|Year : 2019 | Volume
| Issue : 3 | Page : 73-77
Multiple functions of cold-inducible RNA-binding protein in biological systems
Gang Li, Peixian Gao, Kun Luo, Hua Zhou, Yuxiang He, Hai Yuan, Xuejun Wu
Department of Vascular Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
|Date of Submission||16-Feb-2019|
|Date of Acceptance||11-Apr-2019|
|Date of Web Publication||28-Nov-2019|
Prof. Xuejun Wu
Department of Vascular Surgery, Shandong Provincial Hospital Affiliated to Shandong University, No. 324 of Jing Wu Wei Qi Road, Jinan, 250021
Source of Support: None, Conflict of Interest: None
Cold-inducible RNA-binding protein (CIRP) is an 18-kDa nuclear protein belonging to the family of cold-shock proteins. It is widely expressed in various tissues and upregulated in response to various cellular stresses. Originally, CIRP was found to stabilize specific mRNAs to facilitate their translation, which results in a survival advantage for cells under stress. Hypothermia-induced CIRP has been shown to protect the neuronal system. Recently, CIRP was found to be a multifunctional protein. In addition to acting as a damage-associated molecular pattern molecule to promote inflammation, it was also found to affect tumorigenesis. CIRP was also found to regulate telomerase activity and cardiac repolarization. Therefore, biological activities of CIRP in novel systems should receive more attention. This review will provide a brief introduction to the recent studies of CIRP with the aim of inspiring future research of novel CIRP functions.
Keywords: Cold-inducible RNA-binding protein, inflammation, stress, tumorigenesis
|How to cite this article:|
Li G, Gao P, Luo K, Zhou H, He Y, Yuan H, Wu X. Multiple functions of cold-inducible RNA-binding protein in biological systems. Vasc Invest Ther 2019;2:73-7
|How to cite this URL:|
Li G, Gao P, Luo K, Zhou H, He Y, Yuan H, Wu X. Multiple functions of cold-inducible RNA-binding protein in biological systems. Vasc Invest Ther [serial online] 2019 [cited 2020 Aug 11];2:73-7. Available from: http://www.vitonline.org/text.asp?2019/2/3/73/271903
| Introduction|| |
Cold-inducible RNA-binding protein (CIRP), also known as CIRBP and heterogeneous ribonucleoprotein (RNP) A18, is an 18-KDa nuclear protein. CIRP belongs to the family of cold-shock proteins. Both murine and human CIRPs have 172 residues with 95% similarity and contain two clearly defined domains: the N-terminal consensus sequence contains an RNA-binding domain (RBD) and the C-terminal consensus sequence contains a glycine-rich domain.,, The RBD is well conserved across many different species and binds to RNA. However, the function of the glycine-rich domain remains unknown.
CIRP was originally discovered in transcripts from mammalian cells after sustaining DNA damage (by ultraviolet [UV] irradiation or UV mimetic agents)., Subsequently, CIRP was found to be upregulated by a wide variety of cellular stressors, such as hypothermia and hypoxia.,, CIRP was also found to be widely expressed in various tissues that were not exposed to stressors, such as heart, liver, testes, and brain.,,,,,,,, CIRP is initially located in the nucleus, which migrates from the nucleus to the cytoplasm during the response to stress.,, Originally, CIRP was identified to stabilize specific mRNA to facilitate their translation, which results in a survival advantage for cell under stress.,, Xia et al. found that CIRP stabilized specific mRNAs to exhibit a protective effect against damage caused by testicular torsion/detorsion in experimental mice. Kaneko and Kibayashi  found that CIRP inhibited neurocyte apoptosis to protect stressed cells. Recently, many studies have indicated that CIRP is secreted to the extracellular environment where it acts as a damage-associated molecular pattern (DAMP) molecule that promotes inflammatory responses.,,, Moreover, anti-CIRP treatment has a protective effect in hemorrhagic shock, sepsis, liver ischemia/reperfusion injury, alcohol-induced brain injury, and cerebral ischemia. CIRP also displays an important role in tumorigenesis, such as colitis-associated cancer  and liver cancer.
