Abstract |
Abnormalities in signal transducer and activator of transcription 3 (STAT3) are involved in the oncogenesis of oral squamous cell carcinoma (OSCC). MicroRNA-21 (miR-21) is an important gene expression regulator to OSCC. miR-21 induction by STAT3 has been reported in multiple human cancers. In the present study, we found that STAT3 (-/p) expression was positively correlated with miR-21 in 60 OSCC samples. A reporter gene assay showed that miR-21 overexpression was dependent on STAT3 activation. WP1066, a small molecular inhibitor of STAT3, was used to suppress STAT3 expression in OSCC cells. TSCCA and TCA8113 showed reduction in tumor cell proliferation, invasion ability and miR-21 expression by WP1066 treatment. In addition, the expression of miR-21 target proteins [programmed cell death 4 (PDCD4), tissue inhibitor of metalloproteinase 3 (TIMP-3) and phosphatase and tensin homolog (PTEN)] was upregulated. Restored STAT3 expression by IL-6 induced miR-21 overexpression, which further confirmed the correlation between STAT3 and miR-21. WP1066 inhibited tumor growth and induced tumor cell apoptosis in the TSCCA xenograft tumor model. Western blotting and immunohistochemistry staining indicated that STAT3 (-/p), Ki67, Bcl-2 and MMP-2 expressions decreased in the WP1066-treated group; PDCD4, TIMP-3 and PTEN expression increased simulta-neously. The present study provides evidence that targeting STAT3 could regulate OSCC cell growth in a miR-21-dependent manner and WP1066 could be a novel candidate drug to treat OSCC by inhibiting STAT3/miR-21 axis.
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Authors | Xuan Zhou, Yu Ren, Aiqin Liu, Lei Han, Kailiang Zhang, Shasha Li, Peng Li, Ping Li, Chunsheng Kang, Xudong Wang, Lun Zhang |
Journal | Oncology reports
(Oncol Rep)
Vol. 31
Issue 5
Pg. 2173-80
(May 2014)
ISSN: 1791-2431 [Electronic] Greece |
PMID | 24676554
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Apoptosis Regulatory Proteins
- IL6 protein, human
- Interleukin-6
- Ki-67 Antigen
- MIRN21 microRNA, human
- MicroRNAs
- PDCD4 protein, human
- Proto-Oncogene Proteins c-bcl-2
- Pyridines
- RNA-Binding Proteins
- STAT3 Transcription Factor
- STAT3 protein, human
- TIMP3 protein, human
- Tissue Inhibitor of Metalloproteinase-3
- Tyrphostins
- WP1066
- PTEN Phosphohydrolase
- PTEN protein, human
- Matrix Metalloproteinase 2
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Topics |
- Animals
- Apoptosis
(drug effects)
- Apoptosis Regulatory Proteins
(biosynthesis)
- Carcinoma, Squamous Cell
(drug therapy)
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Humans
- Interleukin-6
(metabolism)
- Ki-67 Antigen
(biosynthesis)
- Matrix Metalloproteinase 2
(biosynthesis)
- Mice
- Mice, Nude
- MicroRNAs
(antagonists & inhibitors, biosynthesis)
- Mouth Neoplasms
(drug therapy)
- PTEN Phosphohydrolase
(biosynthesis)
- Proto-Oncogene Proteins c-bcl-2
(biosynthesis)
- Pyridines
(pharmacology)
- RNA-Binding Proteins
(biosynthesis)
- STAT3 Transcription Factor
(antagonists & inhibitors, biosynthesis)
- Tissue Inhibitor of Metalloproteinase-3
(biosynthesis)
- Tyrphostins
(pharmacology)
- Xenograft Model Antitumor Assays
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