Heterogenous ribonucleoprotein A18 (hnRNP A18) promotes tumor growth by increasing protein translation of selected transcripts in cancer cells

The heterogenous ribonucleoprotein A18 (hnRNP A18) promotes tumor growth by coordinating the translation of selected transcripts associated with proliferation and survival. hnRNP A18 binds to and stabilizes the transcripts of pro-survival genes harboring its RNA signature motif in their 3′UTRs. hnRNP A18 binds to ATR, RPA, TRX, HIF-1α and several protein translation factor mRNAs on polysomes and increases de novo protein translation under cellular stress. Most importantly, down regulation of hnRNP A18 decreases proliferation, invasion and migration in addition to significantly reducing tumor growth in two mouse xenograft models, melanoma and breast cancer. Moreover, tissue microarrays performed on human melanoma, prostate, breast and colon cancer indicate that hnRNP A18 is over expressed in 40 to 60% of these malignant tissue as compared to normal adjacent tissue. Immunohistochemistry data indicate that hnRNP A18 is over expressed in the stroma and hypoxic areas of human tumors. These data thus indicate that hnRNP A18 can promote tumor growth in in vivo models by coordinating the translation of pro-survival transcripts to support the demands of proliferating cells and increase survival under cellular stress. hnRNP A18 therefore represents a new target to selectively inhibit protein translation in tumor cells.

• Publication year

  2016

• Venue

  OncoTarget

• Publication date

  2016-01-25

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.18632/oncotarget.7020PMID 26824423PMCID 4891142
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Stress response protein cirp links inflammation and tumorigenesis in colitis-associated cancer.

  2014cited by this paper
• Cold-inducible RNA-binding protein (CIRP) triggers inflammatory responses in hemorrhagic shock and sepsis

  2013cited by this paper
• hnRNP A18: A New Pathway to Regulate Protein Translation in Cancer Cells

  2012cited by this paper
• HuR function in disease.

  2012cited by this paper
• Regulation of mammalian target of rapamycin complex 1 (mTORC1) by hypoxia: causes and consequences

  2011cited by this paper
• Functional Significance for a Heterogenous Ribonucleoprotein A18 Signature RNA Motif in the 3′-Untranslated Region of Ataxia Telangiectasia Mutated and Rad3-related (ATR) Transcript*

  2010influential reference
• A new generation of proto-oncogenes: cold-inducible RNA binding proteins.

  2010cited by this paper
• ATR-Chk1 pathway inhibition promotes apoptosis after UV treatment in primary human keratinocytes: potential basis for the UV protective effects of caffeine.

  2009cited by this paper
• Expression and function of hypoxia inducible factor-1 alpha in human melanoma under non-hypoxic conditions

  2009cited by this paper
• Cold-inducible RNA binding protein (CIRP) expression is modulated by alternative mRNAs.

  2009cited by this paper
• HIF-1α determines the metastatic potential of gastric cancer cells

  2009cited by this paper
• Cold-Inducible RNA-Binding Protein Bypasses Replicative Senescence in Primary Cells through Extracellular Signal-Regulated Kinase 1 and 2 Activation

  2009influential reference
• Cycling hypoxia and free radicals regulate angiogenesis and radiotherapy response

  2008cited by this paper
• Cycling hypoxia and free radicals regulate angiogenesis and radiotherapy response

  2008cited by this paper
• Increased expression of thioredoxin-1, vascular endothelial growth factor, and redox factor-1 is associated with poor prognosis in patients with liver metastasis from colorectal cancer.

  2008cited by this paper
• RNA regulons: coordination of post-transcriptional events

  2007cited by this paper
• Hypoxia Inhibits Protein Synthesis through a 4E-BP1 and Elongation Factor 2 Kinase Pathway Controlled by mTOR and Uncoupled in Breast Cancer Cells

  2006cited by this paper
• Post-transcriptional regulation of thioredoxin by the stress inducible heterogenous ribonucleoprotein A18

  2006influential reference
• Oxygen-regulated expression of the RNA-binding proteins RBM3 and CIRP by a HIF-1-independent mechanism

  2004influential reference
• Ribonomics: identifying mRNA subsets in mRNP complexes using antibodies to RNA-binding proteins and genomic arrays.

  2002cited by this paper
• Hypoxia — a key regulatory factor in tumour growth

  2002cited by this paper
• The UV-inducible RNA-binding Protein A18 (A18 hnRNP) Plays a Protective Role in the Genotoxic Stress Response*

  2001influential reference
• Coordinate up-regulation of hypoxia inducible factor (HIF)-1alpha and HIF-1 target genes during multi-stage epidermal carcinogenesis and wound healing.

  2000cited by this paper
• Identification of Several Human Homologs of Hamster DNA Damage-inducible Transcripts

  1997cited by this paper
• Cloning and characterization of human CIRP (cold-inducible RNA-binding protein) cDNA and chromosomal assignment of the gene.

