A pleiotropic effect of the single clustered hepatic metastamiRs miR-96-5p and miR-182-5p on insulin-like growth factor II, insulin-like growth factor-1 receptor and insulin-like growth factor-binding protein-3 in hepatocellular carcinoma.
MicroRNAs (miRs) have a major role in the pathogenesis of hepatocellular carcinoma (HCC). As the insulin-like growth factor (IGF) axis is a highly tumorigenic pathway in HCC, the present study attempted to target it with miRs. Potential targeting of crucial members of the IGF axis by miRNAs at the 3'-untranslated region (3'-UTR) was predicted using bioinformatic tools, such as microrna.org, Diana lab and Targetscan, while 5'-UTR targeting was predicted using bibiserv software. Expression profiling of obtained miRNAs was performed using quantitative polymerase chain reaction (qPCR) in 22 non-metastatic HCC biopsy samples and 10 healthy tissues. To investigate the impact of miRNAs on their potential downstream targets, transfection of miRNAs was performed in HuH-7 cells and the targets' expression was quantified using qPCR. Transcripts of insulin-like growth factor-1 receptor (IGF-1R), insulin-like growth factor binding protein-3 (IGFBP-3) and IGF-II were found to be potentially targeted at the 5'-UTR and 3'-UTR regions by the single clustered hepatic metastamiRs miR-96-5p and miR-182-5p. The two miRNAs showed a similar expression pattern in HCC tissues compared to those in healthy tissues. Forced expression of miR-96-5p and miR-182-5p in the HCC cell line HuH-7 had inducing effects on IGFBP-3 and IGF-II transcripts. Of note, the two miRs had differential effects on IGF-1R, where miR-96-5p induced IGF-1R mRNA expression and miR-182-5p inhibited its expression. The present study revealed the pleiotropic impact of the single clustered hepatic metastamiRs miR-96-5p and miR-182-5p on IGF-1R, and an inducing effect on IGF-II and IGFBP-3 in hepatocellular carcinoma.
The Molecular Pathology Research Group, Department of Pharmacology and Toxicology, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo 11835, Egypt.
Reem Amr
RA
Assal
The Molecular Pathology Research Group, Department of Pharmacology and Toxicology, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo 11835, Egypt.
Hend Mohamed
HM
El Tayebi
Department of General Surgery, Faculty of Medicine, Cairo University, Cairo 11559, Egypt.
Karim Adel
KA
Hosny
Department of Endemic Medicine and Hepatology, Cairo University, Cairo 11559, Egypt.
Gamal
G
Esmat
The Molecular Pathology Research Group, Department of Pharmacology and Toxicology, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo 11835, Egypt.
Ahmed Ihab
AI
Abdelaziz
D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000096:biosynthesis* / Q000235:genetics; D007335:Insulin-Like Growth Factor II / Q000096:biosynthesis* / Q000235:genetics; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics*; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis* / Q000235:genetics; D014162:Transfection
C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; C541492:MIRN96 microRNA, human; D035683:MicroRNAs; C538984:Mirn182 microRNA, human; D007335:Insulin-Like Growth Factor II; D017526:Receptor, IGF Type 1