caa a22 4500 606235450 CHVBK 20210128101242.0 cr unu---uuuuu 210128e20151001xx s 000 0 eng 10.1007/s11010-015-2506-z doi (NATIONALLICENCE)springer-10.1007/s11010-015-2506-z Down-regulated miR-28-5p in human hepatocellular carcinoma correlated with tumor proliferation and migration by targeting insulin-like growth factor-1 (IGF-1) [Elektronische Daten] [Xiaomin Shi, Fei Teng] Hepatocellular carcinoma (HCC) is a rapidly progressing, incurable cancer that frequently spreads to portal vein and lung. New insights are needed to identify therapeutic targets to prevent or retard HCC metastatic progression. Because microRNAs (miRNA) often act as tumor regulators, we investigated their role in preclinical models of HCC. Here we found miR-28-5p is a liver-relevant anti-proliferative miRNA whose expression, functions, and mechanisms were analyzed in human hepatoma cells, HepG2 and Huh7. Interestingly, when evaluating the specific targets of miR-28-5p, we found that ectopic miR-28-5p expression down-regulates insulin-like growth factor 1 (IGF1) protein and that the expression of miR-28-5p correlates negatively with IGF1 protein in HCC cells. Luciferase report in HCC cells expressing miR-28-5p suggests that miR-28-5p reduces luciferase activity by targeting the 3′-UTR of IGF1 mRNA. Additionally, we show that the selective inhibition of either the PI3K/AKT pathway prior to miR-28-5p stimulation prevents the expression of previously described tumor suppressor miRNAs that are family and cluster specific. Together, our results defined miR-28-5p as a critical regulator of IGF1 mRNA translation function, down-regulated miR-28-5p in HCC was associated with tumor growth through PI3K/AKT pathway by targeting IGF1. miR-28-5p-IGF1-PI3K/AKT pathway may play an important role in the development of HCC. Springer Science+Business Media New York, 2015 Hepatocellular carcinoma nationallicence miRNA-28-5p nationallicence IGF1 nationallicence PI3K/AKT nationallicence Shi Xiaomin Liver Surgery Department, Shanghai Changzheng Hospital, 415 Fengyang Road, 200003, Shanghai, China aut Teng Fei Liver Surgery Department, Shanghai Changzheng Hospital, 415 Fengyang Road, 200003, Shanghai, China aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 408/1-2(2015-10-01), 283-293 0300-8177 408:1-2<283 2015 408 11010 https://doi.org/10.1007/s11010-015-2506-z text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-015-2506-z text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Shi Xiaomin Liver Surgery Department, Shanghai Changzheng Hospital, 415 Fengyang Road, 200003, Shanghai, China aut NATIONALLICENCE 700 1- Teng Fei Liver Surgery Department, Shanghai Changzheng Hospital, 415 Fengyang Road, 200003, Shanghai, China aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 408/1-2(2015-10-01), 283-293 0300-8177 408:1-2<283 2015 408 11010