PMID- 28192397
OWN - NLM
STAT- MEDLINE
DCOM- 20170907
LR  - 20180511
IS  - 1476-5594 (Electronic)
IS  - 0950-9232 (Linking)
VI  - 36
IP  - 18
DP  - 2017 May 4
TI  - Downregulation of miR-218 contributes to epithelial-mesenchymal transition and
      tumor metastasis in lung cancer by targeting Slug/ZEB2 signaling.
PG  - 2577-2588
LID - 10.1038/onc.2016.414 [doi]
AB  - Epithelial-mesenchymal transition (EMT) has been recognized as a key element of
      cell migration and invasion in lung cancer; however, the underlying mechanisms
      are not fully elucidated. Recently, emerging evidence suggest that miRNAs have
      crucial roles in control of EMT and EMT-associated traits such as migration,
      invasion and chemoresistance. Here, we found that miR-218 expression levels were 
      significantly downregulated in lung cancer tissues compared with adjacent
      non-cancerous tissues, and the levels of miR-218 were significantly associated
      with histological grades and lymph node metastasis. Overexpression of miR-218
      inhibited cell migration and invasion as well as the EMT process. Of particular
      importance, miR-218 was involved in the metastatic process of lung cancer cells
      in vivo by suppressing local invasion and distant colonization. We identified
      Slug and ZEB2 as direct functional targets of miR-218. Inverse correlations were 
      observed between miR-218 levels and Slug/ZEB2 levels in cancer tissue samples. In
      addition, overexpression of miR-218 in H1299 increased chemosensitivity of cells 
      to cisplatin treatment through suppression of Slug and ZEB2. These findings
      highlight an important role of miR-218 in the regulation of EMT-related traits
      and metastasis of lung cancer in part by modulation of Slug/ZEB2 signaling, and
      provide a potential therapeutic strategy by targeting miR-218 in NSCLC.
FAU - Shi, Z-M
AU  - Shi ZM
AD  - Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical
      University, Nanjing, China.
AD  - State Key Lab of Reproductive Medicine, Key Laboratory of Human Functional
      Genomics of Jiangsu Province, Jiangsu Key Laboratory of Cancer Biomarkers,
      Prevention, and Treatment, Cancer Center, Department of Pathology, Nanjing
      Medical University, Nanjing, China.
FAU - Wang, L
AU  - Wang L
AD  - State Key Lab of Reproductive Medicine, Key Laboratory of Human Functional
      Genomics of Jiangsu Province, Jiangsu Key Laboratory of Cancer Biomarkers,
      Prevention, and Treatment, Cancer Center, Department of Pathology, Nanjing
      Medical University, Nanjing, China.
FAU - Shen, H
AU  - Shen H
AD  - Department of Oncology, The First Affiliated Hospital of Nanjing Medical
      University, Nanjing, China.
FAU - Jiang, C-F
AU  - Jiang CF
AD  - State Key Lab of Reproductive Medicine, Key Laboratory of Human Functional
      Genomics of Jiangsu Province, Jiangsu Key Laboratory of Cancer Biomarkers,
      Prevention, and Treatment, Cancer Center, Department of Pathology, Nanjing
      Medical University, Nanjing, China.
FAU - Ge, X
AU  - Ge X
AD  - State Key Lab of Reproductive Medicine, Key Laboratory of Human Functional
      Genomics of Jiangsu Province, Jiangsu Key Laboratory of Cancer Biomarkers,
      Prevention, and Treatment, Cancer Center, Department of Pathology, Nanjing
      Medical University, Nanjing, China.
FAU - Li, D-M
AU  - Li DM
AD  - State Key Lab of Reproductive Medicine, Key Laboratory of Human Functional
      Genomics of Jiangsu Province, Jiangsu Key Laboratory of Cancer Biomarkers,
      Prevention, and Treatment, Cancer Center, Department of Pathology, Nanjing
      Medical University, Nanjing, China.
