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B3GNT3 acts as a carcinogenic factor in endometrial cancer via facilitating cell growth, invasion and migration through regulating RhoA/RAC1 pathway-associated markers

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Abstract

Background

Aberrant expression of beta-1,3-N-acetylglucosaminyltransferase-3 (B3GNT3) has been frequently clarified in various cancers, however, its role in endometrial cancer (EC) has not been assessed in detail.

Purpose

This study aimed to investigate the biological role of B3GNT3 in EC and simply explored the detailed mechanism.

Methods

The EC RNA-Seq dataset from TCGA database was applied to evaluate the expression of B3GNT3 and assess its role on prognostic value. HEC-1-A and KLE cell lines of EC were used to perform loss- and gain-of-function B3GNT3 assays respectively. Quantitative real-time PCR (qRT-PCR) and western blot were used to measure the mRNA and protein levels of indicated molecules respectively. Cell counting kit-8, clone formation tests, and Transwell assay served to determine the changes of proliferative, invasive and migratory abilities of EC cells after altering the expression of B3GNT3.

Results

B3GNT3 was found to be highly expressed in EC tissues compared to normal tissues according to the online public databases, which confirmed by the following qRT-PCR in 3 EC cell lines. Besides, high B3GNT3 expression presented a worse overall survival in EC patients as compared with low B3GNT3 expression group. Furthermore, functional experiments in vitro indicated that B3GNT3 could facilitate the cell growth, invasion and migration. Moreover, we found that downregulation of B3GNT3 significantly reduced the expression level of GTP-RhoA and GTP-RAC1, whereas upregulation of B3GNT3 presented the opposite results.

Conclusion

The results of current study demonstrate that B3GNT3 acts as an oncogene that promotes EC cells growth, invasion and migration possibly through regulating the RhoA/RAC1 signaling pathway-related markers, suggesting that B3GNT3 may be a candidate biomarker for EC therapeutic intervention.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Affiliated Hospital of **ing Medical University, **ing, 272029, Shandong, China

    Ji-Shui Wang & Fu-Ling Wang

  2. Department of Obstetrics, Affiliated Hospital of **ing Medical University, No.89 of Guhuai Road, **ing, 272029, Shandong, China

    Fang Ruan, Li-Zhu Guo, Feng-Ge Wang & Hong-Min An

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  1. Ji-Shui Wang
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  2. Fang Ruan
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  3. Li-Zhu Guo
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  4. Feng-Ge Wang
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  5. Fu-Ling Wang
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Correspondence to Hong-Min An.

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Wang, JS., Ruan, F., Guo, LZ. et al. B3GNT3 acts as a carcinogenic factor in endometrial cancer via facilitating cell growth, invasion and migration through regulating RhoA/RAC1 pathway-associated markers. Genes Genom 43, 447–457 (2021). https://doi.org/10.1007/s13258-021-01072-5

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