MicroRNA profile indicates downregulation of the TGFβ pathway in sporadic non-functioning pituitary adenomas

Henriett Butz, István Likó, S. Czirják, P. Igaz, Márta Korbonits, K. Rácz, A. Patócs

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

MicroRNAs (miRs) are small, 16-29 nucleotide long, non-coding RNA molecules which regulate the stability or translational efficiency of targeted mRNAs via RNA interference. MiRs participate in the control of cell proliferation, cell differentiation, signal transduction, cell death, and they play a role in carcinogenesis. The aims of our study were to analyse the expression profile of miRs in sporadic clinically non-functioning pituitary adenomas (NFPA) and in normal pituitary tissues, and to identify biological pathways altered in these pituitary tumors. MiR expression profiles of 12 pituitary tissue specimens (8 NFPA and 4 normal pituitary tissues) were determined using miR array based on quantitative real-time PCR with 678 different primers. Five overexpressed miRs and mRNA expression of Smads (Smad1-9), MEG and DLK1 genes were evaluated with individual Taqman assays in 10 NFPA and 10 normal pituitary tissues. Pathway analysis was performed by the DIANA-mirPath tool. Complex bioinformatical analysis by multiple algorithms and association studies between miRs, Smad3 and tumor size was performed. Of the 457 miRs expressed in both NFPA and normal tissues, 162 were significantly under- or overexpressed in NFPA compared to normal pituitary tissues Expression of Smad3, Smad6, Smad9, MEG and DLK1 was significantly lower in NFPA than in normal tissues. Pathway analysis together with in silico target prediction analysis indicated possible downregulation of the TGFβ signaling pathway in NFPA by a specific subset of miRs. Five miRs predicted to target Smad3 (miR-135a, miR-140-5p, miR-582-3p, miR-582-5p and miR-938) were overexpressed. Correlation was observed between the expression of seven overexpressed miRs and tumor size. Downregulation of the TGFβ signaling through Smad3 via miRs may have a possible role in the complex regulation of signaling pathways involved in the tumorigenesis process of NFPA.

Original languageEnglish
Pages (from-to)112-124
Number of pages13
JournalPituitary
Volume14
Issue number2
DOIs
Publication statusPublished - Jun 2011

Fingerprint

Pituitary Neoplasms
MicroRNAs
Down-Regulation
Carcinogenesis
Long Noncoding RNA
Messenger RNA
RNA Interference
Computer Simulation
Real-Time Polymerase Chain Reaction
Cell Differentiation
Signal Transduction
Neoplasms
Cell Death
Nucleotides
Cell Proliferation

Keywords

  • Expression profile
  • miRNA
  • Pathway analysis
  • Pituitary adenoma
  • Smad3
  • TGFβ

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

MicroRNA profile indicates downregulation of the TGFβ pathway in sporadic non-functioning pituitary adenomas. / Butz, Henriett; Likó, István; Czirják, S.; Igaz, P.; Korbonits, Márta; Rácz, K.; Patócs, A.

In: Pituitary, Vol. 14, No. 2, 06.2011, p. 112-124.

Research output: Contribution to journalArticle

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