PMID- 27233793
OWN - NLM
STAT- MEDLINE
DCOM- 20170920
LR  - 20211026
IS  - 1573-6822 (Electronic)
IS  - 0742-2091 (Linking)
VI  - 32
IP  - 4
DP  - 2016 Aug
TI  - Identification of a microRNA (miR-663a) induced by ER stress and its target gene 
      PLOD3 by a combined microRNome and proteome approach.
PG  - 285-303
LID - 10.1007/s10565-016-9335-z [doi]
AB  - INTRODUCTION: MicroRNAs (miRs) regulate gene expression to support important 
      physiological functions. Significant evidences suggest that miRs play a crucial 
      role in many pathological events and in the cell response to various stresses. 
      METHODS: With the aim to identify new miRs induced by perturbation of 
      intracellular calcium homeostasis, we analysed miR expression profiles of 
      thapsigargin (TG)-treated cells by microarray. In order to identify 
      miR-663a-regulated genes, we evaluated proteomic changes in 
      miR-663a-overexpressing cells by two-dimensional differential in-gel 
      electrophoresis coupled to mass spectrometric identification of the 
      differentially represented proteins. Microarray and proteomic analyses were 
      supported by biochemical validation. RESULTS: Results of microarray revealed 24 
      differentially expressed miRs; among them, miR-663a turned out to be by ER stress 
      and under the control of the PERK pathway of the unfolded protein response. 
      Proteomic analysis revealed that PLOD3, which is the gene encoding for 
      collagen-modifying lysyl hydroxylase 3 (LH3), is regulated by miR-663a. 
      Luciferase reporter assays demonstrated that miR-663a indeed reduces LH3 
      expression by targeting to 3'-UTR of PLOD3 mRNA. Interestingly, miR-663a 
      inhibition of LH3 expression generates reduced extracellular accumulation of type 
      IV collagen, thus suggesting the involvement of miR-663a in modulating collagen 4 
      secretion in physiological conditions and in response to ER stress. CONCLUSION: 
      The finding of the ER stress-induced PERK-miR-663a pathway may have important 
      implications in the understanding of the molecular mechanisms underlying the 
      function of this miR in normal and/or pathological conditions.
FAU - Amodio, Giuseppina
AU  - Amodio G
AD  - Dipartimento di Scienze Farmaceutiche, Universita degli Studi di Salerno, 84034, 
      Fisciano, Salerno, Italy.
FAU - Sasso, Emanuele
AU  - Sasso E
AD  - Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Universita degli 
      Studi di Napoli Federico II, 80131, Naples, Italy.
AD  - CEINGE Biotecnologie Avanzate, 80145, Naples, Italy.
FAU - D'Ambrosio, Chiara
AU  - D'Ambrosio C
AD  - Proteomics and Mass Spectrometry Laboratory, ISPAAM, National Research Council, 
      80147, Naples, Italy.
FAU - Scaloni, Andrea
AU  - Scaloni A
AD  - Proteomics and Mass Spectrometry Laboratory, ISPAAM, National Research Council, 
      80147, Naples, Italy.
FAU - Moltedo, Ornella
AU  - Moltedo O
AD  - Dipartimento di Scienze Farmaceutiche, Universita degli Studi di Salerno, 84034, 
      Fisciano, Salerno, Italy.
FAU - Franceschelli, Silvia
AU  - Franceschelli S
AD  - Dipartimento di Scienze Farmaceutiche, Universita degli Studi di Salerno, 84034, 
      Fisciano, Salerno, Italy.
FAU - Zambrano, Nicola
AU  - Zambrano N
AD  - Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Universita degli 
      Studi di Napoli Federico II, 80131, Naples, Italy.
AD  - CEINGE Biotecnologie Avanzate, 80145, Naples, Italy.
FAU - Remondelli, Paolo
AU  - Remondelli P
AD  - Dipartimento di Medicina, Chirurgia e Odontoiatria "Scuola Medica Salernitana", 
      Universita degli Studi di Salerno, 84034, Baronissi, Salerno, Italy. 
      premondelli@unisa.it.
AD  - Dipartimento di Medicina e Chirurgia, Universita degli Studi di Salerno, Via 
      Salvador Allende, I-84034, Baronissi, Salerno, Italy. premondelli@unisa.it.
LA  - eng
PT  - Journal Article
DEP - 20160527
PL  - Switzerland
TA  - Cell Biol Toxicol
JT  - Cell biology and toxicology
JID - 8506639
RN  - 0 (MIRN663 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (Proteome)
RN  - EC 1.14.11.- (PLOD3 protein, human)
RN  - EC 1.14.11.4 (Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase)
RN  - EC 2.7.11.1 (EIF2AK3 protein, human)
RN  - EC 2.7.11.1 (eIF-2 Kinase)
SB  - IM
MH  - Carcinoma, Hepatocellular/enzymology/genetics
MH  - Cell Line, Tumor
MH  - Endoplasmic Reticulum/enzymology/*genetics
MH  - Gene Expression Regulation
MH  - HEK293 Cells
MH  - HeLa Cells
MH  - Humans
MH  - Liver Neoplasms/enzymology/genetics
MH  - MicroRNAs/biosynthesis/*genetics/*metabolism
MH  - Oligonucleotide Array Sequence Analysis
MH  - Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase/*genetics/metabolism
MH  - Proteome/genetics/metabolism
MH  - Stress, Physiological/genetics
MH  - Transcriptome
MH  - eIF-2 Kinase/genetics/metabolism
OTO - NOTNLM
OT  - ER stress
OT  - Lysyl hydroxylase 3 (LH3)
OT  - MicroRNA
OT  - Mir 663a
OT  - PLOD3
OT  - Proteomics
EDAT- 2016/05/29 06:00
MHDA- 2017/09/21 06:00
CRDT- 2016/05/29 06:00
PHST- 2015/12/30 00:00 [received]
PHST- 2016/05/04 00:00 [accepted]
PHST- 2016/05/29 06:00 [entrez]
PHST- 2016/05/29 06:00 [pubmed]
PHST- 2017/09/21 06:00 [medline]
AID - 10.1007/s10565-016-9335-z [pii]
AID - 10.1007/s10565-016-9335-z [doi]
PST - ppublish
SO  - Cell Biol Toxicol. 2016 Aug;32(4):285-303. doi: 10.1007/s10565-016-9335-z. Epub 
      2016 May 27.