title: Transcriptional activation of the IGF-II/IGF-1R axis and inhibition of IGFBP-3 by miR-155 in hepatocellular carcinoma.
abstract: Hepatocellular carcinoma (HCC) is characterized by the aberrant expression of a number of genes that govern crucial signaling pathways. The insulin-like growth factor (IGF) axis is important in this context, and the precise regulation of expression of members of this axis is known to be lost in HCC. miR-155 is a well-established oncogene in numerous types of cancer. However, to the best of our knowledge, its effect on the regulation of the IGF axis has not been investigated to date. The present study aimed to elucidate the interactions between miR-155 and key components of the IGF axis, in addition to examining its effect on HCC development. Reverse transcription-quantitative polymerase chain reaction was used to measure the expression of miR-155 in HCC and cirrhotic tissues, in addition to HCC cell lines. Furthermore, the effect of the induction of miR-155 expression on the expression of three members of the IGF axis [IGF II, IGF type-1 receptor (IGF-1R) and IGF-binding protein 3 (IGFBP-3)], was analyzed. Finally, the effect of miR-155 on HCC cell proliferation, migration and clonogenicity was also examined. Quantification of the expression of miR-155 demonstrated that it is upregulated in HCC. Induction of the expression of miR-155 in HCC cell lines led to the upregulation of IGF-II and IGF-IR, and the downregulation of IGFBP-3. In addition, the proliferation, migration and clonogenicity of HCC was increased following induction of miR-155 expression. miR-155 is an oncomiR, which upregulates the oncogenes, IGF-II and IGF-IR, and downregulates the tumor suppressor, IGFBP-3, thereby resulting in increased HCC cell carcinogenicity. Therefore, miR-155 may be a therapeutic target in HCC.
authors.affiliation: The Molecular Pathology Research Group, Department of Pharmacology and Toxicology, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo 11432, Egypt.
authors.forename: Hend M
authors.initials: HM
authors.lastname: El Tayebi
authors.affiliation: The Molecular Pathology Research Group, Department of Pharmacology and Toxicology, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo 11432, Egypt.
authors.forename: Amr A
authors.initials: AA
authors.lastname: Waly
authors.affiliation: The Molecular Pathology Research Group, Department of Pharmacology and Toxicology, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo 11432, Egypt.
authors.forename: Reem A
authors.initials: RA
authors.lastname: Assal
authors.affiliation: Department of General Surgery, Faculty of Medicine, Cairo University, Cairo 11835, Egypt.
authors.forename: Karim A
authors.initials: KA
authors.lastname: Hosny
authors.affiliation: Department of Endemic Medicine and Hepatology, Faculty of Medicine, Cairo University, Cairo 11835, Egypt.
authors.forename: Gamal
authors.initials: G
authors.lastname: Esmat
authors.affiliation: The Molecular Pathology Research Group, Department of Pharmacology and Toxicology, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo 11432, Egypt.
authors.forename: Ahmed I
authors.initials: AI
authors.lastname: Abdelaziz
keywords: hepatocellular carcinoma; insulin-like growth factor II; insulin-like growth factor type-1 receptor; insulin-like growth factor-binding protein 3; microRNA-155