miR-210 is a target of hypoxia-inducible factors 1 and 2 in renal cancer, regulates ISCU and correlates with good prognosis.

Abstract

BACKGROUND:

Clear cell renal cancer frequently harbours von Hippel-Lindau (VHL) gene mutations, leading to stabilisation of the hypoxia-inducible factors (HIFs) and expression of their target genes. We investigated HIF-1 and HIF-2 in the regulation of microRNA-210 (miR-210), and its clinical relevance in renal tumours.

METHODS:

RCC4 and 786-O renal cancer cell lines transfected with either an empty vector or functional VHL and incubated in normoxia or hypoxia were examined for miR-210 expression. Hypoxia-inducible factor siRNAs were used to examine their regulation of miR-210. Seventy-one clear cell renal tumours were sequenced for VHL mutations. Expression of miR-210, VHL, CA9, ISCU and Ki-67 were determined by immunohistochemistry and qRT-PCR.

RESULTS:

In addition to HIF-1 regulating miR-210 in renal cancer, HIF-2 can regulate this microRNA in the absence of HIF-1. MicroRNA-210 is upregulated in renal cancer compared with normal renal cortex tissue. MicroRNA-210 correlates negatively with its gene target ISCU at the protein and mRNA level. MicroRNA-210 correlated with positive outcome variables and negatively with Ki-67.

CONCLUSION:

We provide further evidence of miR-210 activity in vivo, and show that high miR-210 expression is associated with better clinico-pathological prognostic factors.

• Authors: R I McCormick, C Blick, J Ragoussis, J Schoedel, D R Mole, A C Young, P J Selby, R E Banks, A L Harris
• Journal: British journal of cancer (Br J Cancer) Vol. 108 Issue 5 Pg. 1133-42 (Mar 19 2013) ISSN: 1532-1827 [Electronic] England
• PMID: 23449350 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Basic Helix-Loop-Helix Transcription Factors
• Hypoxia-Inducible Factor 1
• ISCU protein, human
• Iron-Sulfur Proteins
• MIRN210 microRNA, human
• MicroRNAs
• endothelial PAS domain-containing protein 1
• Von Hippel-Lindau Tumor Suppressor Protein

Topics

• Adult
• Aged
• Aged, 80 and over
• Basic Helix-Loop-Helix Transcription Factors (metabolism)
• Carcinoma, Renal Cell (genetics, metabolism)
• Cell Line, Tumor
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Hypoxia-Inducible Factor 1 (metabolism)
• Iron-Sulfur Proteins (metabolism)
• Kidney Neoplasms (genetics, metabolism)
• Male
• MicroRNAs (genetics)
• Middle Aged
• Mutation
• Prognosis
• Up-Regulation
• Von Hippel-Lindau Tumor Suppressor Protein (genetics)