Knockdown of B3GNT3 inhibits colon cancer cell growth and migration

Colon cancer (CC) ranks among the most common malignant tumors globally. Providing theoretical support is essential to controlling CC and improving patients’ prognoses. Beta-1,3-N-acetylglucosaminyltransferase 3 (B3GNT3), a protein-coding gene that encodes a member of the B3GNT family, affects multiple tumors. However, B3GNT3 remains largely unknown in terms of its role and mechanism in CC development and metastasis. This study explored B3GNT3’s effect on CC progression. We revealed that B3GNT3 is highly expressed in human CC tissues. B3GNT3 depletion suppressed CC cell growth. Knocking down B3GNT3 restrained CC cells’ motility. Mechanically, B3GNT3 knockdown blocks the nuclear factor kappa-B (NF-κB) pathway in CC cells. In summary, B3GNT3 depletion restrained CC cells’ growth and motility by targeting NF-κB pathway. As a potential target for CC, B3GNT3 appears promising.

Colon cancer (CC); Beta-1,3-n-acetylglucosaminyltransferase 3 (B3GNT3); Growth; Motility; NF-κB pathway

[1] Garrett WS. The gut microbiota and colon cancer. Science. 2019; 364: 1133–1135.

[2] Khan FA, Albalawi R, Pottoo FH. Trends in targeted delivery of nanomaterials in colon cancer diagnosis and treatment. Medicinal Research Reviews. 2022; 42: 227–258.

[3] Markowitz SD, Dawson DM, Willis J, Willson JKV. Focus on colon cancer. Cancer Cell. 2002; 1: 233–236.

[4] Ma H, Chen X, Mo S, Zhang Y, Mao X, Chen J, et al. Targeting N-glycosylation of 4F2hc mediated by glycosyltransferase B3GNT3 sensitizes ferroptosis of pancreatic ductal adenocarcinoma. Cell Death & Differentiation. 2023; 30: 1988–2004.

[5] Zhuang H, Zhou Z, Zhang Z, Chen X, Ma Z, Huang S, et al. B3GNT3 overexpression promotes tumor progression and inhibits infiltration of CD8+ T cells in pancreatic cancer. Aging. 2021; 13: 2310–2329.

[6] Wang J, Ruan F, Guo L, Wang F, Wang F, An H. B3GNT3 acts as a carcinogenic factor in endometrial cancer via facilitating cell growth, invasion and migration through regulating RhoA/RAC1 pathway-associated markers. Genes & Genomics. 2021; 43: 447–457.

[7] Sun Y, Liu T, Xian L, Liu W, Liu J, Zhou H. B3GNT3, a direct target of miR-149-5p, promotes lung cancer development and indicates poor prognosis of lung cancer. Cancer Management and Research. 2020; 12: 2381–2391.

[8] Xu J, Guo Z, Yuan S, Li H, Luo S. Upregulation of B3GNT3 is associated with immune infiltration and activation of NF-kB pathway in gynecologic cancers. Journal of Reproductive Immunology. 2022; 152: 103658.

[9] Sun SC. Non-canonical NF-kB signaling pathway. Cell Research. 2011; 21: 71–85.

[10] Hayden MS, Ghosh S. Regulation of NF-kB by TNF family cytokines. Seminars in Immunology. 2014; 26: 253–266.

[11] Mirzaei S, Saghari S, Bassiri F, Raesi R, Zarrabi A, Hushmandi K, et al. NF-kB as a regulator of cancer metastasis and therapy response: a focus on epithelial-mesenchymal transition. Journal of Cellular Physiology. 2022; 237: 2770–2795.

[12] Yan R, Zhu H, Huang P, Yang M, Shen M, Pan Y, et al. Liquidambaric acid inhibits Wnt/b-catenin signaling and colon cancer via targeting TNF receptor-associated factor 2. Cell Reports. 2022; 38: 110319.

[13] Nakayama M, Oshima M. Mutant p53 in colon cancer. Journal of Molecular Cell Biology. 2019; 11: 267–276.

[14] Caval T, Alisson-Silva F, Schwarz F. Roles of glycosylation at the cancer cell surface: opportunities for large scale glycoproteomics. Theranostics. 2023; 13: 2605–2615.

[15] Li CW, Lim SO, Chung EM, Kim YS, Park AH, Yao J, et al. Eradication of triple-negative breast cancer cells by targeting glycosylated PD-L1. Cancer Cell. 2018; 33: 187–201.e10.

[16] Leng X, Wei S, Mei J, Deng S, Yang Z, Liu Z, et al. Identifying the prognostic significance of B3GNT3 with PD-L1 expression in lung adenocarcinoma. Translational Lung Cancer Research. 2021; 10: 965–980.

[17] Li Y, Wang X, Vural S, Mishra N, Cowan, K. B3GNT3 expression is a novel marker correlated with pelvic lymph node metastasis and poor clinical outcome in patients with early-stage cervical cancer. Cancer Management and Research. 2019; 11: 937–947.

[18] Zhang L, Zhou F, García de Vinuesa A, de Kruijf EM, Mesker WE, Hui L, et al. TRAF4 promotes TGF-β receptor signaling and drives breast cancer metastasis. Molecular Cell. 2020; 74: 1264–1275.e6.

[19] Liu M, Sakamaki T, Casimiro MC, Willmarth NE, Quong AA, Ju X, et al. The canonical NF-kB pathway governs mammary tumorigenesis in transgenic mice and tumor stem cell expansion. Cancer Research. 2010; 70: 10464–10473.

[20] Chen WP, Jin GJ, Xiong Y, Hu PF, Bao JP, Wu LD. Rosmarinic acid down-regulates NO and PGE2 expression via MAPK pathway in rat chondrocytes. Journal of Cellular and Molecular Medicine. 2018; 22: 346–353.