STAT3 inhibitor WP1066 attenuates miRNA-21 to suppress human oral squamous cell carcinoma growth in vitro and in vivo. 2014

Xuan Zhou, and Yu Ren, and Aiqin Liu, and Lei Han, and Kailiang Zhang, and Shasha Li, and Peng Li, and Ping Li, and Chunsheng Kang, and Xudong Wang, and Lun Zhang
Department of Otorhinolaryngology and Maxillofacial Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Tianjin 300060, P.R. China.

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.

UI MeSH Term Description Entries
D008819 Mice, Nude Mutant mice homozygous for the recessive gene "nude" which fail to develop a thymus. They are useful in tumor studies and studies on immune responses. Athymic Mice,Mice, Athymic,Nude Mice,Mouse, Athymic,Mouse, Nude,Athymic Mouse,Nude Mouse
D009062 Mouth Neoplasms Tumors or cancer of the MOUTH. Cancer of Mouth,Mouth Cancer,Oral Cancer,Oral Neoplasms,Cancer of the Mouth,Neoplasms, Mouth,Neoplasms, Oral,Cancer, Mouth,Cancer, Oral,Cancers, Mouth,Cancers, Oral,Mouth Cancers,Mouth Neoplasm,Neoplasm, Mouth,Neoplasm, Oral,Oral Cancers,Oral Neoplasm
D011725 Pyridines Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.
D002294 Carcinoma, Squamous Cell A carcinoma derived from stratified SQUAMOUS EPITHELIAL CELLS. It may also occur in sites where glandular or columnar epithelium is normally present. (From Stedman, 25th ed) Carcinoma, Epidermoid,Carcinoma, Planocellular,Carcinoma, Squamous,Squamous Cell Carcinoma,Carcinomas, Epidermoid,Carcinomas, Planocellular,Carcinomas, Squamous,Carcinomas, Squamous Cell,Epidermoid Carcinoma,Epidermoid Carcinomas,Planocellular Carcinoma,Planocellular Carcinomas,Squamous Carcinoma,Squamous Carcinomas,Squamous Cell Carcinomas
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015850 Interleukin-6 A cytokine that stimulates the growth and differentiation of B-LYMPHOCYTES and is also a growth factor for HYBRIDOMAS and plasmacytomas. It is produced by many different cells including T-LYMPHOCYTES; MONOCYTES; and FIBROBLASTS. Hepatocyte-Stimulating Factor,Hybridoma Growth Factor,IL-6,MGI-2,Myeloid Differentiation-Inducing Protein,Plasmacytoma Growth Factor,B Cell Stimulatory Factor-2,B-Cell Differentiation Factor,B-Cell Differentiation Factor-2,B-Cell Stimulatory Factor 2,B-Cell Stimulatory Factor-2,BSF-2,Differentiation Factor, B-Cell,Differentiation Factor-2, B-Cell,IFN-beta 2,IL6,Interferon beta-2,B Cell Differentiation Factor,B Cell Differentiation Factor 2,B Cell Stimulatory Factor 2,Differentiation Factor 2, B Cell,Differentiation Factor, B Cell,Differentiation-Inducing Protein, Myeloid,Growth Factor, Hybridoma,Growth Factor, Plasmacytoma,Hepatocyte Stimulating Factor,Interferon beta 2,Interleukin 6,Myeloid Differentiation Inducing Protein,beta-2, Interferon
D016601 RNA-Binding Proteins Proteins that bind to RNA molecules. Included here are RIBONUCLEOPROTEINS and other proteins whose function is to bind specifically to RNA. Double-Stranded RNA-Binding Protein,Double-Stranded RNA-Binding Proteins,ds RNA-Binding Protein,RNA-Binding Protein,ds RNA-Binding Proteins,Double Stranded RNA Binding Protein,Double Stranded RNA Binding Proteins,Protein, Double-Stranded RNA-Binding,Protein, ds RNA-Binding,RNA Binding Protein,RNA Binding Proteins,RNA-Binding Protein, Double-Stranded,RNA-Binding Protein, ds,RNA-Binding Proteins, Double-Stranded,ds RNA Binding Protein
D017209 Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, i.e., DNA FRAGMENTATION. It is genetically programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Apoptosis, Extrinsic Pathway,Apoptosis, Intrinsic Pathway,Caspase-Dependent Apoptosis,Classic Apoptosis,Classical Apoptosis,Programmed Cell Death,Programmed Cell Death, Type I,Apoptoses, Extrinsic Pathway,Apoptoses, Intrinsic Pathway,Apoptosis, Caspase-Dependent,Apoptosis, Classic,Apoptosis, Classical,Caspase Dependent Apoptosis,Cell Death, Programmed,Classic Apoptoses,Extrinsic Pathway Apoptoses,Extrinsic Pathway Apoptosis,Intrinsic Pathway Apoptoses,Intrinsic Pathway Apoptosis
D045744 Cell Line, Tumor A cell line derived from cultured tumor cells. Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines

