STAT3 inhibitor WP1066 attenuates miRNA-21 to suppress human oral squamous cell carcinoma growth in vitro and in vivo

Zhou,Xuan; Ren,Yu; Liu,Aiqin; Han,Lei; Zhang,Kailiang; Li,Shasha; Li,Peng; Li,Ping; Kang,Chunsheng; Wang,Xudong; Zhang,Lun

doi:10.3892/or.2014.3114

STAT3 inhibitor WP1066 attenuates miRNA-21 to suppress human oral squamous cell carcinoma growth in vitro and in vivo

Authors:
- Xuan Zhou
- Yu Ren
- Aiqin Liu
- Lei Han
- Kailiang Zhang
- Shasha Li
- Peng Li
- Ping Li
- Chunsheng Kang
- Xudong Wang
- Lun Zhang
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Affiliations: Department of Otorhinolaryngology and Maxillofacial Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Tianjin 300060, P.R. China, Tianjin Research Center of Basic Medical Science, Tianjin Medical University, Tianjin 300070, P.R. China, Tianjin Medical University General Hospital, Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin 300052, P.R. China, Tianjin Medical Information Institute, Tianjin 300070, P.R. China, Key Laboratory of Cancer Prevention and Therapy, Tianjin Cancer Institute, Tianjin 300060, P.R. China
Published online on: March 27, 2014 https://doi.org/10.3892/or.2014.3114
Pages: 2173-2180

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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 simultaneously. 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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