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miR-182-5p Induced by STAT3 Activation Promotes Glioma Tumorigenesis
- Source :
- Cancer Research. 76:4293-4304
- Publication Year :
- 2016
- Publisher :
- American Association for Cancer Research (AACR), 2016.
-
Abstract
- Malignant glioma is an often fatal type of cancer. Aberrant activation of STAT3 leads to glioma tumorigenesis. STAT3-induced transcription of protein-coding genes has been extensively studied; however, little is known about STAT3-regulated miRNA gene transcription in glioma tumorigenesis. In this study, we found that abnormal activation or decreased expression of STAT3 promotes or inhibits the expression of miR-182-5p, respectively. Bioinformatics analyses determined that tumor suppressor protocadherin-8 (PCDH8) is a candidate target gene of miR-182-5p. miR-182-5p negatively regulated PCDH8 expression by directly targeting its 3′-untranslated region. PCDH8 knockdown induced the proliferative and invasive capacities of glioma cells. Silencing of PCDH8 or miR-182-5p mimics could reverse the inhibitory effect of WP1066, a STAT3 inhibitor, or STAT3 knockdown in vitro and in vivo on glioma progression. Clinically, expression levels of PCDH8 were inversely correlated with those of p-STAT3 or miR-182-5p in glioblastoma tissues. These findings reveal that the STAT3/miR-182-5p/PCDH8 axis has a critical role in glioma tumorigenesis and that targeting the axis may provide a new therapeutic approach for human glioma. Cancer Res; 76(14); 4293–304. ©2016 AACR.
- Subjects :
- STAT3 Transcription Factor
0301 basic medicine
Cancer Research
medicine.disease_cause
Article
law.invention
Mice
03 medical and health sciences
0302 clinical medicine
Cell Movement
law
Cell Line, Tumor
Glioma
microRNA
medicine
Animals
Humans
Gene silencing
Neoplasm Invasiveness
STAT3
Cell Proliferation
Gene knockdown
biology
Brain Neoplasms
Computational Biology
Cadherins
medicine.disease
Protocadherins
MicroRNAs
030104 developmental biology
Oncology
030220 oncology & carcinogenesis
biology.protein
Cancer research
Suppressor
Carcinogenesis
Subjects
Details
- ISSN :
- 15387445 and 00085472
- Volume :
- 76
- Database :
- OpenAIRE
- Journal :
- Cancer Research
- Accession number :
- edsair.doi.dedup.....1a64c94e4b1780a76f458edd0d51b273