FBXO2 Promotes Proliferation of Endometrial Cancer by Ubiquitin-Mediated Degradation of FBN1 in the Regulation of the Cell Cycle and the Autophagy Pathway
F-box proteins, as substrates for S phase kinase-associated protein 1 (SKP1)-cullin 1 (CUL1)-F-box protein (SCF) ubiquitin ligase complexes, mediate the degradation of a large number of regulatory proteins involved in cancer processes. In this study, we found that F-box only protein 2 (FBXO2) was up...
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Frontiers Media S.A.
2020-08-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fcell.2020.00843/full |
| _version_ | 1818404603692056576 |
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| author | Xiaoxia Che Xiaoxia Che Fangfang Jian Ying Wang Jingjing Zhang Jian Shen Qi Cheng Xi Wang Nan Jia Weiwei Feng |
| author_facet | Xiaoxia Che Xiaoxia Che Fangfang Jian Ying Wang Jingjing Zhang Jian Shen Qi Cheng Xi Wang Nan Jia Weiwei Feng |
| author_sort | Xiaoxia Che |
| collection | DOAJ |
| description | F-box proteins, as substrates for S phase kinase-associated protein 1 (SKP1)-cullin 1 (CUL1)-F-box protein (SCF) ubiquitin ligase complexes, mediate the degradation of a large number of regulatory proteins involved in cancer processes. In this study, we found that F-box only protein 2 (FBXO2) was up-regulated in 21 endometrial carcinoma (EC) samples compared with five normal endometrium samples based on our Fudan cohort RNA-sequencing. The increased FBXO2 expression was associated with tumor stage, tumor grade, and histologic tumor type, and poor prognosis based on The Cancer Genome Atlas (TCGA) database. FBXO2 knockdown inhibited EC cell proliferation, and FBXO2 overexpression promoted the parental cell phenotype in vivo and in vitro. Fibrillin1 (FBN1) was also identified as a substrate for FBXO2 using a ubiquitination-proteome approach. In addition, promotion of EC proliferation by FBXO2 was regulated by specific proteins of the cell cycle (CDK4, CyclinD1, CyclinD2, and CyclinA1) and the autophagy signaling pathway (ATG4A and ATG4D) based on RNA sequencing (RNA-seq). We concluded that FBXO2 acts as an E3 ligase that targets FBN1 for ubiquitin-dependent degradation, so as to promote EC proliferation by regulating the cell cycle and the autophagy signaling pathway. Targeting FBXO2 may represent a potential therapeutic target for EC. |
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| id | doaj.art-72472b7a14c94daa8d5fa76ece93a47a |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-14T08:42:47Z |
| publishDate | 2020-08-01 |
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| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-72472b7a14c94daa8d5fa76ece93a47a2022-12-21T23:09:15ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2020-08-01810.3389/fcell.2020.00843568564FBXO2 Promotes Proliferation of Endometrial Cancer by Ubiquitin-Mediated Degradation of FBN1 in the Regulation of the Cell Cycle and the Autophagy PathwayXiaoxia Che0Xiaoxia Che1Fangfang Jian2Ying Wang3Jingjing Zhang4Jian Shen5Qi Cheng6Xi Wang7Nan Jia8Weiwei Feng9Department of Obstetrics and Gynecology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaObstetrics and Gynecology Hospital, Fudan University, Shanghai, ChinaDepartment of Obstetrics and Gynecology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Obstetrics and Gynecology, Yidu Central Hospital of Weifang, Weifang, ChinaDepartment of Obstetrics and Gynecology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Obstetrics and Gynecology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaObstetrics and Gynecology Hospital, Fudan University, Shanghai, ChinaObstetrics and Gynecology Hospital, Fudan University, Shanghai, ChinaObstetrics and Gynecology Hospital, Fudan University, Shanghai, ChinaDepartment of Obstetrics and Gynecology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaF-box proteins, as substrates for S phase kinase-associated protein 1 (SKP1)-cullin 1 (CUL1)-F-box protein (SCF) ubiquitin ligase complexes, mediate the degradation of a large number of regulatory proteins involved in cancer processes. In this study, we found that F-box only protein 2 (FBXO2) was up-regulated in 21 endometrial carcinoma (EC) samples compared with five normal endometrium samples based on our Fudan cohort RNA-sequencing. The increased FBXO2 expression was associated with tumor stage, tumor grade, and histologic tumor type, and poor prognosis based on The Cancer Genome Atlas (TCGA) database. FBXO2 knockdown inhibited EC cell proliferation, and FBXO2 overexpression promoted the parental cell phenotype in vivo and in vitro. Fibrillin1 (FBN1) was also identified as a substrate for FBXO2 using a ubiquitination-proteome approach. In addition, promotion of EC proliferation by FBXO2 was regulated by specific proteins of the cell cycle (CDK4, CyclinD1, CyclinD2, and CyclinA1) and the autophagy signaling pathway (ATG4A and ATG4D) based on RNA sequencing (RNA-seq). We concluded that FBXO2 acts as an E3 ligase that targets FBN1 for ubiquitin-dependent degradation, so as to promote EC proliferation by regulating the cell cycle and the autophagy signaling pathway. Targeting FBXO2 may represent a potential therapeutic target for EC.https://www.frontiersin.org/article/10.3389/fcell.2020.00843/fullendometrial carcinomaFBXO2FBN1ubiquitinationcell cycleautophagy |
| spellingShingle | Xiaoxia Che Xiaoxia Che Fangfang Jian Ying Wang Jingjing Zhang Jian Shen Qi Cheng Xi Wang Nan Jia Weiwei Feng FBXO2 Promotes Proliferation of Endometrial Cancer by Ubiquitin-Mediated Degradation of FBN1 in the Regulation of the Cell Cycle and the Autophagy Pathway Frontiers in Cell and Developmental Biology endometrial carcinoma FBXO2 FBN1 ubiquitination cell cycle autophagy |
| title | FBXO2 Promotes Proliferation of Endometrial Cancer by Ubiquitin-Mediated Degradation of FBN1 in the Regulation of the Cell Cycle and the Autophagy Pathway |
| title_full | FBXO2 Promotes Proliferation of Endometrial Cancer by Ubiquitin-Mediated Degradation of FBN1 in the Regulation of the Cell Cycle and the Autophagy Pathway |
| title_fullStr | FBXO2 Promotes Proliferation of Endometrial Cancer by Ubiquitin-Mediated Degradation of FBN1 in the Regulation of the Cell Cycle and the Autophagy Pathway |
| title_full_unstemmed | FBXO2 Promotes Proliferation of Endometrial Cancer by Ubiquitin-Mediated Degradation of FBN1 in the Regulation of the Cell Cycle and the Autophagy Pathway |
| title_short | FBXO2 Promotes Proliferation of Endometrial Cancer by Ubiquitin-Mediated Degradation of FBN1 in the Regulation of the Cell Cycle and the Autophagy Pathway |
| title_sort | fbxo2 promotes proliferation of endometrial cancer by ubiquitin mediated degradation of fbn1 in the regulation of the cell cycle and the autophagy pathway |
| topic | endometrial carcinoma FBXO2 FBN1 ubiquitination cell cycle autophagy |
| url | https://www.frontiersin.org/article/10.3389/fcell.2020.00843/full |
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