Mir200c-KO Mouse

Mir200c is a microRNA that has been implicated in various biological functions and disease-related processes. It plays roles in post-transcriptional regulation, affecting the expression of target genes involved in multiple pathways, which are crucial for maintaining normal cellular functions and are associated with diseases such as cancer and intestinal inflammation [1-10].

In intestinal inflammation, IL1B up-regulates Mir200C-3p, which degrades occludin mRNA, increasing intestinal tight junction permeability. In mouse models, antagomiR-200C (an antagonist to MIR200C-3p) prevents the decrease in occludin in enterocytes and maintains the tight junction barrier [1]. In prostate cancer, over-expression of miR200c suppresses cell growth by targeting insulin receptor substrate 1 (IRS1) [2]. In colorectal cancer, miR200c can attenuate P-gp-mediated multidrug resistance (MDR) and metastasis by targeting the JNK2/c-Jun signaling pathway. In an orthotopic MDR colorectal cancer mouse model, over-expression of miR200c effectively inhibits tumor growth and metastasis [3].

In summary, Mir200c is involved in post-transcriptional regulation of multiple genes, affecting biological processes relevant to disease development. Studies using mouse models, such as those with modulation of Mir200c expression, have revealed its roles in intestinal inflammation, prostate cancer, and colorectal cancer, providing insights into potential therapeutic strategies for these diseases [1,2,3].

References:

1. Rawat, Manmeet, Nighot, Meghali, Al-Sadi, Rana, Koltun, Walter, Ma, Thomas Y. 2020. IL1B Increases Intestinal Tight Junction Permeability by Up-regulation of MIR200C-3p, Which Degrades Occludin mRNA. In Gastroenterology, 159, 1375-1389. doi:10.1053/j.gastro.2020.06.038. https://pubmed.ncbi.nlm.nih.gov/32569770/

2. Su, Wenjing, Xu, Miao, Chen, Xueqin, Huang, Lei, Zhou, Qiao. 2015. MiR200c targets IRS1 and suppresses prostate cancer cell growth. In The Prostate, 75, 855-62. doi:10.1002/pros.22968. https://pubmed.ncbi.nlm.nih.gov/25683382/

3. Sui, Hua, Cai, Guo-Xiang, Pan, Shu-Fang, Zhu, Hui-Rong, Li, Qi. 2014. miR200c attenuates P-gp-mediated MDR and metastasis by targeting JNK2/c-Jun signaling pathway in colorectal cancer. In Molecular cancer therapeutics, 13, 3137-51. doi:10.1158/1535-7163.MCT-14-0167. https://pubmed.ncbi.nlm.nih.gov/25205654/