Heterogeneous nuclear ribonucleoprotein A18 (hnRNP A18) (hnRNP A18)

Heterogeneous nuclear ribonucleoprotein A18 (hnRNP A18), also known as Cold-inducible RNA-binding protein (CIRBP), is a multifunctional RNA-binding protein (RBP) that plays a critical role in post-transcriptional gene regulation and the cellular stress response (Nishiyama et al., 1997; Sheikh et al., 1997). Under normal physiological conditions, it is primarily localized in the nucleus, but it translocates to the cytoplasm in response to stressors such as hypoxia, UV radiation, and cold shock (Chang et al., 2016; Solano-Gonzalez et al., 2021). In the cytoplasm, hnRNP A18 binds to specific signature motifs in the 3' untranslated regions (UTRs) of target mRNAs, including those encoding pro-survival factors like Thioredoxin (Trx), VEGF, and RPA, thereby enhancing their stability and translation (Solano-Gonzalez et al., 2021; Nucleic Acids Res). hnRNP A18 is frequently overexpressed in various solid tumors, such as melanoma, breast, and colon cancer, where it promotes tumor progression and immune evasion by upregulating the immune checkpoint protein CTLA-4 (Solano-Gonzalez et al., 2021). Due to its role in coordinating pro-survival gene expression, hnRNP A18 has emerged as a promising therapeutic target in oncology (Chang et al., 2016; Oncotarget). Recent drug discovery efforts have identified small molecule inhibitors, such as SF-8-155 and Anticancer agent 312, which disrupt the interaction between hnRNP A18 and its target transcripts to suppress tumor growth and enhance immune recognition in preclinical models (Solano-Gonzalez et al., 2021; MedChemExpress).

Other names

Cold-inducible RNA-binding proteinCIRBPCIRPA18 hnRNP

Small molecule inhibition of the RNA recognition motif (RRM) to block binding to target mRNAs, thereby inhibiting protein translation of pro-survival and immune checkpoint genes.