Rps6kb2-KO Mouse

Rps6kb2, also known as ribosomal protein S6 kinase B2, is a downstream effector of mTOR. It is involved in pathways such as regulation of cell growth, insulin, and inflammation, and is important for processes like cell cycle regulation [3,4,6]. It has been associated with various biological processes and diseases, highlighting its overall biological importance. Genetic models can be valuable for studying its functions.

Integrated transcriptome analysis indicates that Rps6kb2 may serve as a potential biomarker for predicting breast cancer metastasis [1]. In colorectal cancer, ALYREF recruits ELAVL1 to promote the m5C recognition and nuclear export of Rps6kb2 transcripts, facilitating colorectal tumorigenesis [2]. It is overexpressed in head and neck cancer, breast cancer, and prostate cancer, making it a potential target for cancer therapeutics [3]. Analyses also suggest that Rps6kb2 is aberrantly expressed in most cancers, associated with poor prognosis, and involved in cancer cell apoptosis, migration, and immune processes, with validation in hepatocellular carcinoma where it can upregulate proinflammatory cytokines [4]. NSUN6, an RNA methyltransferase, controls glioblastoma response to temozolomide via 5mC-mediated regulation of Rps6KB2 [5]. Genetic variation in Rps6KB2 is associated with the risk of developing colon cancer [6]. In breast cancer, differential expression of Rps6KB2 by race may play a role in racial disparities of treatment resistance and outcomes [7]. In Chinese tongue sole, rps6kb2 is related to flatfish metamorphosis, being significantly expressed during the metamorphic climax stage [8]. The adjacent lncRNA AP003419.16 and Rps6KB2 are both increased in patients with idiopathic pulmonary fibrosis, suggesting a potential molecular hypothesis for IPF occurrence during aging [9].

In conclusion, Rps6kb2 is involved in multiple biological processes and diseases, including cancer and fibrosis. Its role in cell cycle regulation, cancer cell behavior, and immune processes has been revealed through various studies. The use of genetic models could further enhance our understanding of Rps6kb2's functions in these disease areas, potentially providing new targets for treatment.

References:

1. Chen, Gang, Zhang, Kun, Liang, Zhi, Cong, Yizi, Qiao, Guangdong. 2023. Integrated transcriptome analysis identifies APPL1/RPS6KB2/GALK1 as immune-related metastasis factors in breast cancer. In Open medicine (Warsaw, Poland), 18, 20230732. doi:10.1515/med-2023-0732. https://pubmed.ncbi.nlm.nih.gov/37273920/

2. Zhong, Longhua, Wu, Jingxun, Zhou, Bingqian, Ye, Feng, Lin, Xiaoting. 2024. ALYREF recruits ELAVL1 to promote colorectal tumorigenesis via facilitating RNA m5C recognition and nuclear export. In NPJ precision oncology, 8, 243. doi:10.1038/s41698-024-00737-0. https://pubmed.ncbi.nlm.nih.gov/39455812/

3. Madhukar, Geet, Subbarao, Naidu. 2023. Potential inhibitors of RPS6KB2 and NRF2 in head and neck squamous cell carcinoma. In Journal of biomolecular structure & dynamics, 42, 1875-1900. doi:10.1080/07391102.2023.2205946. https://pubmed.ncbi.nlm.nih.gov/37160694/

4. Ma, Qiang, Yang, Yipin, Chen, Shuwen, Gong, Peng, Hao, Jiqing. 2024. Ribosomal protein S6 kinase 2 (RPS6KB2) is a potential immunotherapeutic target for cancer that upregulates proinflammatory cytokines. In Molecular biology reports, 51, 229. doi:10.1007/s11033-023-09134-5. https://pubmed.ncbi.nlm.nih.gov/38281249/

5. Awah, Chidiebere U, Winter, Jan, Mazdoom, Claudiane M, Ogunwobi, Olorunseun O. 2021. NSUN6, an RNA methyltransferase of 5-mC controls glioblastoma response to temozolomide (TMZ) via NELFB and RPS6KB2 interaction. In Cancer biology & therapy, 22, 587-597. doi:10.1080/15384047.2021.1990631. https://pubmed.ncbi.nlm.nih.gov/34705606/

6. Slattery, Martha L, Lundgreen, Abbie, Herrick, Jennifer S, Wolff, Roger K. 2010. Genetic variation in RPS6KA1, RPS6KA2, RPS6KB1, RPS6KB2, and PDK1 and risk of colon or rectal cancer. In Mutation research, 706, 13-20. doi:10.1016/j.mrfmmm.2010.10.005. https://pubmed.ncbi.nlm.nih.gov/21035469/

7. Ilozumba, Mmadili N, Yao, Song, Llanos, Adana A M, Ambrosone, Christine B, Cheng, Ting-Yuan David. 2022. mTOR pathway gene expression in association with race and clinicopathological characteristics in Black and White breast cancer patients. In Discover oncology, 13, 34. doi:10.1007/s12672-022-00497-y. https://pubmed.ncbi.nlm.nih.gov/35608730/

8. Liu, Yang, Wei, Min, Guo, Hua, Zhao, Fazhen, Chen, Songlin. 2017. Locus Mapping, Molecular Cloning, and Expression Analysis of rps6kb2, a Novel Metamorphosis-Related Gene in Chinese Tongue Sole (Cynoglossus semilaevis). In Marine biotechnology (New York, N.Y.), 19, 497-516. doi:10.1007/s10126-017-9769-1. https://pubmed.ncbi.nlm.nih.gov/28779262/

9. Hao, Xiaoyan, Du, Yufeng, Qian, Li, Li, Dan, Liu, Xuejun. 2017. Upregulation of long noncoding RNA AP003419.16 predicts high risk of aging‑associated idiopathic pulmonary fibrosis. In Molecular medicine reports, 16, 8085-8091. doi:10.3892/mmr.2017.7607. https://pubmed.ncbi.nlm.nih.gov/28944926/