Requirement of splicing factor hnRNP A2B1 for tumorigenesis of melanoma stem cells
Abstract Background Cancer stem cells play essential roles in tumorigenesis, thus forming an important target for tumor therapy. The hnRNP family proteins are important splicing factors that have been found to be associated with tumor progression. However, the influence of hnRNPs on cancer stem cell...
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| Format: | Article |
| Language: | English |
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BMC
2021-01-01
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| Series: | Stem Cell Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13287-020-02124-5 |
| _version_ | 1828926068496531456 |
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| author | Mengqi Chu Haitao Wan Xiaobo Zhang |
| author_facet | Mengqi Chu Haitao Wan Xiaobo Zhang |
| author_sort | Mengqi Chu |
| collection | DOAJ |
| description | Abstract Background Cancer stem cells play essential roles in tumorigenesis, thus forming an important target for tumor therapy. The hnRNP family proteins are important splicing factors that have been found to be associated with tumor progression. However, the influence of hnRNPs on cancer stem cells has not been extensively explored. Methods Quantitative real-time PCR and Western blot were used to examine gene expressions. RNA immunoprecipitation assays were conducted to identify the RNAs interacted with hnRNP A2B1. The in vivo assays were performed in nude mice. Results In this study, the results showed that out of 19 evaluated hnRNPs, hnRNP A2B1 was significantly upregulated in melanoma stem cells compared with non-stem cells, suggesting an important role of hnRNP A2B1 in cancer stem cells. Silencing of hnRNP A2B1 triggered cell cycle arrest in G2 phase, leading to apoptosis of melanoma stem cells. The results also revealed that hnRNP A2B1 could bind to the precursor mRNAs of pro-apoptosis genes (DAPK1, SYT7, and RNF128) and anti-apoptosis genes (EIF3H, TPPP3, and DOCK2) to regulate the splicing of these 6 genes, thus promoting the expressions of anti-apoptosis genes and suppressing the expressions of pro-apoptosis genes. The in vivo data indicated that hnRNP A2B1 was required for tumorigenesis by affecting the splicing of TPPP3, DOCK2, EIF3H, RNF128, DAPK1, and SYT7, thus suppressing apoptosis of melanoma stem cells. Conclusion Our findings showed the requirement of hnRNP A2B1 for tumorigenesis, thus presenting novel molecular insights into the role of hnRNPs in cancer stem cells. |
| first_indexed | 2024-12-13T23:26:11Z |
| format | Article |
| id | doaj.art-661455cdb9c949c6976a4143d0699187 |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-12-13T23:26:11Z |
| publishDate | 2021-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-661455cdb9c949c6976a4143d06991872022-12-21T23:27:33ZengBMCStem Cell Research & Therapy1757-65122021-01-0112111510.1186/s13287-020-02124-5Requirement of splicing factor hnRNP A2B1 for tumorigenesis of melanoma stem cellsMengqi Chu0Haitao Wan1Xiaobo Zhang2College of Life Sciences and Laboratory for Marine Biology and Biotechnology of Pilot National Laboratory for Marine Science and Technology (Qingdao), Zhejiang UniversityCollege of Life Sciences and Laboratory for Marine Biology and Biotechnology of Pilot National Laboratory for Marine Science and Technology (Qingdao), Zhejiang UniversityCollege of Life Sciences and Laboratory for Marine Biology and Biotechnology of Pilot National Laboratory for Marine Science and Technology (Qingdao), Zhejiang UniversityAbstract Background Cancer stem cells play essential roles in tumorigenesis, thus forming an important target for tumor therapy. The hnRNP family proteins are important splicing factors that have been found to be associated with tumor progression. However, the influence of hnRNPs on cancer stem cells has not been extensively explored. Methods Quantitative real-time PCR and Western blot were used to examine gene expressions. RNA immunoprecipitation assays were conducted to identify the RNAs interacted with hnRNP A2B1. The in vivo assays were performed in nude mice. Results In this study, the results showed that out of 19 evaluated hnRNPs, hnRNP A2B1 was significantly upregulated in melanoma stem cells compared with non-stem cells, suggesting an important role of hnRNP A2B1 in cancer stem cells. Silencing of hnRNP A2B1 triggered cell cycle arrest in G2 phase, leading to apoptosis of melanoma stem cells. The results also revealed that hnRNP A2B1 could bind to the precursor mRNAs of pro-apoptosis genes (DAPK1, SYT7, and RNF128) and anti-apoptosis genes (EIF3H, TPPP3, and DOCK2) to regulate the splicing of these 6 genes, thus promoting the expressions of anti-apoptosis genes and suppressing the expressions of pro-apoptosis genes. The in vivo data indicated that hnRNP A2B1 was required for tumorigenesis by affecting the splicing of TPPP3, DOCK2, EIF3H, RNF128, DAPK1, and SYT7, thus suppressing apoptosis of melanoma stem cells. Conclusion Our findings showed the requirement of hnRNP A2B1 for tumorigenesis, thus presenting novel molecular insights into the role of hnRNPs in cancer stem cells.https://doi.org/10.1186/s13287-020-02124-5MelanomaCancer stem cellshnRNPApoptosisTumorigenesis |
| spellingShingle | Mengqi Chu Haitao Wan Xiaobo Zhang Requirement of splicing factor hnRNP A2B1 for tumorigenesis of melanoma stem cells Stem Cell Research & Therapy Melanoma Cancer stem cells hnRNP Apoptosis Tumorigenesis |
| title | Requirement of splicing factor hnRNP A2B1 for tumorigenesis of melanoma stem cells |
| title_full | Requirement of splicing factor hnRNP A2B1 for tumorigenesis of melanoma stem cells |
| title_fullStr | Requirement of splicing factor hnRNP A2B1 for tumorigenesis of melanoma stem cells |
| title_full_unstemmed | Requirement of splicing factor hnRNP A2B1 for tumorigenesis of melanoma stem cells |
| title_short | Requirement of splicing factor hnRNP A2B1 for tumorigenesis of melanoma stem cells |
| title_sort | requirement of splicing factor hnrnp a2b1 for tumorigenesis of melanoma stem cells |
| topic | Melanoma Cancer stem cells hnRNP Apoptosis Tumorigenesis |
| url | https://doi.org/10.1186/s13287-020-02124-5 |
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