hnRNPM induces translation switch under hypoxia to promote colon cancer development

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

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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).

Original languageEnglish
Pages (from-to)299-309
Number of pages11
JournalEBioMedicine
Volume41
DOIs
Publication statusPublished - 2019 Mar

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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    Chen, T. M., Lai, M. C., Li, Y. H., Chan, Y. L., Wu, C. H., Wang, Y. M., Chien, C. W., Huang, S. Y., Sun, H. S., & Tsai, S. J. (2019). hnRNPM induces translation switch under hypoxia to promote colon cancer development. EBioMedicine, 41, 299-309. https://doi.org/10.1016/j.ebiom.2019.02.059