Choline-induced SLC5A7 impairs colorectal cancer growth by stabilizing p53 protein

Yin, Yuan; Jiang, Zhiyuan; Fu, Jiayi; Yang, Li; Fang, Chao; Yin, Xiaonan; Chen, Ye; Chen, Na; Li, Junshu; Ji, Yanhong; Su, Xiaolan; Meng, Qingcai; Huang, Wei; Zhang, Bo; Deng, Hongxin; Dai, Lei

doi:10.1016/j.canlet.2021.09.027

Cited by 11 publications

(14 citation statements)

References 37 publications

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“…Our previous study showed that SLC5A7 is downregulated in the majority of CRC tissues and cells [ 30 ]. To further reveal the potential mechanism underlying the inactivation of SLC5A7 in CRC, two broad-spectrum demethylation chemicals DAC and AZA were utilized to treat HCT116 and RKO cells.…”

Section: Resultsmentioning

confidence: 99%

“…In our previous study, we demonstrated that the expression of SLC5A7 was involved in the p53 signaling pathway and stabilization of p53 [ 30 ]. The present results confirmed that the implementation of targeted demethylation was also associated with higher p53 and phosphor-p53 (ser 37) expression in cancer cells (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…However, mutant p53 actively promotes the development of cancer through gain-of-function activities [ 42 , 43 ]. And our previous study indicated that SLC5A7 had little effect on cancer cell proliferation in CRC cells expressing mutant p53 [ 30 ]. Thus, the potential therapeutic application of targeted demethylation of SLC5A7 may depend on p53 mutation status.…”

Section: Discussionmentioning

confidence: 99%

“…A study by Koepsell et al demonstrated that inhibitors of SLC5A1 and SLC5A2 that reduce glucose uptake have shown efficacy in the management of diabetes and cancer [ 29 ]. More importantly, our previous findings showed that SLC5A7 expression was decreased in CRC and positively correlated with prognosis [ 30 ]. However, the mechanisms underlying SLC5A7 downregulation and its role in CRC remain unclear.…”

Section: Introductionmentioning

confidence: 99%

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Targeted demethylation of the SLC5A7 promotor inhibits colorectal cancer progression

Liu

Yin

et al. 2022

Clin Epigenet

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Background SLC5A7 (solute carrier family 5 member 7), also known as choline transporter 1 (CHT1), is downregulated in colorectal cancer (CRC) and functions as a tumor suppressor. However, the mechanisms underlying the inactivation of SLC5A7 in CRC remain to be elucidated. Results In the present study, two broad-spectrum demethylation agents (azacitidine and decitabine) employed to treat CRC cells significantly upregulated SLC5A7 expression. Further results based on the CRC cohort and TCGA database indicated that SLC5A7 promoter methylation inversely correlated with SLC5A7 expression, and the status of SLC5A7 promotor methylation showed a promising prognostic value for patients with CRC. Next, the dCas9-multiGCN4/scFv-TET1CD-based precision demethylation system was constructed, which could significantly and specifically promote SLC5A7 expression in CRC cells through sgRNA targeting the SLC5A7 promoter. Both in vitro and in vivo experiments demonstrated that targeted demethylation of SLC5A7 by dCas9-multiGCN4/scFv-TET1CD-sgSLC5A7 inhibited tumor growth by stabilizing p53 and regulating downstream targets. Conclusions Collectively, DNA promoter methylation caused inactivation of SLC5A7 in CRC, and targeted demethylation of SLC5A7 might be a therapeutic target for CRC and other cancers.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Targeted demethylation of the SLC5A7 promotor inhibits colorectal cancer progression

Liu

Yin

et al. 2022

Clin Epigenet

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“…4 Conversely, some solute carrier proteins have been shown to inhibit colorectal cancer growth through related pathways. 5 SLC35 is a family of nucleotide sugar transporters that play a crucial role in connecting the synthesis of activated sugars in the nucleus or cytosol. 6 Among these transporters, SLC35C1, which is responsible for guanosine diphosphate fucose (GDP-fucose) transportation, has been shown to restrict the development of colorectal cancer.…”

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confidence: 99%

Solute carrier family 35 member D3 promotes colorectal cancer progression through AMPK signaling pathway

Wang,

Lu,

Zhang

et al. 2023

Precision Medical Sciences

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This article is aim to investigate the functional role and potential regulatory mechanisms of solute carrier family 35 member D3 (SLC35D3) in colorectal cancer. Beyond analyzing databases, western blot was used to detect and verify the expression of SLC35D3. Cell proliferation and invasion or migration ability were detected by CCK‐8, EdU, and Transwell assays. Animal experiments were conducted to verify if the biological function of SLC35D3 in vivo is consistent with that in vitro. Beyond SLC family pathway enrichment analysis, the relationship between SLC35D3 and metabolic pathway AMPK was explored using co‐immunoprecipitation and western blot. SLC35D3 is highly expressed in colorectal cancer (CRC) tissue. The overexpression or down regulation of SLC35D3 has been shown to promote or inhibit the biological functions of colorectal cancer, and similar experimental results can be verified in vivo experiments. Based on the high correlation between the SLC family and metabolic pathways, we chose the metabolic‐related AMPK pathway as the subject of our research. Co‐immunoprecipitation and protein analysis demonstrated that SLC35D3 may bind to AMPK molecules and regulate the AMPK pathway of colorectal cancer cells. Based on the above facts, SLC35D3 promotes colorectal cancer progression through regulating AMPK signaling pathway.

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CircFBXW4 Suppresses Colorectal Cancer Progression by Regulating the MiR‐338‐5p/SLC5A7 Axis

Song,

Fu,

et al. 2024

Advanced Science

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Dysregulated circular RNAs (circRNAs) contribute to tumourigenesis and cancer progression. However, the expression patterns and biological functions of circRNAs in colorectal cancer (CRC) remain elusive. Here, RNA sequencing and bioinformatics analyses are applied to screen for aberrantly expressed circRNAs. The expression of circFBXW4 in CRC tissues and cell lines is determined by quantitative real‐time PCR. A series of in vitro and in vivo biological function assays are implemented to assess the functions of circFBXW4. The regulatory mechanisms linking circFBXW4, miR‐338‐5p, and SLC5A7 are explored by western blotting, dual luciferase reporter assays, and RNA pull‐down assays. CircFBXW4 is dramatically downregulated in CRC tissues and cell lines. circFBXW4 downregulation is clearly correlated with malignant features and patient overall survival in CRC. Functionally, ectopic expression of circFBXW4 strikingly impairs the proliferation, migration, and invasion capacities of CRC cells in vitro and in vivo, whereas circFBXW4 knockdown has the opposite effects. Mechanistically, circFBXW4 competitively binds to miR‐338‐5p and prevents it from interacting with and repressing its target SLC5A7, thus suppressing the progression of CRC. This study reveals the specific critical role of circFBXW4 in inhibiting CRC progression via the miR‐338‐5p/SLC5A7 axis and provides an additional target for eradicating CRC.

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Choline-induced SLC5A7 impairs colorectal cancer growth by stabilizing p53 protein

Cited by 11 publications

References 37 publications

Targeted demethylation of the SLC5A7 promotor inhibits colorectal cancer progression

Targeted demethylation of the SLC5A7 promotor inhibits colorectal cancer progression

Solute carrier family 35 member D3 promotes colorectal cancer progression through AMPK signaling pathway

CircFBXW4 Suppresses Colorectal Cancer Progression by Regulating the MiR‐338‐5p/SLC5A7 Axis

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