Downregulation of hnRNPA1 inhibits hepatocellular carcinoma cell progression by modulating alternative splicing of ZNF207 exon 9
IntroductionHepatocellular carcinoma (HCC) is the most prevalent liver cancer and a leading cause of cancer-related deaths worldwide. Heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) plays a critical role in RNA metabolism, including alternative splicing, which is linked to cancer progression. O...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-01-01
|
| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2024.1517459/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841558632457568256 |
|---|---|
| author | Qi Ouyang Qi Ouyang Wenhui He Yiping Guo Lin Li Ying Mao Xiang Li Shuanglin Xiang Xiang Hu Jun He |
| author_facet | Qi Ouyang Qi Ouyang Wenhui He Yiping Guo Lin Li Ying Mao Xiang Li Shuanglin Xiang Xiang Hu Jun He |
| author_sort | Qi Ouyang |
| collection | DOAJ |
| description | IntroductionHepatocellular carcinoma (HCC) is the most prevalent liver cancer and a leading cause of cancer-related deaths worldwide. Heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) plays a critical role in RNA metabolism, including alternative splicing, which is linked to cancer progression. Our study investigated the role of hnRNPA1 in HCC and its potential as a therapeutic target.MethodsWe analyzed hnRNPA1 expression in HCC tissues compared to non-tumor tissues using RNA-seq and immunohistochemistry. hnRNPA1 was knocked down in Hep G2 cells to assess its impact on cell proliferation, migration, and apoptosis using scratch assays, flow cytometry, qPCR, and Western blot. We also explored the interaction between hnRNPA1 and ZNF207, as well as its splicing effects and downstream signaling pathways by RIP assay, bioinformatics, qPCR and Western blot.ResultshnRNPA1 was significantly upregulated in HCC tissues compared to normal tissues, correlating with poor patient survival. hnRNPA1 knockdown reduced Hep G2 cell proliferation and migration while increasing apoptosis. We identified that hnRNPA1 bound to ZNF207 and regulated its exon 9 skipping, influencing ZNF207 splicing and the PI3K/Akt/mTOR pathway, key regulators of cell growth and survival.ConclusionOur findings demonstrate that hnRNPA1 promotes HCC progression by regulating ZNF207 splicing and the PI3K/Akt/mTOR pathway. hnRNPA1-ZNF207 interaction represents a potential therapeutic target for HCC, providing insights into the molecular mechanisms underlying HCC progression. |
| format | Article |
| id | doaj-art-4a23d0a7242345d889606067267fa98c |
| institution | Kabale University |
| issn | 2234-943X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj-art-4a23d0a7242345d889606067267fa98c2025-01-06T06:59:41ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-01-011410.3389/fonc.2024.15174591517459Downregulation of hnRNPA1 inhibits hepatocellular carcinoma cell progression by modulating alternative splicing of ZNF207 exon 9Qi Ouyang0Qi Ouyang1Wenhui He2Yiping Guo3Lin Li4Ying Mao5Xiang Li6Shuanglin Xiang7Xiang Hu8Jun He9Hunan Provincial Key Laboratory of Regional Hereditary Birth Defects Prevention and Control, Changsha Hospital for Maternal & Child Health Care Affiliated to Hunan Normal University, Hunan Normal University, Changsha, ChinaState Key Laboratory of Developmental Biology of Freshwater Fish, College of Life Sciences, Hunan Normal University, Changsha, ChinaState Key Laboratory of Developmental Biology of Freshwater Fish, College of Life Sciences, Hunan Normal University, Changsha, ChinaState Key Laboratory of Developmental Biology of Freshwater Fish, College of Life Sciences, Hunan Normal University, Changsha, ChinaState Key Laboratory of Developmental Biology of Freshwater Fish, College of Life Sciences, Hunan Normal University, Changsha, ChinaState Key Laboratory of Developmental Biology of Freshwater Fish, College of Life Sciences, Hunan Normal University, Changsha, ChinaHunan Provincial Key Laboratory of Regional Hereditary Birth Defects Prevention and Control, Changsha Hospital for Maternal & Child Health Care Affiliated to Hunan Normal University, Hunan Normal University, Changsha, ChinaState Key Laboratory of Developmental Biology of Freshwater Fish, College of Life Sciences, Hunan Normal University, Changsha, ChinaState Key Laboratory of Developmental Biology of Freshwater Fish, College of Life Sciences, Hunan Normal University, Changsha, ChinaHunan Provincial Key Laboratory of Regional Hereditary Birth Defects Prevention and Control, Changsha