miRNA-target network reveals miR-124as a key miRNA contributing to clear cell renal cell carcinoma aggressive behaviour by targeting CAV1 and FLOT1

Henriett Butz, Peter M. Szabó, Heba W Z Khella, Roy Nofech-Mozes, A. Patócs, George M. Yousef

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Clear cell renal cell carcinoma (ccRCC) is an aggressive tumor with frequent metastatic rate and poor survival. Integrated analyses allow understanding the interplay between different levels of molecular alterations. We integrated miRNA and gene expression data from 458 ccRCC and 254 normal kidney specimens to construct a miRNA-target interaction network. We identified the downregulated miR-124-3p, -30a-5p and -200c-3p as the most influential miRNAs in RCC pathogenesis.miR-124-3p and miR-200c-3p expression showed association with patient survival, miR-30a-5p was downregulated in metastases compared to primary tumors. We used an independent set of 87 matched samples for validation. We confirmed the functional impact of these miRNAs by in vitro assays. Restoration of these miRNAs reduced migration, invasion and proliferation. miR-124-3p decreased the S phase of cell cycle, as well. We compared transcriptome profiling before and after miRNA overexpression, and validated CAV1 and FLOT1 as miR-124-3p targets. Patients with higher CAV1 and FLOT1 had lower miR-124-3p expression and shorter overall survival. We hypothesize that these three miRNAs are fundamental contributing to ccRCC aggressive/metastatic behavior; and miR-124-3p especially has a key role through regulating CAV1 and FLOT1 expression. Restoration of the levels of these miRNAs could be considered as a potential therapeutic strategy for ccRCC.

Original languageEnglish
Pages (from-to)12543-12557
Number of pages15
JournalOncotarget
Volume6
Issue number14
Publication statusPublished - 2015

Fingerprint

MicroRNAs
Renal Cell Carcinoma
Down-Regulation
Survival
Gene Expression Profiling
S Phase
Neoplasms
Cell Cycle
Survival Rate
Neoplasm Metastasis
Kidney
Gene Expression

Keywords

  • CAV1
  • FLOT1
  • Integrated analysis
  • MiR-124-3p
  • Renal cell carcinoma

ASJC Scopus subject areas

  • Oncology

Cite this

miRNA-target network reveals miR-124as a key miRNA contributing to clear cell renal cell carcinoma aggressive behaviour by targeting CAV1 and FLOT1. / Butz, Henriett; Szabó, Peter M.; Khella, Heba W Z; Nofech-Mozes, Roy; Patócs, A.; Yousef, George M.

In: Oncotarget, Vol. 6, No. 14, 2015, p. 12543-12557.

Research output: Contribution to journalArticle

Butz, Henriett ; Szabó, Peter M. ; Khella, Heba W Z ; Nofech-Mozes, Roy ; Patócs, A. ; Yousef, George M. / miRNA-target network reveals miR-124as a key miRNA contributing to clear cell renal cell carcinoma aggressive behaviour by targeting CAV1 and FLOT1. In: Oncotarget. 2015 ; Vol. 6, No. 14. pp. 12543-12557.
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