GTSE1 promotes prostate cancer cell proliferation via the SP1/FOXM1 signaling pathway

Laboratory Investigation (2020)Cite this article

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Abstract

G2 and S phase-expressed-1 (GTSE1) has been implicated in the pathogenesis of several malignant tumors. However, its specific role in prostate cancer (PCa) remains unclear. In this study, RNA-Seq data from patients with PCa and controls were downloaded from the FIREBROWSE database, and it was found that the GTSE1 mRNA level was significantly upregulated in PCa. Moreover, patients with higher GTSE1 mRNA levels had higher Gleason scores (P < 0.001), a more advanced pT stage (P = 0.011), and a more advanced pN stage (P = 0.006) as well as a shorter time to biochemical recurrence (P = 0.005). In addition, overexpression of GTSE1 could promote proliferation in LNCaP cells, whereas silencing GTSE1 could inhibit the growth of C4-2 cells in vitro and in vivo. Mechanistically, GTSE1 enhanced the expression of FOXM1 by upregulating the SP1 protein level, a transcription factor of FOXM1, which ultimately promoted PCa cell proliferation. In summary, GTSE1 is a new candidate oncogene in the development and progression of PCa, and it can promote PCa cell proliferation via the SP1/FOXM1 signaling pathway.

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Fig. 1: GTSE1 expression was upregulated in prostate cancer.
Fig. 2: The mRNA level of GTSE1 correlates with biochemical recurrence in prostate cancer.
Fig. 3: GTSE1 promotes prostate cancer cell proliferation in vitro and in vivo.
Fig. 4: Gene co-expression and enrichment analyses.
Fig. 5: GTSE1 promotes prostate cancer proliferation via the SP1/FOXM1 signaling pathway.
Fig. 6: GTSE1 promotes the proliferation of prostate cancer cell via SP1/FOXM1 signaling pathway.

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Acknowledgements

This study was supported by grants from the Natural Science Foundation of China (81874095 and 82072820) and the Guangdong Basic and Applied Basic Research Project Major Program of China (2019B1515120007).

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Author notes

  1. These authors contributed equally: Wenjie Lai, Weian Zhu

Affiliations

  1. Department of Urology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China

    Wenjie Lai, Weian Zhu, Yu Wang, Mingzhao Li & Xingqiao Wen

  2. Department of Health Care, Shenzhen Hospital, Southern Medical University, Shenzhen, China

    Xiaojuan Li

  3. Department of Urology, Yue Bei People’s Hospital, Shaoguan, China

    Yuefu Han

  4. Department of Urology, The Affiliated Zhongshan Hospital, Sun Yat-Sen University, Zhongshan, China

    Qu Leng

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  1. Wenjie Lai
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Contributions

XW designed the study. WL and WZ conducted experiments and participated in writing the manuscript. XL and YH were responsible for the statistical analysis. YW, QL, and ML collected the clinical specimens and clinical data. All authors read and approved the final manuscript.

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Correspondence to Xingqiao Wen.

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The Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China ensured that all sample information was kept confidential.

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Lai, W., Zhu, W., Li, X. et al. GTSE1 promotes prostate cancer cell proliferation via the SP1/FOXM1 signaling pathway. Lab Invest (2020). https://doi.org/10.1038/s41374-020-00510-4

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