hnRNPM induces translation switch under hypoxia to promote colon cancer developmentResearch in Context
Background: Hypoxia suppresses global protein production, yet certain essential proteins are translated through alternative pathways to survive under hypoxic stress. Translation via the internal ribosome entry site (IRES) is a means to produce proteins under stress conditions such as hypoxia; howeve...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2019-03-01
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| Series: | EBioMedicine |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396419301380 |
| _version_ | 1819076510086070272 |
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| author | Tsung-Ming Chen Ming-Chih Lai Yi-Han Li Ya-Ling Chan Chih-Hao Wu Yu-Ming Wang Chun-Wei Chien San-Yuan Huang H. Sunny Sun Shaw-Jenq Tsai |
| author_facet | Tsung-Ming Chen Ming-Chih Lai Yi-Han Li Ya-Ling Chan Chih-Hao Wu Yu-Ming Wang Chun-Wei Chien San-Yuan Huang H. Sunny Sun Shaw-Jenq Tsai |
| author_sort | Tsung-Ming Chen |
| collection | DOAJ |
| description | Background: Hypoxia suppresses global protein production, yet certain essential proteins are translated through alternative pathways to survive under hypoxic stress. Translation via the internal ribosome entry site (IRES) is a means to produce proteins under stress conditions such as hypoxia; however, the underlying mechanism remains largely uncharacterized. Methods: Proteomic and bioinformatic analyses were employed to identify hnRNPM as an IRES interacting factor. Clinical specimens and mouse model of tumorigenesis were used for determining the expression and correlation of hnRNPM and its target gene. Transcriptomic and translatomic analyses were performed to profile target genes regulated by hnRNPM. Findings: Hypoxia increases cytosolic hnRNPM binding onto its target mRNAs and promotes translation initiation. Clinical colon cancer specimens and mouse carcinogenesis model showed that hnRNPM is elevated during the development of colorectal cancer, and is associated with poor prognosis. Genome-wide transcriptomics and translatomics analyses revealed a unique set of hnRNPM-targeted genes involved in metabolic processes and cancer neoplasia are selectively translated under hypoxia. Interpretation: These data highlight the critical role of hnRNPM-IRES-mediated translation in transforming hypoxia-induced proteome toward malignancy. Fund: This work was supported by the Ministry of Science and Technology, Taiwan (MOST 104–2320-B-006-042 to HSS and MOST 105–2628-B-001-MY3 to TMC). Keywords: Hypoxia, Colon cancer, IRES, Translational reprogramming, Translatomics, Tumorigenesis |
| first_indexed | 2024-12-21T18:42:27Z |
| format | Article |
| id | doaj.art-df755005ea654497a0a04b7f39cc6562 |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-12-21T18:42:27Z |
| publishDate | 2019-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-df755005ea654497a0a04b7f39cc65622022-12-21T18:53:58ZengElsevierEBioMedicine2352-39642019-03-0141299309hnRNPM induces translation switch under hypoxia to promote colon cancer developmentResearch in ContextTsung-Ming Chen0Ming-Chih Lai1Yi-Han Li2Ya-Ling Chan3Chih-Hao Wu4Yu-Ming Wang5Chun-Wei Chien6San-Yuan Huang7H. Sunny Sun8Shaw-Jenq Tsai9Department of Physiology, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department and Graduate Institute of Aquaculture, National Kaohsiung Marine University, Kaohsiung, TaiwanDepartment of Physiology, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Biomedical Sciences, Chang Gung University, Taoyuan, TaiwanInstitute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, TaiwanInstitute of Bioinformatics and Biosignaling, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, TaiwanInstitute of Molecular Medicine, College of Medicine, National Cheng Kung University, Tainan, TaiwanInstitute of Molecular Medicine, College of Medicine, National Cheng Kung University, Tainan, TaiwanDepartment of Physiology, College of Medicine, National Cheng Kung University, Tainan, TaiwanDepartment of Animal Science, National Chung Hsing University, Taichung, TaiwanInstitute of Molecular Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Corresponding authors.Department of Physiology, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Corresponding authors.Background: Hypoxia suppresses global protein production, yet certain essential proteins are translated through alternative pathways to survive under hypoxic stress. Translation via the internal ribosome entry site (IRES) is a means to produce proteins under stress conditions such as hypoxia; however, the underlying mechanism remains largely uncharacterized. Methods: Proteomic and bioinformatic analyses were employed to identify hnRNPM as an IRES interacting factor. Clinical specimens and mouse model of tumorigenesis were used for determining the expression and correlation of hnRNPM and its target gene. Transcriptomic and translatomic analyses were performed to profile target genes regulated by hnRNPM. Findings: Hypoxia increases cytosolic hnRNPM binding onto its target mRNAs and promotes translation initiation. Clinical colon cancer specimens and mouse carcinogenesis model showed that hnRNPM is elevated during the development of colorectal cancer, and is associated with poor prognosis. Genome-wide transcriptomics and translatomics analyses revealed a unique set of hnRNPM-targeted genes involved in metabolic processes and cancer neoplasia are selectively translated under hypoxia. Interpretation: These data highlight the critical role of hnRNPM-IRES-mediated translation in transforming hypoxia-induced proteome toward malignancy. Fund: This work was supported by the Ministry of Science and Technology, Taiwan (MOST 104–2320-B-006-042 to HSS and MOST 105–2628-B-001-MY3 to TMC). Keywords: Hypoxia, Colon cancer, IRES, Translational reprogramming, Translatomics, Tumorigenesishttp://www.sciencedirect.com/science/article/pii/S2352396419301380 |
| spellingShingle | Tsung-Ming Chen Ming-Chih Lai Yi-Han Li Ya-Ling Chan Chih-Hao Wu Yu-Ming Wang Chun-Wei Chien San-Yuan Huang H. Sunny Sun Shaw-Jenq Tsai hnRNPM induces translation switch under hypoxia to promote colon cancer developmentResearch in Context EBioMedicine |
| title | hnRNPM induces translation switch under hypoxia to promote colon cancer developmentResearch in Context |
| title_full | hnRNPM induces translation switch under hypoxia to promote colon cancer developmentResearch in Context |
| title_fullStr | hnRNPM induces translation switch under hypoxia to promote colon cancer developmentResearch in Context |
| title_full_unstemmed | hnRNPM induces translation switch under hypoxia to promote colon cancer developmentResearch in Context |
| title_short | hnRNPM induces translation switch under hypoxia to promote colon cancer developmentResearch in Context |
| title_sort | hnrnpm induces translation switch under hypoxia to promote colon cancer developmentresearch in context |
| url | http://www.sciencedirect.com/science/article/pii/S2352396419301380 |
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