Based on these studies, we think CIRP is a multifunctional protein that should receive more attention. The following section will briefly review the structure, subcellular localization, and recent studies of CIRP in different diseases, followed by the promising future gain from the intense CIRP research.
| The Structure and Subcellular Localization of Cold-Inducible RNA-Binding Protein|| |
There are two significant domains of CIRP: its N-terminal consensus sequence contains an RBD and its C-terminal consensus sequence contains a glycine-rich domain. RBD is one of the major RNA-binding motifs, also known as RNA recognition motif, RNP motif, or RNP consensus sequence.,, It includes two RNA-binding sites, an octamer designated RNP1 and a hexamer designated RNP2, which are well conserved across different species. Based on the presence of the RBD motif, CIRP also mediates RNA binding. Yang et al. found that CIRP could specifically bind to the 3'-untranslated region (UTR) of thioredoxin mRNA. CIRP also specifically binds the 3'-UTR of replication protein A and Ataxia telangiectasia-mutated and Rad3-related mRNA.,
The RNA-binding proteins play a very important role in regulating gene expression. In this process, the RNA-binding proteins are involved in various posttranscriptional aspects, such as nuclear/cytoplasmic transport, RNA localization, RNA stability, and translation. The mRNA translation is the key control point for cells under stress. Translation initiation can be regulated at both the 5' and the 3' end of an mRNA transcript. The RNA-binding proteins can also affect the stability of a transcript when binding to the 3'-UTR. Regulation of protein translation is recognized as the key point of the cellular response following stress. Moreover, modification of the protein synthesis patterns was recognized as an early change following stress. Downregulation of protein synthesis is an adaptive cellular response to stress, which conserves necessary resources for survival. CIRP binds the 5'-UTR or 3'-UTR of specific mRNAs and alters initiation of translation and/or the stability of the transcripts to facilitate their translation, which results in a survival advantage for cells under stress.,,,
The subcellular localization of CIRP is dependent on stress conditions., CIRP is primarily found in the nucleus of unstressed cells., Originally, CIRP was thought to remain in the nucleus of mammalian cells exposed to hypothermic shock. In contrast, De Leeuw et al. found that CIRP migrates from the nucleus to the cytoplasm under oxidative stress by a methylation-dependent mechanism. Yang and Carrier  also found that UV radiation triggered CIRP migration from the nucleus to the cytoplasm. Recently, Qiang et al. found that CIRP was secreted to extracellular in the hemorrhagic and septic shock. Now, increasing studies have found that CIRP is secreted to extracellular in response to different stresses.,
| The Multifunction of Cold-Inducible RNA-Binding Protein|| |
Originally, CIRP was found to be upregulated in response to UV irradiation or UV mimetic agents. Subsequently, Nishiyama et al. found that hypothermia could also facilitate the expression of CIRP in mammalian cells., Wellmann et al. found that CIRP was upregulated in response to the hypoxia by an hypoxia-inducible factor-1-independent mechanism. The increasing number of studies indicate that CIRP is upregulating in response to various cellular stressors and CIRP is a general stress-responsive protein.,,,
However, CIRP acts differently in various biological systems. Originally, CIRP was proposed to inhibit mammalian cell proliferation. Nishiyama et al. found that downregulation of CIRP using antisense oligodeoxynucleotides restored growth that was reduced by hypothermia, while overexpression of CIRP decreased the growth rate of mouse fibroblasts at 37°C through prolonging the G1 phase of the cell cycle. This research indicated that CIRP suppressed the growth of mouse fibroblasts. In contrast, Hong et al. found that downregulation of CIRP did not improve hypothermic growth of Chinese hamster ovary cells. Subsequently, Artero-Castro et al. found that CIRP stimulated proliferation of primary cells by upregulating extracellular signal-regulated kinases 1 and 2 (ERK1/2) phosphorylation. Accordingly, downregulation of CIRP impaired cell proliferation and decreased ERK1/2 phosphorylation. Masuda et al. reported that CIRP promoted proliferation of immature male germ cells in mice. They also found that CIRP promoted cell cycle progression from G0–G1 to G–S phase in mouse embryonic fibroblasts. From these studies, CIRP seems to promote cell proliferation and might be involved with the cell cycle.
