Malat1-KO Mouse

Malat1, short for Metastasis-associated lung adenocarcinoma transcript-1, is a highly conserved nucleus-restricted long non-coding RNA (lncRNA). It regulates genes at transcriptional and post-transcriptional levels and is associated with multiple signaling pathways such as MAPK/ERK, PI3K/AKT, β-catenin/Wnt, Hippo, VEGF, YAP etc. Malat1 is important in numerous diseases, especially cancer, and has potential as a biomarker for cancer diagnosis and prognosis, as well as a therapeutic target [1,2,3,6,7].

In mouse models, targeted knockdown of Malat1 in endothelial cells exacerbated oxidative stress, attenuated angiogenesis and microvascular perfusion, and decreased cardiac function in myocardial infarction (MI) mice. This indicates that Malat1 is involved in repairing cardiac microvascular dysfunction after MI. Specifically, it acts as a competing endogenous RNA for miR-26b-5p and forms a signaling axis with Mfn1 to regulate mitochondrial dynamics and endothelial functions [4]. In another study, knockdown of Malat1 in chondrocytes treated with IL-1β inhibited cell proliferation, promoted apoptosis, and increased extracellular matrix degradation, suggesting its role in osteoarthritis progression [5].

In conclusion, Malat1 plays crucial roles in various biological processes and disease conditions. Mouse models, especially those with Malat1 knockdown, have revealed its significance in cardiac microvascular function post-MI and osteoarthritis. These findings contribute to understanding its function in specific disease areas, highlighting its potential as a therapeutic target and biomarker in related diseases.

References:

1. Xu, Wen-Wen, Jin, Jin, Wu, Xiao-Yu, Ren, Qing-Ling, Farzaneh, Maryam. 2022. MALAT1-related signaling pathways in colorectal cancer. In Cancer cell international, 22, 126. doi:10.1186/s12935-022-02540-y. https://pubmed.ncbi.nlm.nih.gov/35305641/

2. Goyal, Bela, Yadav, Shashi Ranjan Mani, Awasthee, Nikee, Kunnumakkara, Ajaikumar B, Gupta, Subash Chandra. 2021. Diagnostic, prognostic, and therapeutic significance of long non-coding RNA MALAT1 in cancer. In Biochimica et biophysica acta. Reviews on cancer, 1875, 188502. doi:10.1016/j.bbcan.2021.188502. https://pubmed.ncbi.nlm.nih.gov/33428963/

3. Arun, Gayatri, Aggarwal, Disha, Spector, David L. 2020. MALAT1 Long Non-Coding RNA: Functional Implications. In Non-coding RNA, 6, . doi:10.3390/ncrna6020022. https://pubmed.ncbi.nlm.nih.gov/32503170/

4. Chen, Yuqiong, Li, Su, Zhang, Yan, Lu, Yao, Jia, Dalin. 2021. The lncRNA Malat1 regulates microvascular function after myocardial infarction in mice via miR-26b-5p/Mfn1 axis-mediated mitochondrial dynamics. In Redox biology, 41, 101910. doi:10.1016/j.redox.2021.101910. https://pubmed.ncbi.nlm.nih.gov/33667993/

5. Zhang, Ying, Wang, Fuyou, Chen, Guangxing, He, Rui, Yang, Liu. 2019. LncRNA MALAT1 promotes osteoarthritis by modulating miR-150-5p/AKT3 axis. In Cell & bioscience, 9, 54. doi:10.1186/s13578-019-0302-2. https://pubmed.ncbi.nlm.nih.gov/31304004/

6. Li, Zhi-Xing, Zhu, Qiong-Ni, Zhang, Hai-Bo, Wang, Guo, Zhu, Yuan-Shan. 2018. MALAT1: a potential biomarker in cancer. In Cancer management and research, 10, 6757-6768. doi:10.2147/CMAR.S169406. https://pubmed.ncbi.nlm.nih.gov/30584369/

7. Zhao, Miaomiao, Wang, Songpo, Li, Qi, Guo, Piaoting, Liu, Xiaowei. 2018. MALAT1: A long non-coding RNA highly associated with human cancers. In Oncology letters, 16, 19-26. doi:10.3892/ol.2018.8613. https://pubmed.ncbi.nlm.nih.gov/29928382/