The insulin-like growth factor (IGF)-axis has been paradigmatically involved in hepatocellular carcinoma (HCC) tumor initiation, progression and drug resistance. Consequently, members of the IGF-axis and most importantly, IGF-1 receptor (IGF-1R) have been considered as intriguing targets for HCC therapy. Few miRNAs have been recently reported to be associated with IGF-1R regulation. The present study aimed to investigate the role of microRNA (miRNA/miR)-486-5p in the regulation of IGF-1R and its downstream signaling cascades. miR-486-5p was markedly downregulated in hepatitis C virus-induced HCC tissues and Huh-7 cells. Forcing the expression of miR-486-5p in Huh-7 cells resulted in the repression of IGF-1R, mammalian target of rapamycin (mTOR), signal transducer and activator of transcription 3 (STAT3) and c-Myc mRNA levels. Ectopic expression of miR-486-5p in Huh-7 cells markedly repressed cellular viability, proliferation, migration and clonogenicity in a similar pattern to IGF-1R small interfering RNAs, and were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, BrdU incorporation, wound healing and colony forming assays, respectively. Overall, the study findings demonstrated that miR-486-5p acts as a tumor suppressor in HCC through the repression of essential members of the IGF-axis, including IGF-1R and its downstream mediators mTOR, STAT3 and c-Myc.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5038225 | PMC |
| http://dx.doi.org/10.3892/ol.2016.4914 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The signaling landscape of insulin-like growth factor 1.
J Biol Chem
December 2024
Achucarro Basque Center for Neuroscience, Leioa, Spain; CIBERNED, Madrid, Spain; Ikerbasque Science Foundation, Bilbao, Spain. Electronic address:
The sheer amplitude of biological actions of insulin-like growth factor I (IGF-1) affecting all types of cells in all tissues suggests a vast signaling landscape for this ubiquitous humoral signal. While the canonical signaling pathways primarily involve the Ras/MAPK and PI3K/AKT cascades, the evolutionary conservation of insulin-like peptides (ILPs) and their pathways hints at the potential for novel functions to emerge over time. Indeed, the evolutionary trajectory of ILPs opens the possibility of either novel functions for these two pathways, novel downstream routes, or both.
View Article and Find Full Text PDFDirect and indirect modulation of STAT3/CSE/HS axis in triple negative breast cancer by non-coding RNAs: MALAT-1 lncRNA, miR-486-5p and miR-30a-5p.
Pathol Res Pract
January 2025
Biochemistry Department, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo, Egypt. Electronic address:
Recently, our research group reported an upregulated expression profile of cystathionine γ-lyase (CSE) and cystathionine β-synthase (CBS), key enzymes involved in hydrogen sulfide (HS) production, in triple-negative breast cancer (TNBC) patients. However, the regulatory mechanisms underlying such altered expression patterns are not yet fully understood. In this study, we focused on the role of the STAT3/CSE/HS axis and the potential involvement of non-coding RNAs (ncRNAs), including long and short ncRNAs, in modulating this pivotal pathway.
View Article and Find Full Text PDFAdvances of IGF-1R inhibitors in Graves' ophthalmopathy.
Int Ophthalmol
November 2024
Department of Ophthalmology, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, Guangdong, China.
Article Synopsis
- Graves' ophthalmopathy, often seen in Graves' disease, primarily affects the eyes and is usually treated with glucocorticoids, though these can have side effects and don't change disease progression.
- * The IGF-1R (insulin-like growth factor-I receptor) plays a key role in the development of Graves' ophthalmopathy by influencing immune responses and protein production.
- * Teprotumumab, an antibody targeting IGF-1R, has shown in clinical trials to be more effective than placebo in reducing eye bulging (proptosis) and may help patients whose condition worsens after stopping steroid treatment.
SN promote retinal pathological neovascularization through activation of EGFR, IR and IGF-1R.
Exp Eye Res
January 2025
Department of Ophthalmology, The People's Hospital of Guangxi Zhuang Autonomous Region & Guangxi Key Laboratory of Eye Health & Guangxi Health Commission Key Laboratory of Ophthalmology and Related Systemic Diseases Artificial Intelligence Screening Technology &Institute of Ophthalmic Diseases, Guangxi Academy of Medical Sciences, Nanning, 530021, China. Electronic address:
Article Synopsis
- Secretoneurin (SN) is a neuropeptide linked to the neuroendocrine system and plays a role in retinal health and pathology.
- The study found that overexpression of secretogranin II (SgII) in a mouse model of Oxygen-Induced Retinopathy (OIR) resulted in increased pathological neovascularization, while reducing SgII helped alleviate this condition without affecting normal retinal development.
- The research revealed that SN promotes angiogenesis in the eye by activating specific receptors (EGFR, IR, IGF-1R) and triggering the PI3K-AKT-mTOR signaling pathway.
Small molecule modulation of insulin receptor-insulin like growth factor-1 receptor heterodimers in human endothelial cells.
Mol Cell Endocrinol
December 2024
School of Biomedical Sciences, Faculty of Biological Sciences & Astbury Centre, University of Leeds, United Kingdom.
Objectives: The insulin receptor (IR) and insulin like growth factor-1 receptor (IGF-1R) are heterodimers consisting of two extracellular α-subunits and two transmembrane β -subunits. Insulin αβ and insulin like growth factor-1 αβ hemi-receptors can heterodimerize to form hybrids composed of one IR αβ and one IGF-1R αβ. The function of hybrids in the endothelium is unclear.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!