PMID- 30389902
OWN - NLM
STAT- Publisher
LR  - 20240227
IS  - 1479-6805 (Electronic)
IS  - 0022-0795 (Print)
IS  - 0022-0795 (Linking)
VI  - 240
IP  - 1
DP  - 2018 Sep 1
TI  - MiR-15a/miR-16-1 expression inversely correlates with cyclin D1 levels in Men1 
      pituitary NETs.
PG  - 41-50
LID - JOE-18-0278.R2 [pii]
LID - 10.1530/JOE-18-0278 [doi]
AB  - Multiple Endocrine Neoplasia type 1 (MEN1) is an autosomal dominant disorder 
      characterised by the combined occurrence of parathyroid, pituitary and pancreatic 
      islet tumours, and is due to mutations of the MEN1 gene, which encodes the tumour 
      suppressor protein menin. Menin has multiple roles in genome stability, 
      transcription, cell division and proliferation, but its mechanistic roles in 
      tumourigenesis remain to be fully elucidated. MicroRNAs (miRNA) are non-coding 
      single stranded RNAs that post-transcriptionally regulate gene expression and 
      have been associated with tumour development, although the contribution of miRNAs 
      to MEN1-associated tumourigenesis and their relationship with menin expression 
      are not fully understood. Alterations in miRNA expression, including 
      downregulation of three putative 'tumour suppressor' miRNAs, miR-15a, miR-16-1 
      and let-7a, have been reported in several tumour types including non-MEN1 
      pituitary adenomas. We have therefore investigated the expression of miR-15a, 
      miR-16-1 and let-7a in pituitary tumours that developed after 12 months of age in 
      female mice with heterozygous knock out of the Men1 gene (Men1+/- mice). The 
      miRNAs miR-15a, miR-16-1 and let-7a were significantly downregulated in pituitary 
      tumours (by 2.3-fold, p<0.05; 2.1-fold p<0.01 and 1.6-fold p<0.05, respectively) 
      of Men1+/- mice, compared to normal wild type pituitaries. MiR-15a and miR-16-1 
      expression inversely correlated with expression of cyclin D1, a known 
      pro-tumourigenic target of these miRNAs, and knock down of menin in a human 
      cancer cell line (HeLa), and AtT20 mouse pituitary cell line resulted in 
      significantly decreased expression of miR-15a (p<0.05), indicating that the 
      decrease in miR-15a may be a direct result of lost menin expression.
FAU - Lines, Kate E
AU  - Lines KE
AD  - K Lines, University of Oxford, Radcliffe Department of Medicine, Oxford Centre 
      for Diabetes Endocrinology and Metabolism, Oxford, United Kingdom of Great 
      Britain and Northern Ireland.
FAU - Newey, Paul J
AU  - Newey PJ
AD  - P Newey, University of Oxford, Radcliffe Department of Medicine, Oxford Centre 
      for Diabetes Endocrinology and Metabolism, Oxford, United Kingdom of Great 
      Britain and Northern Ireland.
FAU - Yates, Christopher J
AU  - Yates CJ
AD  - C Yates, University of Oxford, Radcliffe Department of Medicine, Oxford Centre 
      for Diabetes Endocrinology and Metabolism, Oxford, United Kingdom of Great 
      Britain and Northern Ireland.
FAU - Stevenson, Mark
AU  - Stevenson M
AD  - M Stevenson, University of Oxford, Radcliffe Department of Medicine, Oxford 
      Centre for Diabetes Endocrinology and Metabolism, Oxford, United Kingdom of Great 
      Britain and Northern Ireland.
FAU - Dyar, Rebecca
AU  - Dyar R
AD  - R Dyar, University of Oxford, Radcliffe Department of Medicine, Oxford Centre for 
      Diabetes Endocrinology and Metabolism, Oxford, United Kingdom of Great Britain 
      and Northern Ireland.
FAU - Walls, Gerard V
AU  - Walls GV
AD  - G Walls, University of Oxford, Radcliffe Department of Medicine, Oxford Centre 
      for Diabetes Endocrinology and Metabolism, Oxford, United Kingdom of Great 
      Britain and Northern Ireland.
FAU - Bowl, Mike R
AU  - Bowl MR
AD  - M Bowl, University of Oxford, Radcliffe Department of Medicine, Oxford Centre for 
      Diabetes Endocrinology and Metabolism, Oxford, United Kingdom of Great Britain 
      and Northern Ireland.
FAU - Thakker, Rajesh V
AU  - Thakker RV
AD  - R Thakker, University of Oxford, Radcliffe Department of Medicine, Oxford Centre 
      for Diabetes Endocrinology and Metabolism, Oxford, United Kingdom of Great 
      Britain and Northern Ireland.
LA  - eng
GR  - G0501780/MRC_/Medical Research Council/United Kingdom
GR  - G0601423/MRC_/Medical Research Council/United Kingdom
GR  - G1000467/MRC_/Medical Research Council/United Kingdom
GR  - G9825289/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
DEP - 20180901
PL  - England
TA  - J Endocrinol
JT  - The Journal of endocrinology
JID - 0375363
PMC - PMC6347280
EDAT- 2018/11/06 06:00
MHDA- 2018/11/06 06:00
PMCR- 2019/01/25
CRDT- 2018/11/04 06:00
PHST- 2018/05/05 00:00 [received]
PHST- 2018/09/28 00:00 [accepted]
PHST- 2018/11/06 06:00 [pubmed]
PHST- 2018/11/06 06:00 [medline]
PHST- 2018/11/04 06:00 [entrez]
PHST- 2019/01/25 00:00 [pmc-release]
AID - JOE-18-0278.R2 [pii]
AID - JOE-18-0278 [pii]
AID - 10.1530/JOE-18-0278 [doi]
PST - aheadofprint
SO  - J Endocrinol. 2018 Sep 1;240(1):41-50. doi: 10.1530/JOE-18-0278.