The RNA-binding protein PCBP1 represses lung adenocarcinoma progression by stabilizing DKK1 mRNA and subsequently downregulating β-catenin
Abstract Background PolyC-RNA-binding protein 1 (PCBP1) functions as a tumour suppressor and RNA regulator that is downregulated in human cancers. Here, we aimed to reveal the biological function of PCBP1 in lung adenocarcinoma (LUAD). Methods First, PCBP1 was identified as an important biomarker th...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2022-07-01
|
| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-022-03552-y |
| _version_ | 1818163119590998016 |
|---|---|
| author | Yujia Zheng Zheng Zhou Ran Wei Chu Xiao Hao Zhang Tao Fan Bo Zheng Chunxiang Li Jie He |
| author_facet | Yujia Zheng Zheng Zhou Ran Wei Chu Xiao Hao Zhang Tao Fan Bo Zheng Chunxiang Li Jie He |
| author_sort | Yujia Zheng |
| collection | DOAJ |
| description | Abstract Background PolyC-RNA-binding protein 1 (PCBP1) functions as a tumour suppressor and RNA regulator that is downregulated in human cancers. Here, we aimed to reveal the biological function of PCBP1 in lung adenocarcinoma (LUAD). Methods First, PCBP1 was identified as an important biomarker that maintains LUAD through The Cancer Genome Atlas (TCGA) project screening and confirmed by immunohistochemistry and qPCR. Via colony formation, CCK8, IncuCyte cell proliferation, wound healing and Transwell assays, we confirmed that PCBP1 was closely related to the proliferation and migration of LUAD cells. The downstream gene DKK1 was discovered by RNA sequencing of PCBP1 knockdown cells. The underlying mechanisms were further investigated using western blot, qPCR, RIP, RNA pulldown and mRNA stability assays. Results We demonstrate that PCBP1 is downregulated in LUAD tumour tissues. The reduction in PCBP1 promotes the proliferation, migration and invasion of LUAD in vitro and in vivo. Mechanistically, the RNA-binding protein PCBP1 represses LUAD by stabilizing DKK1 mRNA. Subsequently, decreased expression of the DKK1 protein relieves the inhibitory effect on the Wnt/β-catenin signalling pathway. Taken together, these results show that PCBP1 acts as a tumour suppressor gene, inhibiting the tumorigenesis of LUAD. Conclusions We found that PCBP1 inhibits LUAD development by upregulating DKK1 to inactivate the Wnt/β-catenin pathway. Our findings highlight the potential of PCBP1 as a promising therapeutic target. |
| first_indexed | 2024-12-11T16:44:30Z |
| format | Article |
| id | doaj.art-f2405207c05848109ae77248b71bc6b7 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-12-11T16:44:30Z |
| publishDate | 2022-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-f2405207c05848109ae77248b71bc6b72022-12-22T00:58:15ZengBMCJournal of Translational Medicine1479-58762022-07-0120111810.1186/s12967-022-03552-yThe RNA-binding protein PCBP1 represses lung adenocarcinoma progression by stabilizing DKK1 mRNA and subsequently downregulating β-cateninYujia Zheng0Zheng Zhou1Ran Wei2Chu Xiao3Hao Zhang4Tao Fan5Bo Zheng6Chunxiang Li7Jie He8Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeAbstract Background PolyC-RNA-binding protein 1 (PCBP1) functions as a tumour suppressor and RNA regulator that is downregulated in human cancers. Here, we aimed to reveal the biological function of PCBP1 in lung adenocarcinoma (LUAD). Methods First, PCBP1 was identified as an important biomarker that maintains LUAD through The Cancer Genome Atlas (TCGA) project screening and confirmed by immunohistochemistry and qPCR. Via colony formation, CCK8, IncuCyte cell proliferation, wound healing and Transwell assays, we confirmed that PCBP1 was closely related to the proliferation and migration of LUAD cells. The downstream gene DKK1 was discovered by RNA sequencing of PCBP1 knockdown cells. The underlying mechanisms were further investigated using western blot, qPCR, RIP, RNA pulldown and mRNA stability assays. Results We demonstrate that PCBP1 is downregulated in LUAD tumour tissues. The reduction in PCBP1 promotes the proliferation, migration and invasion of LUAD in vitro and in vivo. Mechanistically, the RNA-binding protein PCBP1 represses LUAD by stabilizing DKK1 mRNA. Subsequently, decreased expression of the DKK1 protein relieves the inhibitory effect on the Wnt/β-catenin signalling pathway. Taken together, these results show that PCBP1 acts as a tumour suppressor gene, inhibiting the tumorigenesis of LUAD. Conclusions We found that PCBP1 inhibits LUAD development by upregulating DKK1 to inactivate the Wnt/β-catenin pathway. Our findings highlight the potential of PCBP1 as a promising therapeutic target.https://doi.org/10.1186/s12967-022-03552-yPCBP1DKK1LUADWnt signalling pathway |