Hospital for Maternal & Child Health Care Affiliated to Hunan Normal University, Hunan Normal University, Changsha, ChinaIntroductionHepatocellular carcinoma (HCC) is the most prevalent liver cancer and a leading cause of cancer-related deaths worldwide. Heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) plays a critical role in RNA metabolism, including alternative splicing, which is linked to cancer progression. Our study investigated the role of hnRNPA1 in HCC and its potential as a therapeutic target.MethodsWe analyzed hnRNPA1 expression in HCC tissues compared to non-tumor tissues using RNA-seq and immunohistochemistry. hnRNPA1 was knocked down in Hep G2 cells to assess its impact on cell proliferation, migration, and apoptosis using scratch assays, flow cytometry, qPCR, and Western blot. We also explored the interaction between hnRNPA1 and ZNF207, as well as its splicing effects and downstream signaling pathways by RIP assay, bioinformatics, qPCR and Western blot.ResultshnRNPA1 was significantly upregulated in HCC tissues compared to normal tissues, correlating with poor patient survival. hnRNPA1 knockdown reduced Hep G2 cell proliferation and migration while increasing apoptosis. We identified that hnRNPA1 bound to ZNF207 and regulated its exon 9 skipping, influencing ZNF207 splicing and the PI3K/Akt/mTOR pathway, key regulators of cell growth and survival.ConclusionOur findings demonstrate that hnRNPA1 promotes HCC progression by regulating ZNF207 splicing and the PI3K/Akt/mTOR pathway. hnRNPA1-ZNF207 interaction represents a potential therapeutic target for HCC, providing insights into the molecular mechanisms underlying HCC progression.https://www.frontiersin.org/articles/10.3389/fonc.2024.1517459/fullliver cancerzinc finger protein 207alternative splicegene regulationPI3K/AKT/mTOR |
| spellingShingle | Qi Ouyang Qi Ouyang Wenhui He Yiping Guo Lin Li Ying Mao Xiang Li Shuanglin Xiang Xiang Hu Jun He Downregulation of hnRNPA1 inhibits hepatocellular carcinoma cell progression by modulating alternative splicing of ZNF207 exon 9 Frontiers in Oncology liver cancer zinc finger protein 207 alternative splice gene regulation PI3K/AKT/mTOR |
| title | Downregulation of hnRNPA1 inhibits hepatocellular carcinoma cell progression by modulating alternative splicing of ZNF207 exon 9 |
| title_full | Downregulation of hnRNPA1 inhibits hepatocellular carcinoma cell progression by modulating alternative splicing of ZNF207 exon 9 |
| title_fullStr | Downregulation of hnRNPA1 inhibits hepatocellular carcinoma cell progression by modulating alternative splicing of ZNF207 exon 9 |
| title_full_unstemmed | Downregulation of hnRNPA1 inhibits hepatocellular carcinoma cell progression by modulating alternative splicing of ZNF207 exon 9 |
| title_short | Downregulation of hnRNPA1 inhibits hepatocellular carcinoma cell progression by modulating alternative splicing of ZNF207 exon 9 |
| title_sort | downregulation of hnrnpa1 inhibits hepatocellular carcinoma cell progression by modulating alternative splicing of znf207 exon 9 |
| topic | liver cancer zinc finger protein 207 alternative splice gene regulation PI3K/AKT/mTOR |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2024.1517459/full |
| work_keys_str_mv | AT qiouyang downregulationofhnrnpa1inhibitshepatocellularcarcinomacellprogressionbymodulatingalternativesplicingofznf207exon9 AT qiouyang downregulationofhnrnpa1inhibitshepatocellularcarcinomacellprogressionbymodulatingalternativesplicingofznf207exon9 AT wenhuihe downregulationofhnrnpa1inhibitshepatocellularcarcinomacellprogressionbymodulatingalternativesplicingofznf207exon9 AT yipingguo downregulationofhnrnpa1inhibitshepatocellularcarcinomacellprogressionbymodulatingalternativesplicingofznf207exon9 AT linli downregulationofhnrnpa1inhibitshepatocellularcarcinomacellprogressionbymodulatingalternativesplicingofznf207exon9 AT yingmao downregulationofhnrnpa1inhibitshepatocellularcarcinomacellprogressionbymodulatingalternativesplicingofznf207exon9 AT xiangli downregulationofhnrnpa1inhibitshepatocellularcarcinomacellprogressionbymodulatingalternativesplicingofznf207exon9 AT shuanglinxiang downregulationofhnrnpa1inhibitshepatocellularcarcinomacellprogressionbymodulatingalternativesplicingofznf207exon9 AT xianghu downregulationofhnrnpa1inhibitshepatocellularcarcinomacellprogressionbymodulatingalternativesplicingofznf207exon9 AT junhe downregulationofhnrnpa1inhibitshepatocellularcarcinomacellprogressionbymodulatingalternativesplicingofznf207exon9 |