GINS2 promotes cell proliferation and inhibits cell apoptosis in thyroid cancer by regulating CITED2 and LOXL2

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Abstract

To explore the mechanisms of GINS2 on cell proliferation and apoptosis in thyroid cancer (TC) cells. Expressions of GINS2 were inhibited in K1 and SW579 cells using gene interference technology. The abilities of proliferation and apoptosis, and cell cycle were determined by MTT assay and flow cytometric assay. The downstream molecules of GINS2 were searched by microarray and bioinformatics and validated by qRT-PCR and western blotting. In the in vivo study, the tumor growth was compared and the whole-body fluorescent imaging was analyzed. After GINS2 was interfered, cell proliferation was significantly inhibited (P < 0.01) and apoptosis rate increased (P < 0.01) in both K1 and SW579 cells. Cell cycle changed significantly in K1 cells, but not in SW579 cells. With bioinformatics upstream analysis, TGF-β1 was found as the most significantly upstream regulator. Expressions of TGF-β1 and its downstream target molecules CITED2 and LOXL2 were validated and found downregulated significantly in mRNA and protein levels (P < 0.05). The results of the nude mouse xenograft assay suggested that the volume and weight of tumor in ones infected with shGINS2 were statistically smaller than controls (P < 0.05). GINS2 plays an important role in cell proliferation and apoptosis of thyroid cancer by regulating the expressions of CITED2 and LOXL2, which may be a potential biomarker for diagnosis or prognosis and a drug target for therapy.

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Acknowledgements

The study was supported by grants from National Natural Science Foundation of China (No. 81571718 and No. 81703791), Shanghai Municipal Commission of Health and Family Planning (No. 201740084), Key Specialty Construction Project of Pudong Health and Family Planning Commission of Shanghai (No. PWZzk2017-21), Science and Technology Development Fund (No. 14DZ1940605), Science and Technology Development Fund of Shanghai Pudong New Area (No. PKJ2017-Y13) and Talents Training Program of Seventh People’s Hospital of Shanghai University of TCM (No. XX2017-04).

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Correspondence to Wei Xia.

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