Rbks-KO Mouse

Rbks, which encodes ribokinase, is the first enzyme for ribose metabolism in vivo [4]. Ribokinase is involved in the pentose phosphate pathway, which is crucial for generating energy and precursors for nucleotides and amino acids, thus supporting cell growth [6,7]. The gene is important in various biological processes, potentially influencing metabolism, cell cycle regulation, and more, with its study in genetic models offering insights into its functions.

In pancreatic ductal adenocarcinoma cells (Panc-1), silencing of Rbks did not have an anti-proliferative effect, but it did sensitize the cells to Doxorubicin and Gemcitabine, suggesting a chemo-resistant role [2]. In human fibroblasts, silencing Rbks led to an increased fraction of cells entering the S phase, indicating its role in DNA replication control [6]. In a study on metabolic dysfunction-associated steatotic liver disease (MASLD), Rbks was identified as a candidate protein target, and it mediated the association of obesity and MASLD, and also had an effect on MASLD independent of obesity [1]. In whole-exome rare-variant analysis, rare coding variation in Rbks was associated with cognitive performance in relation to Alzheimer's disease [3]. In recurrent implantation failure, Rbks was identified as one of the characteristic genes, suggesting its involvement in endometrial metabolic characteristics related to this condition [5].

In conclusion, Rbks plays diverse roles in multiple biological processes and disease conditions. Studies using gene-silencing or other loss-of-function approaches, similar to what could be achieved in gene knockout models, have revealed its functions in cancer cell drug resistance, DNA replication, metabolic diseases, neurodegenerative disease-related cognitive performance, and reproductive-related endometrial metabolism. Understanding Rbks can potentially offer new therapeutic strategies for these associated diseases.

References:

1. Liu, Jun, Hu, Sile, Chen, Lingyan, van Duijn, Cornelia M, Howson, Joanna M M. 2023. Profiling the genome and proteome of metabolic dysfunction-associated steatotic liver disease identifies potential therapeutic targets. In medRxiv : the preprint server for health sciences, , . doi:10.1101/2023.11.30.23299247. https://pubmed.ncbi.nlm.nih.gov/38076879/

2. Al Hanjori, Ahmad S, Alshaer, Walhan, Al-Anati, Bayan, Wehaibi, Suha, Zihlif, Malek. . Studying the Anti-Tumor Effects of siRNA Gene Silencing of Some Metabolic Genes in Pancreatic Ductal Adenocarcinoma. In Current molecular pharmacology, 14, 604-619. doi:10.2174/1874467213666201012162250. https://pubmed.ncbi.nlm.nih.gov/33045974/

3. Küçükali, Fahri, Neumann, Alexander, Van Dongen, Jasper, Van Broeckhoven, Christine, Sleegers, Kristel. 2022. Whole-exome rare-variant analysis of Alzheimer's disease and related biomarker traits. In Alzheimer's & dementia : the journal of the Alzheimer's Association, 19, 2317-2331. doi:10.1002/alz.12842. https://pubmed.ncbi.nlm.nih.gov/36464806/

4. Liu, Yan, Li, Tong-Ruei R, Xu, Cong, Xu, Tian. 2016. Ribose Accelerates Gut Motility and Suppresses Mouse Body Weight Gaining. In International journal of biological sciences, 12, 701-9. doi:10.7150/ijbs.13635. https://pubmed.ncbi.nlm.nih.gov/27194947/

5. Fan, Yuan, Shi, Cheng, Huang, Nannan, Tian, Li, Wang, Jianliu. 2023. Recurrent Implantation Failure: Bioinformatic Discovery of Biomarkers and Identification of Metabolic Subtypes. In International journal of molecular sciences, 24, . doi:10.3390/ijms241713488. https://pubmed.ncbi.nlm.nih.gov/37686293/

6. Fornalewicz, Karolina, Wieczorek, Aneta, Węgrzyn, Grzegorz, Łyżeń, Robert. 2017. Silencing of the pentose phosphate pathway genes influences DNA replication in human fibroblasts. In Gene, 635, 33-38. doi:10.1016/j.gene.2017.09.005. https://pubmed.ncbi.nlm.nih.gov/28887160/

7. Kim, Yunna, Kim, Eun-Young, Seo, You-Mi, Lee, Woo-Sik, Lee, Kyung-Ah. 2012. Function of the pentose phosphate pathway and its key enzyme, transketolase, in the regulation of the meiotic cell cycle in oocytes. In Clinical and experimental reproductive medicine, 39, 58-67. doi:10.5653/cerm.2012.39.2.58. https://pubmed.ncbi.nlm.nih.gov/22816071/