  1997cited by this paper
• DNA damage-inducible transcripts in mammalian cells.

  1988cited by this paper

• An overview of vital functions of human ecdysoneless (ECD), a highly conserved protein

  2025cites this paper
• Correction to ‘Small molecules inhibitors of the heterogeneous ribonuclear protein A18 (hnRNP A18): a regulator of protein translation and an immune checkpoint’

  2025cites this paper
• Cold-inducible RNA-binding protein is associated with subtype-specific breast cancer patient outcomes

  2025cites this paper
• Cold-Inducible RNA Binding Protein Impedes Breast Tumor Growth in the PyMT Murine Model for Breast Cancer

  2024cites this paper
• Challenges in Therapeutically Targeting the RNA‐Recognition Motif

  2024cites this paper
• Inhibition of CIRBP represses the proliferation and migration of vascular smooth muscle cells via inhibiting Rheb/mTORC1 axis.

  2024cites this paper
• 1H, 13C, and 15N assignments of the mRNA binding protein hnRNP A18

  2022cites this paper
• The long non-coding RNA MEG8 induces an endothelial barrier through regulation of microRNA-370 and -494 processing

  2022cites this paper
• Small molecules inhibitors of the heterogeneous ribonuclear protein A18 (hnRNP A18): a regulator of protein translation and an immune checkpoint

  2021cites this paper
• Invasive growth associated with Cold-Inducible RNA-Binding Protein expression drives recurrence of surgically resected brain metastases.

  2021cites this paper
• Alternative polyadenylation: methods, mechanism, function, and role in cancer

  2021cites this paper
• The Role of Cold Inducible RNA-Binding Protein in Cardiac Physiology and Diseases

  2021cites this paper
• Absence of Cold-Inducible RNA-Binding Protein (CIRP) Promotes Angiogenesis and Regeneration of Ischemic Tissue by Inducing M2-Like Macrophage Polarization

  2021cites this paper
• Systematic analysis of the function and prognostic value of RNA binding protein in head and neck squamous cell carcinoma

  2021cites this paper
• Controversial roles of cold‑inducible RNA‑binding protein in human cancer (Review).

  2021cites this paper
• Aging Induces Hepatic Oxidative Stress and Nuclear Proteomic Remodeling in Liver from Wistar Rats

  2021cites this paper
• The role of Cold‐Inducible RNA‐binding protein in respiratory diseases

  2021cites this paper
• Systematic Analysis of the Functions and Prognostic Values of Rna Binding Protein in Head and Neck Squamous Cell Carcinoma

  2020cites this paper
• Cold-inducible RNA binding protein promotes breast cancer cell malignancy by regulating Cystatin C levels

  2020influential citation
• Post-transcriptional regulation of miRNA biogenesis

  2019cites this paper
• Association between CIRP expression and hypoxic-ischemic brain injury in neonatal rats

  2019cites this paper
• Post-transcriptional Regulation of Colorectal Cancer: A Focus on RNA-Binding Proteins

  2019cites this paper
• Loss of Cirbp expression is correlated with the malignant progression and poor prognosis in nasopharyngeal carcinoma

  2019cites this paper
• CIRBP is a novel oncogene in human bladder cancer inducing expression of HIF-1α

  2018cites this paper
• Cold‐inducible RNA binding protein in cancer and inflammation

  2018cites this paper
• The Mechanism of CIRP in Regulation of STAT3 Phosphorylation and Bag‐1/S Expression Upon UVB Radiation

  2018cites this paper
• PARP-1–dependent recruitment of cold-inducible RNA-binding protein promotes double-strand break repair and genome stability

  2018cites this paper
• ECD promotes gastric cancer metastasis by blocking E3 ligase ZFP91-mediated hnRNP F ubiquitination and degradation

  2018cites this paper
• Cold-inducible RNA-binding protein (CIRP) induces translation of the cell-cycle inhibitor p27Kip1

  2018cites this paper
• DNA damage response and repair in colorectal cancer: Defects, regulation and therapeutic implications.

  2018cites this paper
• Recent progress in the research of cold-inducible RNA-binding protein

  2017cites this paper
• Crystal structure of the human heterogeneous ribonucleoprotein A18 RNA-recognition motif.

  2017influential citation
• Cold Inducible RNA Binding Protein Is Involved in Chronic Hypoxia Induced Neuron Apoptosis by Down-Regulating HIF-1α Expression and Regulated By microRNA-23a

  2017cites this paper
• RNA-Binding Protein Dnd1 Promotes Breast Cancer Apoptosis by Stabilizing the Bim mRNA in a miR-221 Binding Site

  2017cites this paper
• CIRP may be a New Potential Target in Prostate Cancer

  2017cites this paper
• Long Noncoding RNAs and RNA-Binding Proteins in Oxidative Stress, Cellular Senescence, and Age-Related Diseases

  2017influential citation
• World Journal of Gastrointestinal Oncology

  year unknowncites this paper