PTBP1 promotes hepatocellular carcinoma progression by regulating the skipping of exon 9 in NUMB pre-mRNA
Aberrant alternative splicing is one of the important causes of cancer. Polypyrimidine tract binding protein 1 (PTBP1) has been found to be involved in splicing regulation in a variety of tumors. Here, we observed significant up-regulation of PTBP1 in primary hepatocellular carcinoma (HCC) tissues....
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-06-01
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| Series: | Heliyon |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844023045954 |
| _version_ | 1797794612078706688 |
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| author | Zhentao He Qianhua Ni Xichun Li Mingyu Zhao Qingguo Mo Yongsheng Duo |
| author_facet | Zhentao He Qianhua Ni Xichun Li Mingyu Zhao Qingguo Mo Yongsheng Duo |
| author_sort | Zhentao He |
| collection | DOAJ |
| description | Aberrant alternative splicing is one of the important causes of cancer. Polypyrimidine tract binding protein 1 (PTBP1) has been found to be involved in splicing regulation in a variety of tumors. Here, we observed significant up-regulation of PTBP1 in primary hepatocellular carcinoma (HCC) tissues. High levels of PTBP1 expression were associated with poor prognosis and increased metastatic potential in HCC. In vitro studies demonstrated that elevated PTBP1 promoted both migration and invasion by HCC cells. In contrast, knockdown of PTBP1 significantly inhibited the migration and invasion of HCC cells in vitro. Further, up-regulation of PTBP1 markedly accumulated the expression of oncogenic isoform of NUMB, NUMB-PRRL. We observed two isoforms of NUMB, NUMB-PRRL and NUMB-PRRS exhibit opposite function in HCC cells, which partially explain PTBP1 plays the tumor promoting roles in a NUMB splicing-dependent manner. In summary, our study indicates that PTBP1 may serve as an oncogene in HCC patients by regulating the alternative splicing of NUMB exon 9 and could potentially serve as a prognostic indicator. |
| first_indexed | 2024-03-13T03:05:27Z |
| format | Article |
| id | doaj.art-21166d3199e2453490dae30f7f1b08e7 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-03-13T03:05:27Z |
| publishDate | 2023-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-21166d3199e2453490dae30f7f1b08e72023-06-27T04:04:09ZengElsevierHeliyon2405-84402023-06-0196e17387PTBP1 promotes hepatocellular carcinoma progression by regulating the skipping of exon 9 in NUMB pre-mRNAZhentao He0Qianhua Ni1Xichun Li2Mingyu Zhao3Qingguo Mo4Yongsheng Duo5The Third Affiliated Hospital of Qiqihar Medical College, Qiqihar 161099, ChinaThe Third Affiliated Hospital of Qiqihar Medical College, Qiqihar 161099, ChinaThe Third Affiliated Hospital of Qiqihar Medical College, Qiqihar 161099, ChinaThe Third Affiliated Hospital of Qiqihar Medical College, Qiqihar 161099, ChinaThe Third Affiliated Hospital of Qiqihar Medical College, Qiqihar 161099, ChinaCorresponding author.; The Third Affiliated Hospital of Qiqihar Medical College, Qiqihar 161099, ChinaAberrant alternative splicing is one of the important causes of cancer. Polypyrimidine tract binding protein 1 (PTBP1) has been found to be involved in splicing regulation in a variety of tumors. Here, we observed significant up-regulation of PTBP1 in primary hepatocellular carcinoma (HCC) tissues. High levels of PTBP1 expression were associated with poor prognosis and increased metastatic potential in HCC. In vitro studies demonstrated that elevated PTBP1 promoted both migration and invasion by HCC cells. In contrast, knockdown of PTBP1 significantly inhibited the migration and invasion of HCC cells in vitro. Further, up-regulation of PTBP1 markedly accumulated the expression of oncogenic isoform of NUMB, NUMB-PRRL. We observed two isoforms of NUMB, NUMB-PRRL and NUMB-PRRS exhibit opposite function in HCC cells, which partially explain PTBP1 plays the tumor promoting roles in a NUMB splicing-dependent manner. In summary, our study indicates that PTBP1 may serve as an oncogene in HCC patients by regulating the alternative splicing of NUMB exon 9 and could potentially serve as a prognostic indicator.http://www.sciencedirect.com/science/article/pii/S2405844023045954Hepatocellular carcinomaAlternative splicingPTBP1NUMB |
| spellingShingle | Zhentao He Qianhua Ni Xichun Li Mingyu Zhao Qingguo Mo Yongsheng Duo PTBP1 promotes hepatocellular carcinoma progression by regulating the skipping of exon 9 in NUMB pre-mRNA Heliyon Hepatocellular carcinoma Alternative splicing PTBP1 NUMB |
| title | PTBP1 promotes hepatocellular carcinoma progression by regulating the skipping of exon 9 in NUMB pre-mRNA |
| title_full | PTBP1 promotes hepatocellular carcinoma progression by regulating the skipping of exon 9 in NUMB pre-mRNA |
| title_fullStr | PTBP1 promotes hepatocellular carcinoma progression by regulating the skipping of exon 9 in NUMB pre-mRNA |
| title_full_unstemmed | PTBP1 promotes hepatocellular carcinoma progression by regulating the skipping of exon 9 in NUMB pre-mRNA |
| title_short | PTBP1 promotes hepatocellular carcinoma progression by regulating the skipping of exon 9 in NUMB pre-mRNA |
| title_sort | ptbp1 promotes hepatocellular carcinoma progression by regulating the skipping of exon 9 in numb pre mrna |
| topic | Hepatocellular carcinoma Alternative splicing PTBP1 NUMB |
| url | http://www.sciencedirect.com/science/article/pii/S2405844023045954 |
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