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Targeting the SMO oncogene by miR-326 inhibits glioma biological behaviors and stemness.
Du, Wenzhong; Liu, Xing; Chen, Lingchao; Dou, Zhijin; Lei, Xuhui; Chang, Liang; Cai, Jinquan; Cui, Yuqiong; Yang, Dongbo; Sun, Ying; Li, Yongli; Jiang, Chuanlu.
Afiliação
  • Du W; Department of Neurosurgery, Second Affiliated Hospital of Harbin Medical University, Harbin, China (W.D., X.L., Z.D., X.L., L.C., J.C., Y.C., D.Y., Y.S., Y.L., C.J.); Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China (L.C.).
  • Liu X; Department of Neurosurgery, Second Affiliated Hospital of Harbin Medical University, Harbin, China (W.D., X.L., Z.D., X.L., L.C., J.C., Y.C., D.Y., Y.S., Y.L., C.J.); Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China (L.C.).
  • Chen L; Department of Neurosurgery, Second Affiliated Hospital of Harbin Medical University, Harbin, China (W.D., X.L., Z.D., X.L., L.C., J.C., Y.C., D.Y., Y.S., Y.L., C.J.); Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China (L.C.).
  • Dou Z; Department of Neurosurgery, Second Affiliated Hospital of Harbin Medical University, Harbin, China (W.D., X.L., Z.D., X.L., L.C., J.C., Y.C., D.Y., Y.S., Y.L., C.J.); Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China (L.C.).
  • Lei X; Department of Neurosurgery, Second Affiliated Hospital of Harbin Medical University, Harbin, China (W.D., X.L., Z.D., X.L., L.C., J.C., Y.C., D.Y., Y.S., Y.L., C.J.); Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China (L.C.).
  • Chang L; Department of Neurosurgery, Second Affiliated Hospital of Harbin Medical University, Harbin, China (W.D., X.L., Z.D., X.L., L.C., J.C., Y.C., D.Y., Y.S., Y.L., C.J.); Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China (L.C.).
  • Cai J; Department of Neurosurgery, Second Affiliated Hospital of Harbin Medical University, Harbin, China (W.D., X.L., Z.D., X.L., L.C., J.C., Y.C., D.Y., Y.S., Y.L., C.J.); Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China (L.C.).
  • Cui Y; Department of Neurosurgery, Second Affiliated Hospital of Harbin Medical University, Harbin, China (W.D., X.L., Z.D., X.L., L.C., J.C., Y.C., D.Y., Y.S., Y.L., C.J.); Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China (L.C.).
  • Yang D; Department of Neurosurgery, Second Affiliated Hospital of Harbin Medical University, Harbin, China (W.D., X.L., Z.D., X.L., L.C., J.C., Y.C., D.Y., Y.S., Y.L., C.J.); Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China (L.C.).
  • Sun Y; Department of Neurosurgery, Second Affiliated Hospital of Harbin Medical University, Harbin, China (W.D., X.L., Z.D., X.L., L.C., J.C., Y.C., D.Y., Y.S., Y.L., C.J.); Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China (L.C.).
  • Li Y; Department of Neurosurgery, Second Affiliated Hospital of Harbin Medical University, Harbin, China (W.D., X.L., Z.D., X.L., L.C., J.C., Y.C., D.Y., Y.S., Y.L., C.J.); Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China (L.C.).
  • Jiang C; Department of Neurosurgery, Second Affiliated Hospital of Harbin Medical University, Harbin, China (W.D., X.L., Z.D., X.L., L.C., J.C., Y.C., D.Y., Y.S., Y.L., C.J.); Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China (L.C.).
Neuro Oncol ; 17(2): 243-53, 2015 Feb.
Article em En | MEDLINE | ID: mdl-25173582
ABSTRACT

BACKGROUND:

Few studies have associated microRNAs (miRNAs) with the hedgehog (Hh) pathway. Here, we investigated whether targeting smoothened (SMO) with miR-326 would affect glioma biological behavior and stemness.

METHODS:

To investigate the expression of SMO and miR-326 in glioma specimens and cell lines, we utilized quantitative real-time (qRT)-PCR, Western blot, immunohistochemistry, and fluorescence in situ hybridization. The luciferase reporter assay was used to verify the relationship between SMO and miR-326. We performed cell counting kit-8, transwell, and flow cytometric assays using annexin-V labeling to detect changes after transfection with siRNA against SMO or miR-326. qRT-PCR assays, neurosphere formation, and immunofluorescence were utilized to detect the modification of self-renewal and stemness in U251 tumor stem cells. A U251-implanted intracranial model was used to study the effect of miR-326 on tumor volume and SMO suppression efficacy.

RESULTS:

SMO was upregulated in gliomas and was associated with tumor grade and survival period. SMO inhibition suppressed the biological behaviors of glioma cells. SMO expression was inversely correlated with miR-326 and was identified as a novel direct target of miR-326. miR-326 overexpression not only repressed SMO and downstream genes but also decreased the activity of the Hh pathway. Moreover, miR-326 overexpression decreased self-renewal and stemness and partially prompted differentiation in U251 tumor stem cells. In turn, the inhibition of Hh partially elevated miR-326 expression. Intracranial tumorigenicity induced by the transfection of miR-326 was reduced and was partially mediated by the decreased SMO expression.

CONCLUSIONS:

This work suggests a possible molecular mechanism of the miR- 326/SMO axis, which can be a potential alternative therapeutic pathway for gliomas.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Células-Tronco Neoplásicas / Neoplasias Encefálicas / Glioblastoma / MicroRNAs / Receptores Acoplados a Proteínas G Idioma: En Ano de publicação: 2015 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Células-Tronco Neoplásicas / Neoplasias Encefálicas / Glioblastoma / MicroRNAs / Receptores Acoplados a Proteínas G Idioma: En Ano de publicação: 2015 Tipo de documento: Article