Abstract
In this study, we aimed to explore the molecular role of Deltex E3 ubiquitin ligase 4 (DTX4) in thyroid cancer (TC) both in vitro and in vivo. The expression level of DTX4 in TC tissues was compared using The Cancer Genome Atlas (TCGA) database. We subsequently evaluated cell proliferation and migration in DTX4 knock down or DTX4 overexpression TC cell lines (TPC-1 and K1) by CCK-8, cell colony formation, and transwell assays. RNA sequencing and KEGG analysis were employed to identify potential genes that interact with DTX4. Our results showed that DTX4 was expressed at higher levels in both TC tissues and cells compared to normal controls. Knock down of DTX4 expression significantly inhibited TC cell progression in vitro. Furthermore, knockdown of endogenous DTX4 by shDTX4 markedly abrogated tumor growth, with significantly smaller tumor size and lower tumor weight in the shDTX4 group compared to the shCtrl group. Conversely, overexpression of DTX4 enhanced TC cell proliferation and migration. Through RNA sequencing, we identified 590 Differentially Expressed Genes (DEGs), with stearoyl-CoA desaturase 1 (SCD) ranking as the top gene. A positive correlation between DTX4 and SCD was observed in TC samples. Additionally, treatment with an SCD inhibitor, A939572, significantly rescued the enhanced growth effect induced by DTX4 overexpression. In conclusion, this study demonstrated that DTX4 promotes TC progression through SCD, indicating that the DTX4/SCD axis could be a promising target for TC therapy.
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The dataset used and/or analyzed in this study is available from the corresponding author on reasonable request.
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ZY designed the study. YC carried out the experiment and wrote the paper. JL and NB analyzed the data and discussed the result. YC and ZY revised the manuscript.
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The experimental procedure followed the United States National Institutes of Health Guide for the Care and Use of Laboratory Animals (NIH Publication No. 85–23, revised 1985). The study protocol was approved by the Animal Ethics Committee of Center for Integrative and Translational Medicine, Shandong Public Health Clinical Center (NO. ECAESDUSM 20123011).
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Cui, Y., Luo, J., Bai, N. et al. Deltex E3 ubiquitin ligase 4 promotes thyroid cancer progression through stearoyl-CoA desaturase 1. Funct Integr Genomics 23, 280 (2023). https://doi.org/10.1007/s10142-023-01215-9
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DOI: https://doi.org/10.1007/s10142-023-01215-9