PMID- 29938004
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240327
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 9
IP  - 44
DP  - 2018 Jun 8
TI  - High miR-100 expression is associated with aggressive features and modulates 
      TORC1 complex activation in lung carcinoids.
PG  - 27535-27546
LID - 10.18632/oncotarget.25541 [doi]
AB  - PURPOSE: Mammalian target of rapamycin (mTOR) is a promising therapeutic target 
      in advanced lung carcinoid patients. However, the mechanisms of mTOR modulation 
      and of responsiveness to mTOR inhibitors are largely unclear. Our aim was to 
      analyze the expression and functional role of specific miRNAs in lung carcinoids 
      as an alternative mechanism targeting mTOR pathway. EXPERIMENTAL DESIGN: Seven 
      miRNAs, selected by bioinformatic tools and literature search, were analyzed in 
      142 lung neuroendocrine neoplasms (92 carcinoids and a control group of 50 high 
      grade neuroendocrine carcinomas), and compared with mTOR mRNA expression and 
      clinical/pathological parameters. Tissue results were validated in vitro in two 
      lung carcinoid cell lines by specific RNA interference and 
      biological/pharmacological tests. RESULTS: Tissutal expression of five miRNAs 
      (miR-99b, miR-100, miR-155, miR-193a-3p, miR-193a-5p) was inversely correlated 
      with mTOR mRNA expression, supporting their role in the negative regulation of 
      mTOR transcription. High expression of miR-100, miR-193a-3p and miR-193a-5p was 
      associated with aggressive features and, for the former two, with shorter time to 
      progression. In H727 and UMC11 lung carcinoid cells, miR-100 modulated mTOR RNA 
      and TORC1 complex protein expression, positively promoted cell migration and 
      negatively influenced cell proliferation. Moreover, miR-100 directly influenced 
      responsiveness of H727 and UMC11 cells to rapamycin. CONCLUSIONS: MiR-100 
      actively participates to the regulation of mTOR expression in lung carcinoids and 
      represents a novel candidate prognostic biomarker for this tumor type; moreover, 
      inhibition of its expression is associated to increased responsiveness to mTOR 
      inhibitors and might represent a novel strategy to sensitize lung carcinoids to 
      these target agents.
FAU - Rapa, Ida
AU  - Rapa I
AD  - Department of Oncology at San Luigi Hospital, University of Turin, Turin, Italy.
FAU - Votta, Arianna
AU  - Votta A
AD  - Department of Oncology at San Luigi Hospital, University of Turin, Turin, Italy.
FAU - Gatti, Gaia
AU  - Gatti G
AD  - Department of Oncology at San Luigi Hospital, University of Turin, Turin, Italy.
FAU - Izzo, Stefania
AU  - Izzo S
AD  - Department of Oncology at San Luigi Hospital, University of Turin, Turin, Italy.
FAU - Buono, Nicola Lo
AU  - Buono NL
AD  - Department of Medical Sciences, University of Turin, Turin, Italy.
FAU - Giorgio, Elisa
AU  - Giorgio E
AD  - Department of Medical Sciences, University of Turin, Turin, Italy.
FAU - Vatrano, Simona
AU  - Vatrano S
AD  - Department of Oncology at San Luigi Hospital, University of Turin, Turin, Italy.
FAU - Napoli, Francesca
AU  - Napoli F
AD  - Department of Oncology at San Luigi Hospital, University of Turin, Turin, Italy.
FAU - Scarpa, Aldo
AU  - Scarpa A
AD  - ARC-NET Applied Research on Cancer Centre at Department of Diagnostics and Public 
      Health, Section of Pathology, University and Hospital Trust of Verona, Verona, 
      Italy.
FAU - Scagliotti, Giorgio
AU  - Scagliotti G
AD  - Department of Oncology at San Luigi Hospital, University of Turin, Turin, Italy.
FAU - Papotti, Mauro
AU  - Papotti M
AD  - Department of Oncology at San Luigi Hospital, University of Turin, Turin, Italy.
FAU - Volante, Marco
AU  - Volante M
AD  - Department of Oncology at San Luigi Hospital, University of Turin, Turin, Italy.
LA  - eng
PT  - Journal Article
DEP - 20180608
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
PMC - PMC6007959
OTO - NOTNLM
OT  - lung carcinoids
OT  - mTOR
OT  - miR-100
OT  - miRNAs
OT  - rapamycin sensitivity
COIS- CONFLICTS OF INTEREST All Authors declare the absence of any conflict of 
      interest.
EDAT- 2018/06/26 06:00
MHDA- 2018/06/26 06:01
PMCR- 2018/06/08
CRDT- 2018/06/26 06:00
PHST- 2017/11/09 00:00 [received]
PHST- 2018/05/14 00:00 [accepted]
PHST- 2018/06/26 06:00 [entrez]
PHST- 2018/06/26 06:00 [pubmed]
PHST- 2018/06/26 06:01 [medline]
PHST- 2018/06/08 00:00 [pmc-release]
AID - 25541 [pii]
AID - 10.18632/oncotarget.25541 [doi]
PST - epublish
SO  - Oncotarget. 2018 Jun 8;9(44):27535-27546. doi: 10.18632/oncotarget.25541. 
      eCollection 2018 Jun 8.