FAU - Wen, Y-Y
AU  - Wen YY
AD  - State Key Lab of Reproductive Medicine, Key Laboratory of Human Functional
      Genomics of Jiangsu Province, Jiangsu Key Laboratory of Cancer Biomarkers,
      Prevention, and Treatment, Cancer Center, Department of Pathology, Nanjing
      Medical University, Nanjing, China.
FAU - Sun, H-R
AU  - Sun HR
AD  - State Key Lab of Reproductive Medicine, Key Laboratory of Human Functional
      Genomics of Jiangsu Province, Jiangsu Key Laboratory of Cancer Biomarkers,
      Prevention, and Treatment, Cancer Center, Department of Pathology, Nanjing
      Medical University, Nanjing, China.
FAU - Pan, M-H
AU  - Pan MH
AD  - Department of Pathology, The First Affiliated Hospital of Nanjing Medical
      University, Nanjing, China.
FAU - Li, W
AU  - Li W
AD  - Department of Pathology, Affiliated Drum Tower Hospital of Nanjing University
      Medical School, Nanjing, China.
FAU - Shu, Y-Q
AU  - Shu YQ
AD  - Department of Oncology, The First Affiliated Hospital of Nanjing Medical
      University, Nanjing, China.
FAU - Liu, L-Z
AU  - Liu LZ
AD  - Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University,
      Philadelphia, PA, USA.
FAU - Peiper, S C
AU  - Peiper SC
AD  - Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University,
      Philadelphia, PA, USA.
FAU - He, J
AU  - He J
AD  - Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University,
      Philadelphia, PA, USA.
FAU - Jiang, B-H
AU  - Jiang BH
AD  - State Key Lab of Reproductive Medicine, Key Laboratory of Human Functional
      Genomics of Jiangsu Province, Jiangsu Key Laboratory of Cancer Biomarkers,
      Prevention, and Treatment, Cancer Center, Department of Pathology, Nanjing
      Medical University, Nanjing, China.
AD  - Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University,
      Philadelphia, PA, USA.
LA  - eng
GR  - R01 CA193511/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20170213
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Homeodomain Proteins)
RN  - 0 (MIRN218 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (Repressor Proteins)
RN  - 0 (SNAI1 protein, human)
RN  - 0 (Snail Family Transcription Factors)
RN  - 0 (ZEB2 protein, human)
RN  - 0 (Zinc Finger E-box Binding Homeobox 2)
RN  - Q20Q21Q62J (Cisplatin)
SB  - IM
MH  - A549 Cells
MH  - Animals
MH  - Cell Movement/genetics
MH  - Cisplatin/administration & dosage
MH  - Drug Resistance, Neoplasm/genetics
MH  - Epithelial-Mesenchymal Transition/genetics
MH  - Gene Expression Regulation, Neoplastic
MH  - Homeodomain Proteins/*genetics
MH  - Humans
MH  - Lung Neoplasms/drug therapy/*genetics/pathology
MH  - Mice
MH  - MicroRNAs/*genetics
MH  - Neoplasm Invasiveness/genetics/pathology
MH  - Repressor Proteins/*genetics
MH  - Snail Family Transcription Factors/*genetics
MH  - Xenograft Model Antitumor Assays
MH  - Zinc Finger E-box Binding Homeobox 2
PMC - PMC5422710
EDAT- 2017/02/14 06:00
MHDA- 2017/09/08 06:00
CRDT- 2017/02/14 06:00
PHST- 2016/03/24 00:00 [received]
PHST- 2016/08/03 00:00 [revised]
PHST- 2016/09/02 00:00 [accepted]
PHST- 2017/02/14 06:00 [pubmed]
PHST- 2017/09/08 06:00 [medline]
PHST- 2017/02/14 06:00 [entrez]
AID - onc2016414 [pii]
AID - 10.1038/onc.2016.414 [doi]
PST - ppublish
SO  - Oncogene. 2017 May 4;36(18):2577-2588. doi: 10.1038/onc.2016.414. Epub 2017 Feb
      13.