EMT). Mechanistically, a high level of TRIM44 was found to activate MAPK signaling, and a MEK inhibitor, AZD6244, reversed cell EMT and apoptosis endowed by TRIM44 overexpression. Clinically, TRIM44 expression was positively associated with large tumor size (P = 0.035), lymphatic metastasis (P = 0.008) and poor tumor differentiation (P = 0.036). Importantly, patients in TRIM44high group had shorter overall survival and higher cumulative rate of recurrence than patients in TRIM44low group. Our results suggest elevated TRIM44 promotes ICC development by inducing cell EMT and apoptosis resistance, and TRIM44 is a valuable prognostic biomarker and promising therapeutic target of ICC.https://doi.org/10.1002/cam4.1313ApoptosisEMTICCprognosisTRIM44 |
| spellingShingle | Rui Peng Peng‐Fei Zhang Chi Zhang Xiao‐Yong Huang Yan‐bing Ding Bin Deng Dou‐Sheng Bai Ya‐Ping Xu Elevated TRIM44 promotes intrahepatic cholangiocarcinoma progression by inducing cell EMT via MAPK signaling Cancer Medicine Apoptosis EMT ICC prognosis TRIM44 |
| title | Elevated TRIM44 promotes intrahepatic cholangiocarcinoma progression by inducing cell EMT via MAPK signaling |
| title_full | Elevated TRIM44 promotes intrahepatic cholangiocarcinoma progression by inducing cell EMT via MAPK signaling |
| title_fullStr | Elevated TRIM44 promotes intrahepatic cholangiocarcinoma progression by inducing cell EMT via MAPK signaling |
| title_full_unstemmed | Elevated TRIM44 promotes intrahepatic cholangiocarcinoma progression by inducing cell EMT via MAPK signaling |
| title_short | Elevated TRIM44 promotes intrahepatic cholangiocarcinoma progression by inducing cell EMT via MAPK signaling |
| title_sort | elevated trim44 promotes intrahepatic cholangiocarcinoma progression by inducing cell emt via mapk signaling |
| topic | Apoptosis EMT ICC prognosis TRIM44 |
| url | https://doi.org/10.1002/cam4.1313 |
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