Operative ubiquitin-specific protease 22 deubiquitination confers a more invasive phenotype to cholangiocarcinoma
Oncogenic ubiquitin-specific protease 22 (USP22) is implicated in a variety of tumours; however, evidence of its role and underlying molecular mechanisms in cholangiocarcinoma (CCA) development remains unknown. We collected paired tumour and adjacent non-tumour tissues from 57 intrahepatic CCA (iCCA...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
Springer Nature
2021
|
| _version_ | 1797108967216775168 |
|---|---|
| author | Tian, Y Tang, B Wang, C Wang, Y Mao, J Yao, Y Gao, Z Liang, R Ye, M Cai, S Wang, L |
| author_facet | Tian, Y Tang, B Wang, C Wang, Y Mao, J Yao, Y Gao, Z Liang, R Ye, M Cai, S Wang, L |
| author_sort | Tian, Y |
| collection | OXFORD |
| description | Oncogenic ubiquitin-specific protease 22 (USP22) is implicated in a variety of tumours; however, evidence of its role and underlying molecular mechanisms in cholangiocarcinoma (CCA) development remains unknown. We collected paired tumour and adjacent non-tumour tissues from 57 intrahepatic CCA (iCCA) patients and evaluated levels of the USP22 gene and protein by qPCR and immunohistochemistry. Both the mRNA and protein were significantly upregulated, correlated with the malignant invasion and worse OS of iCCA. In cell cultures, USP22 overexpression increased CCA cell proliferation and mobility, and induced epithelial-to-mesenchymal transition (EMT). Upon an interaction, USP22 deubiquitinated and stabilized sirtuin-1 (SIRT1), in conjunction with Akt/ERK activation. In implantation xenografts, USP22 overexpression stimulated tumour growth and metastasis to the lungs of mice. Conversely, the knockdown by USP22 shRNA attenuated the tumour growth and invasiveness in vitro and in vivo. Furthermore, SIRT1 overexpression reversed the USP22 functional deficiency, while the knockdown acetylated TGF-β-activated kinase 1 (TAK1) and Akt. Our present study defines USP22 as a poor prognostic predictor in iCCA that cooperates with SIRT1 and facilitates tumour development. |
| first_indexed | 2024-03-07T07:35:23Z |
| format | Journal article |
| id | oxford-uuid:bded02a0-504f-4180-bfaf-905389ea6066 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:35:23Z |
| publishDate | 2021 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:bded02a0-504f-4180-bfaf-905389ea60662023-02-23T10:50:36ZOperative ubiquitin-specific protease 22 deubiquitination confers a more invasive phenotype to cholangiocarcinomaJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:bded02a0-504f-4180-bfaf-905389ea6066EnglishSymplectic ElementsSpringer Nature2021Tian, YTang, BWang, CWang, YMao, JYao, YGao, ZLiang, RYe, MCai, SWang, LOncogenic ubiquitin-specific protease 22 (USP22) is implicated in a variety of tumours; however, evidence of its role and underlying molecular mechanisms in cholangiocarcinoma (CCA) development remains unknown. We collected paired tumour and adjacent non-tumour tissues from 57 intrahepatic CCA (iCCA) patients and evaluated levels of the USP22 gene and protein by qPCR and immunohistochemistry. Both the mRNA and protein were significantly upregulated, correlated with the malignant invasion and worse OS of iCCA. In cell cultures, USP22 overexpression increased CCA cell proliferation and mobility, and induced epithelial-to-mesenchymal transition (EMT). Upon an interaction, USP22 deubiquitinated and stabilized sirtuin-1 (SIRT1), in conjunction with Akt/ERK activation. In implantation xenografts, USP22 overexpression stimulated tumour growth and metastasis to the lungs of mice. Conversely, the knockdown by USP22 shRNA attenuated the tumour growth and invasiveness in vitro and in vivo. Furthermore, SIRT1 overexpression reversed the USP22 functional deficiency, while the knockdown acetylated TGF-β-activated kinase 1 (TAK1) and Akt. Our present study defines USP22 as a poor prognostic predictor in iCCA that cooperates with SIRT1 and facilitates tumour development. |
| spellingShingle | Tian, Y Tang, B Wang, C Wang, Y Mao, J Yao, Y Gao, Z Liang, R Ye, M Cai, S Wang, L Operative ubiquitin-specific protease 22 deubiquitination confers a more invasive phenotype to cholangiocarcinoma |
| title | Operative ubiquitin-specific protease 22 deubiquitination confers a more invasive phenotype to cholangiocarcinoma |
| title_full | Operative ubiquitin-specific protease 22 deubiquitination confers a more invasive phenotype to cholangiocarcinoma |
| title_fullStr | Operative ubiquitin-specific protease 22 deubiquitination confers a more invasive phenotype to cholangiocarcinoma |
| title_full_unstemmed | Operative ubiquitin-specific protease 22 deubiquitination confers a more invasive phenotype to cholangiocarcinoma |
| title_short | Operative ubiquitin-specific protease 22 deubiquitination confers a more invasive phenotype to cholangiocarcinoma |
| title_sort | operative ubiquitin specific protease 22 deubiquitination confers a more invasive phenotype to cholangiocarcinoma |
| work_keys_str_mv | AT tiany operativeubiquitinspecificprotease22deubiquitinationconfersamoreinvasivephenotypetocholangiocarcinoma AT tangb operativeubiquitinspecificprotease22deubiquitinationconfersamoreinvasivephenotypetocholangiocarcinoma AT wangc operativeubiquitinspecificprotease22deubiquitinationconfersamoreinvasivephenotypetocholangiocarcinoma AT wangy operativeubiquitinspecificprotease22deubiquitinationconfersamoreinvasivephenotypetocholangiocarcinoma AT maoj operativeubiquitinspecificprotease22deubiquitinationconfersamoreinvasivephenotypetocholangiocarcinoma AT yaoy operativeubiquitinspecificprotease22deubiquitinationconfersamoreinvasivephenotypetocholangiocarcinoma AT gaoz operativeubiquitinspecificprotease22deubiquitinationconfersamoreinvasivephenotypetocholangiocarcinoma AT liangr operativeubiquitinspecificprotease22deubiquitinationconfersamoreinvasivephenotypetocholangiocarcinoma AT yem operativeubiquitinspecificprotease22deubiquitinationconfersamoreinvasivephenotypetocholangiocarcinoma AT cais operativeubiquitinspecificprotease22deubiquitinationconfersamoreinvasivephenotypetocholangiocarcinoma AT wangl operativeubiquitinspecificprotease22deubiquitinationconfersamoreinvasivephenotypetocholangiocarcinoma |