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

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

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)2173-2180
Number of pages8
JournalOncology reports
Volume31
Issue number5
DOIs
StatePublished - May 2014

Fingerprint

STAT3 Transcription Factor
MicroRNAs
Squamous Cell Carcinoma
Growth
Tissue Inhibitor of Metalloproteinase-3
Neoplasms
Phosphoric Monoester Hydrolases
WP1066
In Vitro Techniques
Apoptosis Regulatory Proteins
Matrix Metalloproteinases
Reporter Genes
Heterografts
Transcriptional Activation
Interleukin-6
Carcinogenesis
Cell Death
Western Blotting
Immunohistochemistry
Cell Proliferation

Keywords

  • Interleukin-6
  • MiRNA-21
  • Oral squamous cell carcinoma
  • Signal transducer and activator of transcription 3
  • WP1066

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

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.

In: Oncology reports, Vol. 31, No. 5, 05.2014, p. 2173-2180.

Research output: Contribution to journalArticle

Zhou, X, Ren, Y, Liu, A, Han, L, Zhang, K, Li, S, Li, P, Li, P, Kang, C, Wang, X & Zhang, L 2014, 'STAT3 inhibitor WP1066 attenuates miRNA-21 to suppress human oral squamous cell carcinoma growth in vitro and in vivo', Oncology reports, vol. 31, no. 5, pp. 2173-2180. https://doi.org/10.3892/or.2014.3114
Zhou, Xuan ; Ren, Yu ; Liu, Aiqin ; Han, Lei ; Zhang, Kailiang ; Li, Shasha ; Li, Peng ; Li, Ping ; Kang, Chunsheng ; Wang, Xudong ; Zhang, Lun. / STAT3 inhibitor WP1066 attenuates miRNA-21 to suppress human oral squamous cell carcinoma growth in vitro and in vivo. In: Oncology reports. 2014 ; Vol. 31, No. 5. pp. 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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AU - Zhou, Xuan

AU - Ren, Yu

AU - Liu, Aiqin

AU - Han, Lei

AU - Zhang, Kailiang

AU - Li, Shasha

AU - Li, Peng

AU - Li, Ping

AU - Kang, Chunsheng

AU - Wang, Xudong

AU - Zhang, Lun

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AB - 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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