[HTML][HTML] hnRNPM induces translation switch under hypoxia to promote colon cancer development
TM Chen, MC Lai, YH Li, YL Chan, CH Wu… - …, 2019 - thelancet.com
EBioMedicine, 2019•thelancet.com
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 …
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 …
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).
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