@article { author = {Liu, Guochao and Li, Tao and Ma, Lifeng and Wang, Jianlong and Yin, Zhaoqiang}, title = {MiR-582 Down-Regulates Lissencephaly-1 (LIS1) via P-Akt and MMP-2 to Inhibit Cholangiocarcinoma Cell Proliferation and Invasion}, journal = {Iranian Journal of Biotechnology}, volume = {20}, number = {4}, pages = {61-74}, year = {2022}, publisher = {National Institute of Genetic Engineering and Biotechnology of Iran}, issn = {1728-3043}, eissn = {2322-2921}, doi = {10.30498/ijb.2022.301092.3136}, abstract = {Background:Cholangiocarcinoma is a primary malignant tumor, and its progression involves oncogene activation, the absence of tumor suppressor gene, abnormal signaling pathways and miRNA expression. MiRNAs are abnormally expressed in many types of tumors.Objective:This study aims to observe the effects of miR-582 on cholangiocarcinoma cell proliferation, S-phase arrest, migration and invasion and to analyze the regulation of miR-582 on LIS1 to clarify the real role of miR-582 in cholangiocarcinoma development.Materials and Methods: TCGA database of cholangiocarcinoma samples was analyzed. Dual fluorescence reporter and TargetScan were conducted to confirm whether LIS1 was the target gene of miR-582. Effects of miR-582 and LIS1 on HCC-9810 cell proliferation, S-phase cell ratio, migration and invasion were determined by CCK-8, Flow cytometry and Transwell, respectively, whereas the function of miR-582 on MMP-2 and P-Akt expression was identified by Western blotting. Nude mice xenograft model of cholangiocarcinoma was established to detect what miR-582 did for tumor growth.Results:TCGA showed that miR-582 was lowly expressed and LIS1 was highly expressed in tumor tissues compared with adjacent tissues. MiR-582 targeted LIS1 to inhibit MMP-2 and p-AKT expression. Transfection of miR-582 mimics could suppress HCC-9810 cell proliferation, S-stage arrest, migration and invasion, while LIS1 worked oppositely. MiR-582 inhibitors promoted cell biological behavior, whereas LIS1 siRNA was opposite. In nude mice xenograft model, miR-582 overexpression inhibited tumor growth.Conclusions:It implies that miR-582 could negatively regulate LIS1 to inhibit MMP-2 and P-Akt expression, thus suppressing cell invasion and proliferation in cholangiocarcinoma.}, keywords = {cholangiocarcinoma,LIS1,MMP-2,miR-582,p-AKT}, url = {https://www.ijbiotech.com/article_157962.html}, eprint = {https://www.ijbiotech.com/article_157962_5e71bb1f2aa2470fb3f924689412a27c.pdf} }