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. 2024 May 24;10(11):e31778.
doi: 10.1016/j.heliyon.2024.e31778. eCollection 2024 Jun 15.

C1GALT1 induces the carcinogenesis of thyroid cancer through regulation by miR-141-3p and GLUT1

Li Huang  1 , Zhen Li  1 , Ziguang Xu  1 , Ruili Yu  1 , Chao Ding  2 , Tingyi Sun  1 , Lingfei Kong  1 , Zhengchao Xia  3
Affiliations

C1GALT1 induces the carcinogenesis of thyroid cancer through regulation by miR-141-3p and GLUT1

Li Huang et al. Heliyon. .

Abstract

Core 1 β 1,3-galactosyltransferase 1 (C1GALT1) acts as an important glycosyltransferase in the occurrence and development of tumor glycosylation. However, the regulatory mechanisms of C1GALT1 in thyroid cancer (TC) is still unclear. In this study, we discovered that the expression level of C1GALT1 was significantly increased in thyroid adenocarcinoma tissues and cell lines (p < 0.01). Meanwhile, gene silencing of C1GALT1 inhibited the proliferation (CCK-8 assay), migration (wound healing), and invasion (Transwell) of TC cells (p < 0.05). Further investigation indicated that miR-141-3p had a negative correlation with C1GALT1 and suppressed cancer carcinogenesis in TC cells. Moreover, we first found that glucose transporter 1 (GLUT1) was a downstream element of C1GALT1 and was positively correlated with C1GALT1 levels in TC. The GLUT1 could reverse the inhibitory effects of siRNA C1GALT1 on cell development (p < 0.05). These data suggest that the miR-141-3p/C1GALT1/GLUT1 axis plays an essential role during TC progression and may be a probable biomarker or therapeutic target for thyroid cancer patients.

Keywords: C1GALT1; Carcinogenesis; GLUT1; Metastasis; Thyroid cancer; miR-141-3p.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
C1GALT1 is overexpressed in thyroid cancer tissues. (A) Heatmap of 56 lectins in the microarray analysis (n = 6). (B) The lectin expression levels of UEA-I, VVL and PNA. (C, D) C1GALT1 expression at the mRNA level (n = 30) and protein level (n = 6). (E) The enzyme activity of C1GALT1 in clinical specimens (n = 30). (F) The survival probability of different C1GALT1 expression levels in TC patients. The data are presented as the mean ± SD. ***p < 0.001.
Fig. 2
Fig. 2
C1GALT1 expression in TC cells. (A) The C1GALT1 levels of 16 TC cell lines in the CCLE database. (B, C) The mRNA (B) and protein (C) expression of C1GALT1 in the siRNA group compared to the blank group. (D) The PNA binding lectin blotting. Data are shown as the mean ± SD (n = 5, **p < 0.01).
Fig. 3
Fig. 3
C1GALT1 promotes carcinogenesis in TC cells. (A) Cell proliferation as determined by CCK-8. (B) Cell migration as determined by wound healing assay. (C) Cell invasion as determined by Transwell assay. (D) The protein expression of C1GALT1 after treatment with ITZ for 48 h. (E, F) The inhibitory effect of ITZ (8 μM) on cell migration (E) and invasion (F) levels. Data are expressed as the mean ± SD (n = 5, *p < 0.05, **p < 0.01, ***p < 0.001).
Fig. 4
Fig. 4
MiR-141-3p suppresses the function of C1GALT1. (A) Venn diagram of three publicly predicted miRNA databases. (B) The putative 3′UTR binding site between miR-141-3p and C1GALT1. (C) Dual-luciferase reporter assay. (D, E) The relative expression of C1GALT1 at the mRNA and protein levels. (F–H) Cell proliferation, migration and invasion assays. (I) Violin plot of relative miR-141-3p levels in TC tissues (n = 30). (J) The negative correlation of mRNA expression levels between miR-141-3p and C1GALT1 in clinical samples (n = 30). Data are presented as the mean ± SD (n = 5, *p < 0.05, **p < 0.01).
Fig. 5
Fig. 5
C1GALT1 positively regulates GLUT1 expression. (A) Heatmap of DMs in metabolomics (n = 3). (B) Violin plot of three typical DMs. (C) The KEGG enrichment pathway of DMs. (D) The higher expression of GLUT1 in TC cell lines according to the CCLE database. (E) The upper expression of GLUT1 in TC tissues by TCGA database. (F) GLUT1 protein levels in clinical specimens (n = 6). (G, H) The positive correlation of mRNA levels between GLUT1 and C1GALT1 in the Dependency Map database (G) and tissue samples (H, n = 30), respectively.
Fig. 6
Fig. 6
C1GALT1 increased migration and invasion by GLUT1. (A) The protein expression levels of GLUT1 after cotransfection with C1GALT1 siRNA and GLUT1 plasmid for 48 h. (B–D) Cell proliferation, migration and invasion assays. Data are presented as the mean ± SD (n = 5, *p < 0.05, **p < 0.01, SI: siRNA, G1: GLUT1).
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References

    1. Miller K.D., Nogueira L., Devasia T., et al. Cancer treatment and survivorship statistics, 2022. CA A Cancer J. Clin. 2022;72(5):409–436. doi: 10.3322/caac.21731. - DOI - PubMed
    1. Sung H., Ferlay J., Siegel R.L., et al. Global cancer statistics 2020: GLOBOCAN Estimates of incidence and Mortality worldwide for 36 cancers in 185 Countries. CA A Cancer J. Clin. 2021;71(3):209–249. doi: 10.3322/caac.21660. - DOI - PubMed
    1. Dupain C., Ali H.M., Mouhoub T.A., Urbinati G., Massaad-Massade L. Induction of TTF-1 or PAX-8 expression on proliferation and tumorigenicity in thyroid carcinomas. Int. J. Oncol. 2016 Sep;49(3):1248–1258. doi: 10.3892/ijo.2016.3617. - DOI - PubMed
    1. Chen D.W., Lang B.H.H., McLeod D.S.A., Newbold K., Haymart M.R. Thyroid cancer. Lancet. 2023;401(10387):1531–1544. doi: 10.1016/S0140-6736(23)00020-X. - DOI - PubMed
    1. Ali H.M., Maksimenko A., Urbinati G., et al. Effects of silencing the RET/PTC1 oncogene in papillary thyroid carcinoma by siRNA-squalene nanoparticles with and without fusogenic companion GALA-cholesterol. Thyroid. 2014 Feb;24(2):327–338. doi: 10.1089/thy.2012.0544. - DOI - PubMed

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