Lrrc58-flox Mouse

Lrrc58, also known as lrr-2 in Caenorhabditis elegans, is involved in sulfur metabolism. It post-translationally regulates the levels of cysteine dioxygenase (cdo-1/CDO1), thus playing a role in cysteine and hydrogen sulfide (H2S) production [2]. In C. elegans, it impacts the interaction with Actinobacteria from its natural microbial environment, as mutations in lrr-2/LRRC58 can affect the growth rate of the nematode on Actinobacteria [2].

In human studies, LRRC58 has been associated with several cancers. In colorectal cancer, it was identified as one of the N6-methyladenosine (m6A)-modified genes related to recurrence, potentially serving as a predictive biomarker or therapeutic target [1]. In prostate cancer, it was part of a set of potential biomarkers proposed for the detection of the disease and discrimination between tumors with different malignancy and aggressiveness, with its methylation being detected in a significant number of prostate tumors [3,4].

In addition to its role in cancer, LRRC58 also plays an important function in metabolic processes. It acts as a substrate adaptor for an E3 ubiquitin ligase, mediating the proteasomal degradation of cysteine dioxygenase 1 (CDO1). CDO1 is the rate-limiting enzyme in the process of cysteine catabolism to taurine. The intracellular level of cysteine regulates LRRC58-mediated CDO1 degradation. When LRRC58 function is deficient, CDO1 becomes stabilized, thereby promoting the conversion of cysteine to taurine, which in turn affects cholesterol metabolism and leads to a decrease in liver cholesterol levels[5].

In conclusion, LRRC58 plays important roles in biological processes related to sulfur metabolism in C. elegans and is associated with cancer-related processes in humans, especially colorectal and prostate cancers. The identification of its role in these disease-related contexts through various research models provides potential directions for future diagnostic and therapeutic development.

References:

1.Zhu, Qianru, Huang, Xingxing, Yu, Shuxian, Yu, Lili, Wu, Qibiao. 2022. Identification of genes modified by N6-methyladenosine in patients with colorectal cancer recurrence. In Frontiers in genetics, 13, 1043297. doi:10.3389/fgene.2022.1043297. https://pubmed.ncbi.nlm.nih.gov/36324506/

2.Patange, Om, Breen, Peter, Arsuffi, Giulia, Ruvkun, Gary. 2025. Hydrogen sulfide mediates the interaction between C. elegans and Actinobacteria from its natural microbial environment. In Cell reports, 44, 115170. doi:10.1016/j.celrep.2024.115170. https://pubmed.ncbi.nlm.nih.gov/39786993/

3.Dmitriev, Alexey A, Rosenberg, Eugenia E, Krasnov, George S, Senchenko, Vera N, Kashuba, Vladimir I. 2015. Identification of Novel Epigenetic Markers of Prostate Cancer by NotI-Microarray Analysis. In Disease markers, 2015, 241301. doi:10.1155/2015/241301. https://pubmed.ncbi.nlm.nih.gov/26491211/

4.Vozianov, S O, Kashuba, V I, Grygorenko, V M, Bondarenko, Yu M, Vikarchuk, M V. . [IDENTIFICATION OF A NEW DIAGNOSTIC MARKERS OF PROSTATIC CANCER, USING NOTI-MICROCHIPS]. In Klinichna khirurhiia, , 54-7. doi:. https://pubmed.ncbi.nlm.nih.gov/27434957/

5.Xiao, H., et al. (2025). Covariation MS uncovers a protein that controls cysteine catabolism. Nature. https://doi.org/10.1038/s41586-025-09535-5.