title: miR-182-5p Induced by STAT3 Activation Promotes Glioma Tumorigenesis.
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.
authors.affiliation: Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Jianfei
authors.initials: J
authors.lastname: Xue
authors.affiliation: Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Aidong
authors.initials: A
authors.lastname: Zhou
authors.affiliation: Department of Hematology, The First Affiliated Hospital, Chinese PLA General Hospital, Beijing, China.
authors.forename: Yamei
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Saint-Aaron
authors.initials: SA
authors.lastname: Morris
authors.affiliation: Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Kangyu
authors.initials: K
authors.lastname: Lin
authors.affiliation: Department of Genomic Medicine; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Samirkumar
authors.initials: S
authors.lastname: Amin
authors.affiliation: Department of Genomic Medicine; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Roeland
authors.initials: R
authors.lastname: Verhaak
authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Gregory
authors.initials: G
authors.lastname: Fuller
authors.affiliation: Department of Gastroenterology, Hepatology & Nutrition, The University of Texas MD Anderson Cancer Center, Houston, Texas. Program in Cancer Biology, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, Texas.
authors.forename: Keping
authors.initials: K
authors.lastname: Xie
authors.affiliation: Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Amy B
authors.initials: AB
authors.lastname: Heimberger
authors.affiliation: Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas. Program in Cancer Biology, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, Texas. suhuang@mdanderson.org.
authors.forename: Suyun
authors.initials: S
authors.lastname: Huang
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000209:etiology* / Q000473:pathology; D015820:Cadherins / Q000235:genetics / Q000502:physiology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D019295:Computational Biology; D005910:Glioma / Q000209:etiology* / Q000473:pathology; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000032:analysis / Q000502:physiology*; D009361:Neoplasm Invasiveness; D000091363:Protocadherins; D050796:STAT3 Transcription Factor / Q000502:physiology*
chemical_list: D015820:Cadherins; D035683:MicroRNAs; C538984:Mirn182 microRNA, human; C115816:PCDH8 protein, human; D000091363:Protocadherins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human