| spellingShingle | Yujia Zheng Zheng Zhou Ran Wei Chu Xiao Hao Zhang Tao Fan Bo Zheng Chunxiang Li Jie He The RNA-binding protein PCBP1 represses lung adenocarcinoma progression by stabilizing DKK1 mRNA and subsequently downregulating β-catenin Journal of Translational Medicine PCBP1 DKK1 LUAD Wnt signalling pathway |
| title | The RNA-binding protein PCBP1 represses lung adenocarcinoma progression by stabilizing DKK1 mRNA and subsequently downregulating β-catenin |
| title_full | The RNA-binding protein PCBP1 represses lung adenocarcinoma progression by stabilizing DKK1 mRNA and subsequently downregulating β-catenin |
| title_fullStr | The RNA-binding protein PCBP1 represses lung adenocarcinoma progression by stabilizing DKK1 mRNA and subsequently downregulating β-catenin |
| title_full_unstemmed | The RNA-binding protein PCBP1 represses lung adenocarcinoma progression by stabilizing DKK1 mRNA and subsequently downregulating β-catenin |
| title_short | The RNA-binding protein PCBP1 represses lung adenocarcinoma progression by stabilizing DKK1 mRNA and subsequently downregulating β-catenin |
| title_sort | rna binding protein pcbp1 represses lung adenocarcinoma progression by stabilizing dkk1 mrna and subsequently downregulating β catenin |
| topic | PCBP1 DKK1 LUAD Wnt signalling pathway |
| url | https://doi.org/10.1186/s12967-022-03552-y |
| work_keys_str_mv | AT yujiazheng thernabindingproteinpcbp1represseslungadenocarcinomaprogressionbystabilizingdkk1mrnaandsubsequentlydownregulatingbcatenin AT zhengzhou thernabindingproteinpcbp1represseslungadenocarcinomaprogressionbystabilizingdkk1mrnaandsubsequentlydownregulatingbcatenin AT ranwei thernabindingproteinpcbp1represseslungadenocarcinomaprogressionbystabilizingdkk1mrnaandsubsequentlydownregulatingbcatenin AT chuxiao thernabindingproteinpcbp1represseslungadenocarcinomaprogressionbystabilizingdkk1mrnaandsubsequentlydownregulatingbcatenin AT haozhang thernabindingproteinpcbp1represseslungadenocarcinomaprogressionbystabilizingdkk1mrnaandsubsequentlydownregulatingbcatenin AT taofan thernabindingproteinpcbp1represseslungadenocarcinomaprogressionbystabilizingdkk1mrnaandsubsequentlydownregulatingbcatenin AT bozheng thernabindingproteinpcbp1represseslungadenocarcinomaprogressionbystabilizingdkk1mrnaandsubsequentlydownregulatingbcatenin AT chunxiangli thernabindingproteinpcbp1represseslungadenocarcinomaprogressionbystabilizingdkk1mrnaandsubsequentlydownregulatingbcatenin AT jiehe thernabindingproteinpcbp1represseslungadenocarcinomaprogressionbystabilizingdkk1mrnaandsubsequentlydownregulatingbcatenin AT yujiazheng rnabindingproteinpcbp1represseslungadenocarcinomaprogressionbystabilizingdkk1mrnaandsubsequentlydownregulatingbcatenin AT zhengzhou rnabindingproteinpcbp1represseslungadenocarcinomaprogressionbystabilizingdkk1mrnaandsubsequentlydownregulatingbcatenin AT ranwei rnabindingproteinpcbp1represseslungadenocarcinomaprogressionbystabilizingdkk1mrnaandsubsequentlydownregulatingbcatenin AT chuxiao rnabindingproteinpcbp1represseslungadenocarcinomaprogressionbystabilizingdkk1mrnaandsubsequentlydownregulatingbcatenin AT haozhang rnabindingproteinpcbp1represseslungadenocarcinomaprogressionbystabilizingdkk1mrnaandsubsequentlydownregulatingbcatenin AT taofan rnabindingproteinpcbp1represseslungadenocarcinomaprogressionbystabilizingdkk1mrnaandsubsequentlydownregulatingbcatenin AT bozheng rnabindingproteinpcbp1represseslungadenocarcinomaprogressionbystabilizingdkk1mrnaandsubsequentlydownregulatingbcatenin AT chunxiangli rnabindingproteinpcbp1represseslungadenocarcinomaprogressionbystabilizingdkk1mrnaandsubsequentlydownregulatingbcatenin AT jiehe rnabindingproteinpcbp1represseslungadenocarcinomaprogressionbystabilizingdkk1mrnaandsubsequentlydownregulatingbcatenin |