Recently, some studies indicated that CIRP played an important role in protecting cells against apoptosis.,, Sakurai et al. found that CIRP protected against tumor necrosis factor (TNF)-α-induced apoptosis of mouse fibroblasts both at 37°C and 32°C through activation of the ERK pathway. Li et al. also found that hypothermia-induced CIRP inhibited H2O2-induced apoptosis of rat cortical neurons and thereby exerted a neuroprotective effect. Their study examined one of the cerebral protective pathways under hypothermia. Other researchers also found that hypothermia-induced CIRP has a neuroprotective effect by suppressing the mitochondrial apoptosis pathway., This may be the molecular mechanism of hypothermia-induced neuroprotection. Recently, Liu et al. found that recombinant CIRP (rCIRP) significantly improved viability of nero2a cells following H2O2 stimulation. Hence, CIRP was identified as a neuroprotective cytokine. In addition to being a novel neuroprotective agent, CIRP also exhibited a testicular cell protective effect in testicular torsion/detorsion injury  and cryptorchidism-induced testicular damage. CIRP protects testes by regulating the stabilization of specific mRNAs in the testes of the experimental mice.
In contrast, recent studies have found that CIRP acts as a DAMP molecule with pro-inflammatory cytokine-like properties. Brochu et al. found that CIRP upregulated interleukin-1β expression in a variety of cell types under stress. Subsequently, Qiang et al. found that CIRP was secreted to the extracellular space and bound to the cell surface receptor TLR4 to trigger inflammatory responses in hemorrhagic shock and sepsis. They also found that the rCIRP stimulated TNF-α production in RAW 264.7 cells. Rajayer et al. demonstrated that alcohol could stimulate BV2 cells (mouse microglia) to secrete CIRP into the medium, and CIRP -/- mice had an attenuated inflammatory response following alcohol exposure. Zhou et al. showed that rCIRP directly stimulated TNF-α production in BV2 cells. In their study, the CIRP -/- mice showed attenuated inflammation and neuron injury in cerebral ischemia. Then, CIRP was also found to mediate inflammation in liver ischemia/reperfusion injury, colitis, and wound healing progression. Moreover, clinical studies have found that increased CIRP levels in peripheral blood is a potential predictor of poor prognosis during sepsis. Based on all these studies, CIRP was identified as a new pro-inflammatory cytokine.
| The Role of Cold-Inducible RNA-Binding Protein in Tumorigenesis|| |
Apoptosis is a crucial form of programmed cell death during development and homeostasis in both vertebrates and invertebrates. Apoptosis is also considered the major method of eradicating tumors. CIRP inhibits apoptosis by regulating p53 or suppressing mitochondrial apoptosis., In light of these observations, CIRP may be involved in tumorigenesis.
In a previous study, Artero-Castro et al. found that CIRP was upregulated in many tumors, such as liver-pancreas, gastric, nervous system, lung, kidney, ovarian, breast, colon, and prostate tumors. In their study, they also showed that central nervous system-related tumors have a significant correlation between P-ERK1/2 and CIRP (P = 0.05), and the association with liver-pancreas carcinomas approached significant levels (P = 0.08). Lleonart has recognized CIRP as a new proto-oncogene. Recently, Sakurai et al. found that CIRP mediated the tumorigenesis of colitis-associated cancer. In their research, CIRP -/- mice showed a significant decrease in the number and maximum size of tumors compared with wild-type (WT) mice in a colitis-associated cancer model. They also found that transplantation of CIRP -/- bone marrow into WT mice reduced tumorigenesis, indicating that CIRP promoted tumorigenesis through hematopoietic cells. Sakurai et al. also found that CIRP -/- mice had fewer and smaller tumors compared with WT mice in diethylnitrosamine-induced hepatocarcinogenesis. Their clinical study found that the risk of human hepatocellular carcinoma recurrence was positively correlated with CIRP expression in the liver. Wang et al. also found that the proliferation, invasion, and recurrence of pituitary adenomas were closely related to the high expression of CIRP. Subsequently, high expression of CIRP was found in oral squamous cell carcinoma and pituitary corticotroph adenoma and also closely correlates with the recurrence of these diseases., Without a doubt, CIRP affects tumorigenesis and should be further investigated in other tumors.
| Conclusion and Future Directions|| |
Here, we reviewed recent studies of CIRP. It is now widely accepted that CIRP is a multifunctional protein with many biological activities. However, the various biological activities of CIRP are not consistent. In most neuronal studies, hypothermia-induced CIRP showed a protective effect on the neuronal system. In contrast, Zhou et al. found that CIRP displayed pro-inflammatory cytokine-like properties in the cerebral ischemia. The role of CIRP in neuronal systems needs further research. Other studies highlight that CIRP acts as a pro-inflammatory cytokine and induces organ injury in many inflammation-associated diseases. In addition, CIRP partially affects tumorigenesis and was identified as a new oncogene. CIRP was found to regulate telomerase activity in a temperature-dependent manner  as well as regulating cardiac repolarization by targeting transient outward potassium channels. By now, it is evident that the role of CIRP in other biological activities should receive more attention.
