CIRBP

Official Full Name

cold inducible RNA binding protein

Organism

Homo sapiens

GeneID

1153

Background

Enables mRNA 3'-UTR binding activity and small ribosomal subunit rRNA binding activity. Involved in mRNA stabilization; positive regulation of translation; and response to UV. Located in cytoplasm and nucleoplasm. [provided by Alliance of Genome Resources, Feb 2025]

Synonyms

CIRP;

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Detailed Information

Recent Research Progress

Cold-inducible RNA-binding protein (CIRBP), also known as CIRP or A18 hnRNP, is an 18kDa cold shock protein that is a member of the glycine-rich RNA-binding protein family, and was originally found in mammalian cells. As a multifunctional protein, CIRBP plays a vital role in many biological activities, such as tumorigenesis, hypothermic injury, ultraviolet radiation-related inflammation, clock gene regulation and limb regeneration. Furthermore, there is increasing evidence that CIRBP is a pro-inflammatory cytokine that induces various inflammatory responses.

CIRBP and OSCC

Oral squamous cell carcinoma (OSCC) is the most common malignant tumor of the head and neck. Recent studies have confirmed that CIRBP expression is increased in OSCC, and high expression levels of CIRBP or toll-like receptors 4 (TLR4) are associated with shorter survival rates. Moreover, the study found that the expression levels of CIRBP and TLR4 are very similar. In conclusion, expression of CIRBP and TLR4 is increased in OSCC and plays an important role in long-term prognosis. Identification of these two genes can provide clues about the regulatory mechanisms of OSCC and suggest that their up-regulation in OSCC etiology can also serve as a prognostic marker.

CIRBP and HCC

Most hepatocellular carcinoma (HCC) develops in the context of chronic liver inflammation. Oxidative stress is thought to play a major role in the pathogenesis of HCC development. Sakura et al examined whether CIRBP controls the accumulation and development of reactive oxygen species (ROS) in HCC by using a mouse model of hepatocarcinogenesis and human liver samples. CIRBP expression, ROS accumulation and CD133 expression were increased in the liver of tumor-harboring mice. CIRBP deficiency reduced the production of interleukin-1b and interleukin-6 in Kupffer cells, ROS accumulation and CD133 expression, resulting in reduced hepatocarcinogenesis. Thioacetamide treatment enhanced hepatic expression of CD133 and phosphorylation signal transduction and activator of transcription 3 (STAT3), which was prevented by treatment with an antioxidant butylated hydroxyanisole. Interestingly, the risk of human HCC recurrence was positively correlated with CIRBP expression in the liver. CIRBP appears to have important oncogenic functions and its expression may be a useful biomarker for HCC risk prediction.

CIRBP and Neuroinflammation

Neuroinflammation is a critical cascade after cerebral ischemia. Excessive production of pro-inflammatory mediators in ischemia can exacerbate brain damage. It has been determined that CIRBP acts as a novel mediator of brain inflammation by stimulating the production of tumor necrosis factor-α (TNF-α) in microglia under hypoxic/ischemic stress. In CIRBP-deficient mice, the severity of brain damage and stroke inflammation is improved. Neutralizing antisera to CIRBP can attenuate TNF-α release from microglia and apoptosis of neural cell exposed to hypoxia medium. These findings provide new insights of neuroinflammation and the complex pathogenesis of ischemic stroke. Therefore, targeting CIRBP can provide new therapeutic strategies to alleviate brain inflammation and reduce neuronal damage in ischemic stroke.

CIRBP and I/R

Intestinal ischemia-reperfusion (I/R) can occur in both shock and mesenteric occlusive disease, leading to significant morbidity and mortality. In addition to localized injury, intestinal ischemia-reperfusion can cause damage to distal organs, especially the lungs. Increased levels of pro-inflammatory cytokines, myeloperoxidase, and apoptosis are hallmarks of acute respiratory distress syndrome (ARDS). Cindy Cen et al. found that during intestinal I/R intestinal cells undergo apoptosis or necrosis that release CIRBP, which is then by recognizing TLR4/MD2 complex on cell surfaces induces a sterile inflammatory response in the lungs causing ARDS (Fig. 1). That is to say, CIRBP plays a key role in local intestinal inflammation after intestinal I/R, and in enhancing the inflammation of the distal part of the lung I/R lung.

Fig. 1. Schematic model of the role of CIRP during intestinal I/R (Cen et al. Surgery, 2017)

CIRBP and Cushing’s disease

Cushing's disease is caused by a pituitary cortical malnutrition adenoma, and its pathogenesis remains unclear. Recent studies have shown that CIRBP was significantly elevated in adrenocorticotropic hormone tumors. Forced overexpression of CIRBP in the mouse AtT20 pituitary adrenocortical cell line increased corticotroph precursor hormone proopiomelanocortin (POMC) transcription, adrenocorticotropic hormone (ACTH) secretion and cell proliferation. In vivo, CIRBP overexpression promotes mouse cortical trophic tumor growth and enhances ACTH production. In mechanism, CIRBP can promote the proliferation of AtT20 cells by inducing cyclinD1 and decreasing p27 expression through the extracellular regulated protein kinases1/2 (Erk1/2) signaling pathway. Clinically, CIRBP overexpression is significantly associated with Cushing's disease recurrence. CIRBP appears to play an important role in tumorigenesis in Cushing's disease, and its expression may be a useful biomarker for tumor recurrence.

CIRBP and RA

Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovitis and other systemic involvement. The pathogenesis of RA is complex and involves a wide range of endogenous pro-inflammatory molecules, including cytokines such as TNF. Seol et al. found that the concentration of CIRBP in serum and synovial of RA patients increased compared with patients with osteoarthritis (OA). In addition, the synovial concentration of CIRBP in RA patients is well correlated with disease activity, namely DAS28-ESR / CRP. Based on these results, CIRBP mediates inflammation and is a potential marker of synovial inflammation.

In conclusion, CIRBP can promote the inflammatory response. In addition, there is growing evidence that they also play a key role in the survival and growth of cancer cells. Therefore, further research on the function of CIBRP will provide a possible direction for the understanding and future treatment of inflammatory diseases and related cancers.

References:

Wen Haoren, et al. Protein overexpression of CIRP and TLR4 in oral squamous cell carcinoma: an immunohistochemical and clinical correlation analysis. Med Oncol, 2014, 31:120
Jian Fangfang, et al. Cold inducible RNA binding protein upregulation in pituitary corticotroph adenoma induces corticotroph cell proliferation via Erk signaling pathway. Oncotarget, 2016, 7(8): 9175-9187
In Seol YOO, et al. Serum and synovial fluid concentrations of cold-inducible RNA-binding protein in patients with rheumatoid arthritis. International Journal of Rheumatic Diseases, 2018, 21:148–154
Hae Na Lee, et al. Cold-inducible RNA-binding protein, CIRP, inhibits DNA damageinduced apoptosis by regulating p53. Biochemical and Biophysical Research Communications, 2015, 464: 916e921
Liang Yu, et al. Synovial fluid concentrations of cold-inducible RNA-binding protein are associated with severity in knee osteoarthritis. Clinica Chimica Acta. 2017, 464: 44–49
Cindy Cen, et al. Deficiency in cold-inducible RNA-binding protein attenuates acute respiratory distress syndrome induced by intestinal ischemia-reperfusion. Surgery. 2017, 162(4):915-925
Toshiharu Sakurai, et al. Cold-inducible RNA-binding protein promotes the development of liver cancer. Cancer Science, 2015, 106:352–358

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