MicroRNAs (miRNA) are non-coding molecules of small size (22 nucleotides) Their main role is the gene regulation at the post-transcriptional level… [606916]

MicroRNAs in
pituitary tumors

Kiraly Antonia Ema

Introduction
MicroRNAs (miRNA) are non-coding
molecules of small size (22 nucleotides)
Their main role is the gene regulation at
the post-transcriptional level
They are mostly located inside the cells of
plants, animals, some viruses
Some are extracellular: circulating miRNA

Cellular functions
Mainly gene regulation
Complementary to messengerRNAs
Imperfect match-up in animal organisms
Various mechanisms described

A. Zinovyev, N. Morozova, A. N. Gorban, A. Harel-Belan – Math ematical
modeling of microRNA-mediated mechanisms of translation

Detection and experimental
manipulation
Degrade easier than messengerRNAs
Quantification through modified RT-PCR +
quantitative PCT
Microarray
MicroRNAs sequencing
Available database for diseases:
miR2Disease

Cancer
Causality in many types of cancers
through miRNA dysregulation
Tumor suppressor or oncogene(oncomiR)
Many miRNA genes in cancer regions or
fragile sites
=> classification, diagnosis, treatment,
prognosis
miRNA mimics/antagonists

Pituitary adenomas
Aprox. 15% of intracranial tumors
Mainly benign, but important morbidity
through mass effect +/- hypopituitarism
Mostly sporadic, some familial cases
Can be functioning/nonfunctioning 
hormone hypersecretion
Micro-/macroadenomas  size

Pathogenesis
Unclear
Genetic factors , hormonal mechanisms,
growth factors
Microarray: genes involved in pituitary
tumorigenesis
Can analyze thousands of genes
simultaneously
Gene expression differences normal
pituitary vs. pituitary adenomas

Jiang X, Zhang X. The molecular pathogenesis of pituitary adenomas:
an update. Endocrinol Metab. 2013;28(4):245- 54.

Pathogenesis (2)
Complex involvement in tumorigenesis of
pituitary adenomas
Cell cycle arrest => inhibition of cell
growth
Apoptosis
Direct interaction with transcription factors

Zhao P, Hu W, Wang H, Yu S, Li C, Bai J, et al. Identification of
differentially expressed genes in pituitary adenomas by integrating
analysis of microarray data. Int J Endocrinol. 2015;2015:164087.

Zhao P, Hu W, Wang H, Yu S, Li C, Bai J, et al. Identification of
differentially expressed genes in pituitary adenomas by integrating
analysis of microarray data. Int J Endocrinol. 2015;2015:164087.

Pathogenesis (3)
Study that compared normal samples
with pituitary tumors
Entire micrRNA transcriptome analyzed
with microarray + RT-PCR
Many miRNAs expressed differently
between normal pituitary – adenomas
Predictive factor of miRNAs of adenomas
and histology type

Bottoni A, Zatelli MC, Ferracin M, Tagliati F, Piccin D, Vi gnali C, et al.
Identification of differentially expressed microRNAs by microarray: a
possible role for microRNA genes in pituitary adenomas. J Cell Physiol.
2007;210(2):370- 7.

Bottoni A, Zatelli MC, Ferracin M, Tagliati F, Piccin D, Vi gnali C, et al.
Identification of differentially expressed microRNAs by microarray: a
possible role for microRNA genes in pituitary adenomas. J Cell Physiol.
2007;210(2):370- 7.

Pathogenesis (4)
Study that investigated miR-106b + PTEN in
pituitary adenomas
Mir-106b up-regulation in tumor sample
PTEN down-regulation through PI3/AKT
pathway of signaling
=> Involvement of miR-106b in pituitary
adenoma proliferation and invasion
through targeting of PTEN directly

Zhou K, Zhang T, Fan Y, Serick, Du G, Wu P, et al. MicroRNA-106b
promotes pituitary tumor cell proliferation and invasion through
PI3K/AKT signaling pathway by targeting PTEN. Tumour Biol.
2016;37(10):13469- 77.

Summary
Molecular differences between
the normal pituitary tissue and
adenomas may lead to
identifying new therapeutic
agents via targeted therapy

References
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Bottoni A, Zatelli MC, Ferracin M, Tagliati F, Piccin D, Vignali C, et al. Identification of
differentially expressed microRNAs by microarray: a possible role for microRNA genes in
pituitary adenomas. J Cell Physiol. 2007;210(2):370- 7.
Zhao P, Hu W, Wang H, Yu S, Li C, Bai J, et al. Identification of differentially expressed genes
in pituitary adenomas by integrating analysis of microarray data. Int J Endocrinol .
2015;2015:164087.
Zhou K, Zhang T, Fan Y, Serick, Du G, Wu P, et al. MicroRNA-106b promotes pituitary tumor
cell proliferation and invasion through PI3K/AKT signaling pathway by targeting PTEN. Tumour
Biol. 2016;37(10): 13469 -77.
Jiang X, Zhang X. The molecular pathogenesis of pituitary adenomas: an update. Endocrinol
Metab. 2013;28(4): 245-54.