Mir494-KO Mouse

Mir494, a microRNA, is involved in regulating diverse biological processes. It has been associated with pathways like the phosphatase and tensin homolog/phosphoinositide 3-kinase (PTEN/PI3K) axis, and signaling pathways such as transforming growth factor-β (TGF-β), WNT, and Janus kinase (JAK)-signal transducer and activator of transcription (STAT) [4]. Mir494 can function as a tumor suppressor or an oncogene, and due to its high stability in body fluids, it has the potential to be a non-invasive diagnostic tumor marker [4].

In esophageal squamous cell carcinoma (ESCC), miR494 (miR-494-3p) is up-regulated and positively associated with T stage and lymph node metastasis. It promotes radioresistance and metastasis by targeting cullin 3 (CUL3), which is transcriptionally regulated by JunD. The JunD-miR494-CUL3 axis facilitates epithelial-mesenchymal transition (EMT) and restrains programmed cell death 1 ligand 1 (PD-L1) degradation, highlighting its role in ESCC progression [1]. In renal cancer cells, MIR494 reduces cell survival, accompanied by increased lipid droplet formation (in a LC3B-dependent manner) and mitochondrial changes [2]. In acute kidney injury, miR-494 may bind to the 3'-untranslated region of its target genes to regulate inflammation, programmed cell death, and cell cycle, indicating its therapeutic potential [3]. In ischemic stroke, exosomal circBBS2 inhibits ferroptosis by targeting miR-494 to activate SLC7A11 signaling [5]. In hepatocellular carcinoma (HCC), miR-494 induces a metabolic shift toward a glycolytic phenotype through G6pc targeting and HIF-1A pathway activation, and is associated with sorafenib resistance [6].

In conclusion, Mir494 plays crucial roles in multiple biological processes and disease conditions. Its functions in cancer progression, cell survival, and metabolic regulation have been demonstrated through various studies. In particular, in diseases like ESCC, renal cancer, acute kidney injury, ischemic stroke, and HCC, Mir494 shows potential as a prognostic predictor and therapeutic target, highlighting the importance of further research on Mir494 for understanding disease mechanisms and developing new treatments.

References:

1. Li, Xin, Cong, Ji, Zhou, Xuantong, Liu, Zhihua, Luo, Aiping. 2024. JunD-miR494-CUL3 axis promotes radioresistance and metastasis by facilitating EMT and restraining PD-L1 degradation in esophageal squamous cell carcinoma. In Cancer letters, 587, 216731. doi:10.1016/j.canlet.2024.216731. https://pubmed.ncbi.nlm.nih.gov/38369005/

2. Dutta, Punashi, Haller, Edward, Sharp, Arielle, Nanjundan, Meera. 2016. MIR494 reduces renal cancer cell survival coinciding with increased lipid droplets and mitochondrial changes. In BMC cancer, 16, 33. doi:10.1186/s12885-016-2053-3. https://pubmed.ncbi.nlm.nih.gov/26794413/

3. Ren, Gui-Ling, Zhu, Jie, Li, Jun, Meng, Xiao-Ming. 2018. Noncoding RNAs in acute kidney injury. In Journal of cellular physiology, 234, 2266-2276. doi:10.1002/jcp.27203. https://pubmed.ncbi.nlm.nih.gov/30146769/

4. Maharati, Amirhosein, Akhlaghipour, Iman, Taghehchian, Negin, Farshchian Yazdi, Zahra, Moghbeli, Meysam. 2023. Role of microRNA-494 in tumor progression. In American journal of translational research, 15, 6342-6361. doi:. https://pubmed.ncbi.nlm.nih.gov/38074823/

5. Hong, Ting, Zhao, Tingting, He, Wei, Liu, Yunhai, Feng, Jie. . Exosomal circBBS2 inhibits ferroptosis by targeting miR-494 to activate SLC7A11 signaling in ischemic stroke. In FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 37, e23152. doi:10.1096/fj.202300317RRR. https://pubmed.ncbi.nlm.nih.gov/37603538/

6. Bergamini, Christian, Leoni, Ilaria, Rizzardi, Nicola, Gramantieri, Laura, Fornari, Francesca. 2023. MiR-494 induces metabolic changes through G6pc targeting and modulates sorafenib response in hepatocellular carcinoma. In Journal of experimental & clinical cancer research : CR, 42, 145. doi:10.1186/s13046-023-02718-w. https://pubmed.ncbi.nlm.nih.gov/37301960/