RNF180 Inhibits Proliferation and Promotes Apoptosis of Colorectal Cancer Through Ubiquitination of WISP1
Colorectal cancer (CRC) is the third leading cause of cancer-related deaths globally and is biologically and clinically heterogeneous. Due to lack of gene expression signatures for risk and prognosis stratification of CRC, identifying novel molecular biomarkers and therapeutic targets may potentiall...
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Frontiers Media S.A.
2021-01-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2020.623455/full |
| _version_ | 1818414794427858944 |
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| author | Feng Wei Sang Ba Mei Jin Ren Ci Xuelian Wang Fusheng E Ziwen Long Ziwen Long |
| author_facet | Feng Wei Sang Ba Mei Jin Ren Ci Xuelian Wang Fusheng E Ziwen Long Ziwen Long |
| author_sort | Feng Wei |
| collection | DOAJ |
| description | Colorectal cancer (CRC) is the third leading cause of cancer-related deaths globally and is biologically and clinically heterogeneous. Due to lack of gene expression signatures for risk and prognosis stratification of CRC, identifying novel molecular biomarkers and therapeutic targets may potentially improve CRC prognosis and treatment. RNF180 has been shown to play key contributions to the development of several types of cancers. In the current study, we investigate its role in CRC. In this study, we show that RNF180 expression was significantly downregulated in human CRC tumors and cell lines. Overexpression of RNF180 in CRC cells markedly inhibited cell viability and induced cell apoptosis, while depletion of RNF180 dramatically enhanced cell survival. Moreover, WISP1 was found to be the critical downstream molecule that mediated the tumor suppressive effects of RNF180. Mechanistically, RNF180 ubiquitinated WISP1, resulting in WISP1 downregulation and ultimately leading to suppression of CRC tumor growth in patient-derived xenograft (PDX) mouse models. Last, 5-FU and RNF180 had synergetic effect on the apoptosis induction and tumor growth inhibition. Our findings revealed a crucial role of RNF180 in suppressing tumor growth by ubiquitinating WISP1 in CRC. |
| first_indexed | 2024-12-14T11:24:45Z |
| format | Article |
| id | doaj.art-2bfe9659fc8145ae82de07bc04763702 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-14T11:24:45Z |
| publishDate | 2021-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-2bfe9659fc8145ae82de07bc047637022022-12-21T23:03:34ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-01-01810.3389/fcell.2020.623455623455RNF180 Inhibits Proliferation and Promotes Apoptosis of Colorectal Cancer Through Ubiquitination of WISP1Feng Wei0Sang Ba1Mei Jin2Ren Ci3Xuelian Wang4Fusheng E5Ziwen Long6Ziwen Long7Department of Surgery, Shigatse People's Hospital, Shigatse, ChinaDepartment of Surgery, Shigatse People's Hospital, Shigatse, ChinaDepartment of Surgery, Shigatse People's Hospital, Shigatse, ChinaDepartment of Surgery, Shigatse People's Hospital, Shigatse, ChinaDepartment of Surgery, Shigatse People's Hospital, Shigatse, ChinaDepartment of Surgery, Shigatse People's Hospital, Shigatse, ChinaDepartment of Gastric Cancer Surgery, Fudan University Shanghai Cancer Center, Shanghai, ChinaDepartment of Oncology, Shanghai Medical College, Fudan University, Shanghai, ChinaColorectal cancer (CRC) is the third leading cause of cancer-related deaths globally and is biologically and clinically heterogeneous. Due to lack of gene expression signatures for risk and prognosis stratification of CRC, identifying novel molecular biomarkers and therapeutic targets may potentially improve CRC prognosis and treatment. RNF180 has been shown to play key contributions to the development of several types of cancers. In the current study, we investigate its role in CRC. In this study, we show that RNF180 expression was significantly downregulated in human CRC tumors and cell lines. Overexpression of RNF180 in CRC cells markedly inhibited cell viability and induced cell apoptosis, while depletion of RNF180 dramatically enhanced cell survival. Moreover, WISP1 was found to be the critical downstream molecule that mediated the tumor suppressive effects of RNF180. Mechanistically, RNF180 ubiquitinated WISP1, resulting in WISP1 downregulation and ultimately leading to suppression of CRC tumor growth in patient-derived xenograft (PDX) mouse models. Last, 5-FU and RNF180 had synergetic effect on the apoptosis induction and tumor growth inhibition. Our findings revealed a crucial role of RNF180 in suppressing tumor growth by ubiquitinating WISP1 in CRC.https://www.frontiersin.org/articles/10.3389/fcell.2020.623455/fullcolorectal cancerRNF180WISP15-fluorouracilubiquitination |
| spellingShingle | Feng Wei Sang Ba Mei Jin Ren Ci Xuelian Wang Fusheng E Ziwen Long Ziwen Long RNF180 Inhibits Proliferation and Promotes Apoptosis of Colorectal Cancer Through Ubiquitination of WISP1 Frontiers in Cell and Developmental Biology colorectal cancer RNF180 WISP1 5-fluorouracil ubiquitination |
| title | RNF180 Inhibits Proliferation and Promotes Apoptosis of Colorectal Cancer Through Ubiquitination of WISP1 |
| title_full | RNF180 Inhibits Proliferation and Promotes Apoptosis of Colorectal Cancer Through Ubiquitination of WISP1 |
| title_fullStr | RNF180 Inhibits Proliferation and Promotes Apoptosis of Colorectal Cancer Through Ubiquitination of WISP1 |
| title_full_unstemmed | RNF180 Inhibits Proliferation and Promotes Apoptosis of Colorectal Cancer Through Ubiquitination of WISP1 |
| title_short | RNF180 Inhibits Proliferation and Promotes Apoptosis of Colorectal Cancer Through Ubiquitination of WISP1 |
| title_sort | rnf180 inhibits proliferation and promotes apoptosis of colorectal cancer through ubiquitination of wisp1 |
| topic | colorectal cancer RNF180 WISP1 5-fluorouracil ubiquitination |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2020.623455/full |
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