Recently, Ren et al. found that TLR4 was coexpressed with CIRP in the oral squamous cell carcinoma. TLR4 is a cellular surface pattern-recognition receptor that mediates the innate immune response. It can recognize several endogenous molecules, such as HMGB1 and heat shock protein 70.,, Qiang et al. also found that CIRP interacts with TLR4 to induce inflammation in hemorrhagic shock and sepsis. In their study, TLR4-/- mice showed a significant attenuated organ injury following rCIRP infusion compared with the WT mice. These results suggest that TLR4 is the major receptor of CIRP. When TLR4 is activated, it activates intracellular signaling molecules through the MyD88-dependent or TRIF-dependent pathways that ultimately activate nuclear factor (NF)-κB to induce downstream cytokine expression. Zhou et al. found that rCIRP activates NF-κB and induces expression of its downstream cytokine (TNF-α). Brochu et al. found that CIRP upregulated interleukin-1β expression in an NF-κB-dependent manner. Furthermore, the TLR4/NF-κB-signaling pathway may mediate CIRP-associated biological activities and needs more attention in future studies.
This work was supported by grant from the National Natural Science Foundation of China (No. 8157020626; No. 81670435; No. 81800409), the Medicine and Health Science Technology Development Plan of Shandong (No. 2016WS0429), and the Major Research and Development Program of Shandong (No. 2017GSF218074).
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Nishiyama H, Itoh K, Kaneko Y, Kishishita M, Yoshida O, Fujita J, et al.
A glycine-rich RNA-binding protein mediating cold-inducible suppression of mammalian cell growth. J Cell Biol 1997;137:899-908.
Qiang X, Yang WL, Wu R, Zhou M, Jacob A, Dong W, et al.
Cold-inducible RNA-binding protein (CIRP) triggers inflammatory responses in hemorrhagic shock and sepsis. Nat Med 2013;19:1489-95.
Nishiyama H, Higashitsuji H, Yokoi H, Itoh K, Danno S, Matsuda T, et al.
Cloning and characterization of human CIRP (cold-inducible RNA-binding protein) cDNA and chromosomal assignment of the gene. Gene 1997;204:115-20.
Lleonart ME. A new generation of proto-oncogenes: Cold-inducible RNA binding proteins. Biochim Biophys Acta 2010;1805:43-52.
Brochu C, Cabrita MA, Melanson BD, Hamill JD, Lau R, Pratt MA, et al.
NF-κB-dependent role for cold-inducible RNA binding protein in regulating interleukin 1β. PLoS One 2013;8:e57426.
Fornace AJ Jr. Alamo I Jr. Hollander MC. DNA damage-inducible transcripts in mammalian cells. Proc Natl Acad Sci U S A 1988;85:8800-4.
Sheikh MS, Carrier F, Papathanasiou MA, Hollander MC, Zhan Q, Yu K, et al.
Identification of several human homologs of hamster DNA damage-inducible transcripts. Cloning and characterization of a novel UV-inducible cDNA that codes for a putative RNA-binding protein. J Biol Chem 1997;272:26720-6.
Wellmann S, Bührer C, Moderegger E, Zelmer A, Kirschner R, Koehne P, et al.
Oxygen-regulated expression of the RNA-binding proteins RBM3 and CIRP by a HIF-1-independent mechanism. J Cell Sci 2004;117:1785-94.
Nishiyama H, Danno S, Kaneko Y, Itoh K, Yokoi H, Fukumoto M, et al.
Decreased expression of cold-inducible RNA-binding protein (CIRP) in male germ cells at elevated temperature. Am J Pathol 1998;152:289-96.
Nishiyama H, Xue JH, Sato T, Fukuyama H, Mizuno N, Houtani T, et al.
Diurnal change of the cold-inducible RNA-binding protein (Cirp) expression in mouse brain. Biochem Biophys Res Commun 1998;245:534-8.
Xia ZP, Zheng XM, Zheng H, Liu XJ, Liu GY, Wang XH, et al.
Downregulation of cold-inducible RNA-binding protein activates mitogen-activated protein kinases and impairs spermatogenic function in mouse testes. Asian J Androl 2012;14:884-9.
Chen L, Tian Q, Wang W. Association between CIRP expression and hypoxic-ischemic brain injury in neonatal rats. Exp Ther Med 2019;18:1515-20.
