Brix1-KO Mouse

BRIX1, also known as biogenesis of ribosomes BRX1, is a nucleolar protein critically involved in ribosome biogenesis. It facilitates pre-rRNA processing by supporting the formation of the PeBoW complex and is part of pathways related to ribosome assembly and biogenesis [1,2]. BRIX1 is also important in maintaining the homeostasis between ribosome biogenesis and p53 activation, and its abnormal expression may be associated with multiple biological processes and diseases.

Depletion of BRIX1 in cancer cells has shown significant effects. It induces nucleolar stress, which in turn activates p53 through RPL5 and RPL11, leading to the inhibition of tumor growth. Engineered exosomes loaded with siRNAs specific to BRIX1 can suppress the growth of colorectal cancer and enhance the efficacy of 5-FU chemotherapy in vivo [1]. In colorectal cancer, BRIX1 knockdown decreases rRNA levels, nascent RNA synthesis, glycolysis, and cell proliferation, while overexpression has the opposite effects. It also promotes ribosome synthesis and enhances glycolysis by selected translation of GLUT1 [2]. Additionally, in colorectal cancer patients, higher BRIX1 expression is positively correlated with tumor stage and serves as a risk factor for overall survival [3].

In conclusion, BRIX1 plays a crucial role in ribosome biogenesis and is involved in the progression of cancer, especially colorectal cancer. The use of gene-targeting methods such as siRNA-loaded exosomes targeting BRIX1 in in vivo studies shows potential as a cancer treatment strategy, highlighting the importance of understanding BRIX1 function for cancer therapy.

References:

1. Gan, Yu, Hao, Qian, Han, Tao, Chen, Jiaxiang, Zhou, Xiang. 2024. Targeting BRIX1 via Engineered Exosomes Induces Nucleolar Stress to Suppress Cancer Progression. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 11, e2407370. doi:10.1002/advs.202407370. https://pubmed.ncbi.nlm.nih.gov/39475053/

2. Jiang, Chunhui, Sun, Longci, Wen, Siyuan, Xu, Qing, Xue, Hanbing. . BRIX1 promotes ribosome synthesis and enhances glycolysis by selected translation of GLUT1 in colorectal cancer. In The journal of gene medicine, 26, e3632. doi:10.1002/jgm.3632. https://pubmed.ncbi.nlm.nih.gov/38282151/

3. Ge, Jianxin, Huang, Xiaoli, Wang, Ping, Lu, Cuihua. . Expression of biogenesis of ribosomes BRX1 is associated with malignant progression and prognosis in colorectal cancer. In Translational cancer research, 9, 5595-5602. doi:10.21037/tcr-20-2564. https://pubmed.ncbi.nlm.nih.gov/35117923/