Rnasel-KO Mouse

RNASEL, encoding ribonuclease L, is a terminal component of antiviral and Interferon (IFN) pathways in mammalian cells [4]. It functions in RNA turnover and is part of the 2',5'-oligoadenylate-synthetase-directed ribonuclease L pathway, which blocks viral transcription and degrades viral RNA to control viral replication [8]. Genetic studies, including those on its polymorphisms, are valuable in understanding its role in disease.

Regarding its association with diseases, numerous studies have explored the relationship between RNASEL gene polymorphisms and cancer risk. A meta-analysis of 40 studies found that rs627928 polymorphism may promote prostate cancer development in overall and white populations, while rs486907 was not associated with prostate cancer risk [1]. In Afro-Caribbeans, common variation in RNASEL or its inhibitor ABCE1 did not significantly contribute to prostate cancer risk [3]. A meta-analysis of 21 case-control studies suggested that the RNASEL-1385G/A (rs486907) polymorphism is associated with increased cancer risk in African descendants [6]. Another meta-analysis of 19 case-control studies showed that RNASEL Asp541Glu and Arg462Gln polymorphisms were not related to overall prostate cancer risk, especially in Caucasians, but the Asp541Glu polymorphism might be a risk factor for sporadic prostate cancer [7]. RNASEL:p.Glu265* may be a genetic modifier of risk for early-onset breast cancer in carriers of high-risk mutations [2]. Also, RNASEL and MIR146A SNP-SNP interaction may influence susceptibility to non-melanoma skin cancer, suggesting that RNASEL is controlled by miR-146a [5]. RNASEL germline variants Glu265X and Arg462Gln may contribute to the tumorigenesis of sporadic and familial pancreatic cancer [9].

In conclusion, RNASEL is crucial in antiviral and IFN pathways, playing a role in RNA turnover. Research on its polymorphisms through genetic models has revealed associations with various cancers, including prostate, breast, non-melanoma skin, and pancreatic cancer. These findings contribute to understanding the genetic basis of cancer susceptibility and potentially developing targeted prevention and treatment strategies.

References:

1. Xia, Jun, Sun, Rulin. 2019. Evidence from 40 Studies that 2 Common Single-Nucleotide Polymorphisms (SNPs) of RNASEL Gene Affect Prostate Cancer Susceptibility: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-Compliant Meta-Analysis. In Medical science monitor : international medical journal of experimental and clinical research, 25, 8315-8325. doi:10.12659/MSM.917715. https://pubmed.ncbi.nlm.nih.gov/31686670/

2. Nguyen-Dumont, Tú, Teo, Zhi L, Hammet, Fleur, Hopper, John L, Southey, Melissa C. 2018. Is RNASEL:p.Glu265* a modifier of early-onset breast cancer risk for carriers of high-risk mutations? In BMC cancer, 18, 165. doi:10.1186/s12885-018-4028-z. https://pubmed.ncbi.nlm.nih.gov/29422015/

3. Shea, Patrick R, Ishwad, Chandramohan S, Bunker, Clareann H, Kuller, Lewis H, Ferrell, Robert E. . RNASEL and RNASEL-inhibitor variation and prostate cancer risk in Afro-Caribbeans. In The Prostate, 68, 354-9. doi:10.1002/pros.20687. https://pubmed.ncbi.nlm.nih.gov/18189233/

4. Maleki, A, Ravanshad, M, Kouhkan, F. . Increase in RNASEL gene expression by miR-29-3p inhibitors in HEK293T cells. In Epidemiologie, mikrobiologie, imunologie : casopis Spolecnosti pro epidemiologii a mikrobiologii Ceske lekarske spolecnosti J.E. Purkyne, 69, 116-120. doi:. https://pubmed.ncbi.nlm.nih.gov/33086852/

5. Farzan, Shohreh F, Karagas, Margaret R, Christensen, Brock C, Kuriger, Jacquelyn K, Nelson, Heather H. 2014. RNASEL and MIR146A SNP-SNP interaction as a susceptibility factor for non-melanoma skin cancer. In PloS one, 9, e93602. doi:10.1371/journal.pone.0093602. https://pubmed.ncbi.nlm.nih.gov/24699816/

6. Zhang, Li-Feng, Mi, Yuan-Yuan, Qin, Chao, Feng, Ning-Han, Zhang, Wei. 2011. RNASEL -1385G/A polymorphism and cancer risk: a meta-analysis based on 21 case-control studies. In Molecular biology reports, 38, 5099-105. doi:10.1007/s11033-010-0657-2. https://pubmed.ncbi.nlm.nih.gov/21221811/

7. Wei, Bingbing, Xu, Zhuoqun, Ruan, Jun, Lu, Peng, Shao, Jianfeng. 2011. RNASEL Asp541Glu and Arg462Gln polymorphisms in prostate cancer risk: evidences from a meta-analysis. In Molecular biology reports, 39, 2347-53. doi:10.1007/s11033-011-0985-x. https://pubmed.ncbi.nlm.nih.gov/21656378/

8. Sadler, Anthony J, Williams, Bryan R G. . Interferon-inducible antiviral effectors. In Nature reviews. Immunology, 8, 559-68. doi:10.1038/nri2314. https://pubmed.ncbi.nlm.nih.gov/18575461/

9. Bartsch, Detlef K, Fendrich, Volker, Slater, Emily P, Neoptolemos, John P, Kress, Ralf. . RNASEL germline variants are associated with pancreatic cancer. In International journal of cancer, 117, 718-22. doi:. https://pubmed.ncbi.nlm.nih.gov/15981205/