Chen M, Fu H, Zhang J, Huang H, Zhong P. CIRP downregulation renders cardiac cells prone to apoptosis in heart failure. Biochem Biophys Res Commun 2019;517:545-50.
Liu P, Yao R, Shi H, Liu Y, Lian S, Yang Y, et al.
Effects of cold-inducible RNA-binding protein (CIRP) on liver glycolysis during acute cold exposure in C57BL/6 mice. Int J Mol Sci 2019;20:E1470.
De Leeuw F, Zhang T, Wauquier C, Huez G, Kruys V, Gueydan C, et al.
The cold-inducible RNA-binding protein migrates from the nucleus to cytoplasmic stress granules by a methylation-dependent mechanism and acts as a translational repressor. Exp Cell Res 2007;313:4130-44.
Yang R, Weber DJ, Carrier F. Post-transcriptional regulation of thioredoxin by the stress inducible heterogenous ribonucleoprotein A18. Nucleic Acids Res 2006;34:1224-36.
Morf J, Rey G, Schneider K, Stratmann M, Fujita J, Naef F, et al.
Cold-inducible RNA-binding protein modulates circadian gene expression posttranscriptionally. Science 2012;338:379-83.
Yang C, Carrier F. The UV-inducible RNA-binding protein A18 (A18 hnRNP) plays a protective role in the genotoxic stress response. J Biol Chem 2001;276:47277-84.
Yang R, Zhan M, Nalabothula NR, Yang Q, Indig FE, Carrier F, et al.
Functional significance for a heterogenous ribonucleoprotein A18 signature RNA motif in the 3'-untranslated region of ataxia telangiectasia mutated and rad3-related (ATR) transcript. J Biol Chem 2010;285:8887-93.
Xia Z, Zheng X, Zheng H, Liu X, Yang Z, Wang X, et al.
Cold-inducible RNA-binding protein (CIRP) regulates target mRNA stabilization in the mouse testis. FEBS Lett 2012;586:3299-308.
Kaneko T, Kibayashi K. Mild hypothermia facilitates the expression of cold-inducible RNA-binding protein and heat shock protein 70.1 in mouse brain. Brain Res 2012;1466:128-36.
Godwin A, Yang WL, Sharma A, Khader A, Wang Z, Zhang F, et al.
Blocking cold-inducible RNA-binding protein protects liver from ischemia-reperfusion injury. Shock 2015;43:24-30.
Rajayer SR, Jacob A, Yang WL, Zhou M, Chaung W, Wang P, et al.
Cold-inducible RNA-binding protein is an important mediator of alcohol-induced brain inflammation. PLoS One 2013;8:e79430.
Zhou M, Yang WL, Ji Y, Qiang X, Wang P. Cold-inducible RNA-binding protein mediates neuroinflammation in cerebral ischemia. Biochim Biophys Acta 2014;1840:2253-61.
Sakurai T, Kashida H, Watanabe T, Hagiwara S, Mizushima T, Iijima H, et al.
Stress response protein cirp links inflammation and tumorigenesis in colitis-associated cancer. Cancer Res 2014;74:6119-28.
Sakurai T, Yada N, Watanabe T, Arizumi T, Hagiwara S, Ueshima K, et al.
Cold-inducible RNA-binding protein promotes the development of liver cancer. Cancer Sci 2015;106:352-8.
Kenan DJ, Query CC, Keene JD. RNA recognition: Towards identifying determinants of specificity. Trends Biochem Sci 1991;16:214-20.
Burd CG, Dreyfuss G. Conserved structures and diversity of functions of RNA-binding proteins. Science 1994;265:615-21.
Sheikh MS, Fornace AJ Jr. Regulation of translation initiation following stress. Oncogene 1999;18:6121-8.
Hinnebusch AG. The eIF-2 alpha kinases: Regulators of protein synthesis in starvation and stress. Semin Cell Biol 1994;5:417-26.
Hong JK, Kim YG, Yoon SK, Lee GM. Down-regulation of cold-inducible RNA-binding protein does not improve hypothermic growth of chinese hamster ovary cells producing erythropoietin. Metab Eng 2007;9:208-16.
Artero-Castro A, Callejas FB, Castellvi J, Kondoh H, Carnero A, Fernández-Marcos PJ, et al.
Cold-inducible RNA-binding protein bypasses replicative senescence in primary cells through extracellular signal-regulated kinase 1 and 2 activation. Mol Cell Biol 2009;29:1855-68.
