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J Cell Biochem. 2019 Jun;120(6):10796-10811. doi: 10.1002/jcb.28371. Epub 2019 Jan 30.

SMAD3 inducing the transcription of  STYK1 to promote the EMT process and improve the tolerance of ovarian carcinoma cells to paclitaxel.

Author information

1
Department of Obstetrics and Gynecology, Peking University Frist Hospital, Beijing, China.

Abstract

OBJECTIVE:

To figure out the relationship between SMAD3 and serine-threonine tyrosine kinase (STYK1) in ovarian carcinoma cell's paclitaxel resistance.

METHODS:

The quantitative reverse transcription-polymerase chain reactpostion and Western blot analysis were used to analyze RNA and protein content of SMAD3 and STYK1, respectively. The chromatin immunoprecipitation assay was used to confirm the binding site of SMAD3 to the STYK1 promoter region. Transwell assay was used to detect cell invasion and migration, and Western Blot was used to detect the marker proteins (vimentin and E-cadherin) of epithelial-mesenchymal transition (EMT) process. MTT and apoptosis assay were used to, respectively, measure cell vitality and apoptosis. In vivo experiments, rats were subcutaneously implanted with A2780 cells to establish an animal model of ovarian cancer and the survival curve was drawn.

RESULTS:

Upregulating SMAD3 induced the expression of STYK1 in ovarian cancer cell lines. STYK1 is a direct transcriptional target of SMAD3. Upregulating STYK1 improved the paclitaxel resistance of ovarian carcinoma cells. Upregulating STYK1 promoted cell invasion, migration, and the EMT process, and SMAD3 had the same effect with STYK1 on cell invasion, cell migration, and the EMT process. The animal assay showed that downregulating STYK1 inhibited the EMT process and the paclitaxel resistance, further promoting the treatment of cervical cancer.

CONCLUSION:

SMAD3 combined with the promoter region of STYK1 to promote the transcription process of STYK1, thereby promoting the EMT process and paclitaxel resistance of ovarian cancer cells.

KEYWORDS:

EMT process; SMAD3; Serine threonine tyrosine kinase (STYK1); ovarian carcinoma; paclitaxel tolerance

PMID:
30701575
DOI:
10.1002/jcb.28371

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