Related Publications

Xuan Zhou, and Yu Ren, and Aiqin Liu, and Lei Han, and Kailiang Zhang, and Shasha Li, and Peng Li, and Ping Li, and Chunsheng Kang, and Xudong Wang, and Lun Zhang
May 2014, Zhonghua kou qiang yi xue za zhi = Zhonghua kouqiang yixue zazhi = Chinese journal of stomatology,
Xuan Zhou, and Yu Ren, and Aiqin Liu, and Lei Han, and Kailiang Zhang, and Shasha Li, and Peng Li, and Ping Li, and Chunsheng Kang, and Xudong Wang, and Lun Zhang
May 2010, British journal of cancer,
Xuan Zhou, and Yu Ren, and Aiqin Liu, and Lei Han, and Kailiang Zhang, and Shasha Li, and Peng Li, and Ping Li, and Chunsheng Kang, and Xudong Wang, and Lun Zhang
August 2022, International journal of molecular sciences,
Xuan Zhou, and Yu Ren, and Aiqin Liu, and Lei Han, and Kailiang Zhang, and Shasha Li, and Peng Li, and Ping Li, and Chunsheng Kang, and Xudong Wang, and Lun Zhang
August 2016, International journal of molecular sciences,
Xuan Zhou, and Yu Ren, and Aiqin Liu, and Lei Han, and Kailiang Zhang, and Shasha Li, and Peng Li, and Ping Li, and Chunsheng Kang, and Xudong Wang, and Lun Zhang
November 2018, Oncology letters,
Xuan Zhou, and Yu Ren, and Aiqin Liu, and Lei Han, and Kailiang Zhang, and Shasha Li, and Peng Li, and Ping Li, and Chunsheng Kang, and Xudong Wang, and Lun Zhang
June 2021, Oncogene,
Xuan Zhou, and Yu Ren, and Aiqin Liu, and Lei Han, and Kailiang Zhang, and Shasha Li, and Peng Li, and Ping Li, and Chunsheng Kang, and Xudong Wang, and Lun Zhang
December 2023, Head and neck pathology,
Xuan Zhou, and Yu Ren, and Aiqin Liu, and Lei Han, and Kailiang Zhang, and Shasha Li, and Peng Li, and Ping Li, and Chunsheng Kang, and Xudong Wang, and Lun Zhang
January 2020, International journal of nanomedicine,
Xuan Zhou, and Yu Ren, and Aiqin Liu, and Lei Han, and Kailiang Zhang, and Shasha Li, and Peng Li, and Ping Li, and Chunsheng Kang, and Xudong Wang, and Lun Zhang
December 2023, Cell biochemistry and function,
Xuan Zhou, and Yu Ren, and Aiqin Liu, and Lei Han, and Kailiang Zhang, and Shasha Li, and Peng Li, and Ping Li, and Chunsheng Kang, and Xudong Wang, and Lun Zhang
May 2020, Cell death & disease,
Copied contents to your clipboard!