Masuda T, Itoh K, Higashitsuji H, Higashitsuji H, Nakazawa N, Sakurai T, et al.
Cold-inducible RNA-binding protein (Cirp) interacts with dyrk1b/Mirk and promotes proliferation of immature male germ cells in mice. Proc Natl Acad Sci U S A 2012;109:10885-90.
Sakurai T, Itoh K, Higashitsuji H, Nonoguchi K, Liu Y, Watanabe H, et al.
Cirp protects against tumor necrosis factor-alpha-induced apoptosis via activation of extracellular signal-regulated kinase. Biochim Biophys Acta 2006;1763:290-5.
Li S, Zhang Z, Xue J, Liu A, Zhang H. Cold-inducible RNA binding protein inhibits H2
-induced apoptosis in rat cortical neurons. Brain Res 2012;1441:47-52.
Zhang HT, Xue JH, Zhang ZW, Kong HB, Liu AJ, Li SC, et al.
Cold-inducible RNA-binding protein inhibits neuron apoptosis through the suppression of mitochondrial apoptosis. Brain Res 2015;1622:474-83.
Wu L, Sun HL, Gao Y, Hui KL, Xu MM, Zhong H, et al.
Therapeutic hypothermia enhances cold-inducible RNA-binding protein expression and inhibits mitochondrial apoptosis in a rat model of cardiac arrest. Mol Neurobiol 2017;54:2697-705.
Liu J, Xue J, Zhang H, Li S, Liu Y, Xu D, et al.
Cloning, expression, and purification of cold inducible RNA-binding protein and its neuroprotective mechanism of action. Brain Res 2015;1597:189-95.
Zhou KW, Zheng XM, Yang ZW, Zhang L, Chen HD. Overexpression of CIRP may reduce testicular damage induced by cryptorchidism. Clin Invest Med 2009;32:E103-11.
Idrovo JP, Jacob A, Yang WL, Wang Z, Yen HT, Nicastro J, et al.
A deficiency in cold-inducible RNA-binding protein accelerates the inflammation phase and improves wound healing. Int J Mol Med 2016;37:423-8.
Zhou Y, Dong H, Zhong Y, Huang J, Lv J, Li J, et al.
The cold-inducible RNA-binding protein (CIRP) level in peripheral blood predicts sepsis outcome. PLoS One 2015;10:e0137721.
Li G, Chang H, Zhai YP, Xu W. Targeted silencing of inhibitors of apoptosis proteins with siRNAs: A potential anti-cancer strategy for hepatocellular carcinoma. Asian Pac J Cancer Prev 2013;14:4943-52.
Lee HN, Ahn SM, Jang HH. Cold-inducible RNA-binding protein, CIRP, inhibits DNA damage-induced apoptosis by regulating p53. Biochem Biophys Res Commun 2015;464:916-21.
Wang M, Zhang H, Heng X, Pang Q, Sun A. Expression of cold-inducible RNA-binding protein (CIRP) in pituitary adenoma and its relationships with tumor recurrence. Med Sci Monit 2015;21:1256-60.
Ren WH, Zhang LM, Liu HQ, Gao L, Chen C, Qiang C, 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 F, Chen Y, Ning G, Fu W, Tang H, Chen X, et al.
Cold inducible RNA binding protein upregulation in pituitary corticotroph adenoma induces corticotroph cell proliferation via erk signaling pathway. Oncotarget 2016;7:9175-87.
Zhang Y, Wu Y, Mao P, Li F, Han X, Zhang Y, et al.
Cold-inducible RNA-binding protein CIRP/hnRNP A18 regulates telomerase activity in a temperature-dependent manner. Nucleic Acids Res 2016;44:761-75.
Li J, Xie D, Huang J, Lv F, Shi D, Liu Y, et al.
Cold-inducible RNA-binding protein regulates cardiac repolarization by targeting transient outward potassium channels. Circ Res 2015;116:1655-9.
Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: Update on toll-like receptors. Nat Immunol 2010;11:373-84.
Bianchi ME. DAMPs, PAMPs and alarmins: All we need to know about danger. J Leukoc Biol 2007;81:1-5.
Park JS, Svetkauskaite D, He Q, Kim JY, Strassheim D, Ishizaka A, et al.
Involvement of toll-like receptors 2 and 4 in cellular activation by high mobility group box1 protein. J Biol Chem 2004;279:7370-7.