The application of ApcMin/+ mouse model in colorectal tumor researches

Ren, Junlong; Sui, Hua; Fang, Fanfu; Li, Qi; Bai, Li

doi:10.1007/s00432-019-02883-6

Cited by 44 publications

(29 citation statements)

References 106 publications

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“…The mutation of the APC gene contributes to the abnormal activation of the Wnt/β‐catenin signalling pathway, which results in interference with the expression of multiple genes, initiating colorectal adenoma in Apc min/+ mice. 39 , 40 , 41 In this study, our data indicated that Rbm24 was significantly downregulated in intestinal tumour of Apc min/+ mice. Nevertheless, we did not find an association between RBM24 expression and APC mutation in human colorectal cancer tissues via bioinformatics analysis.…”

Section: Discussionsupporting

confidence: 59%

RNA‐binding protein RBM24 represses colorectal tumourigenesis by stabilising PTEN mRNA

Xia

Liu

et al. 2021

Clinical & Translational Med

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Background RNA‐binding motif protein 24 (RBM24) functions as a splicing regulator, which is critical for organ development and is dysregulated in human cancers. Here, we aim to uncover the biological function of RBM24 in colorectal tumourigenesis. Methods Xenograft tumour model, Rbm24 knockout and Apc min/+ mouse models were utilised. Colorectal cancer cells overexpressing or silencing RBM24 were established. RNA immunoprecipitation (RIP) assay was conducted to detect protein‐RNA associations. Gene expression was measured by immunohistochemistry, western blotting, or quantitative PCR (qPCR). Results Rbm24‐knockout mice developed spontaneous colorectal adenomas with lower expression of phosphatase and tensin homolog (PTEN). Immunohistochemical staining for the proliferation markers Ki‐67 and pHH3 and BrdU assay showed intestinal hyperplasia in Rbm24‐knockout mice compared to wild‐type mice. RBM24 expression in colorectal adenoma tissues of Apc min/+ mouse was downregulated compared with adjacent normal samples and was positively correlated with PTEN expression. In vitro, RBM24 overexpression suppressed cell proliferation, migration, invasion and increased sensitivity to 5‐FU or cisplatin in CRC cells. Mechanistically, RBM24 maintained PTEN mRNA stability by directly binding to the GT‐rich region at positions 8101–8251 in the 3′‐UTR of PTEN mRNA, prolonging the half‐life of PTEN mRNA, thereby increasing PTEN expression. Hence, low expression of RBM24 downregulated PTEN mRNA, causing the activation of PI3K‐Akt signalling in CRC cells. Furthermore, RBM24 expression in CRC tissues was lower than adjacent normal samples. RBM24 expression was positively correlated with PTEN expression and negatively correlated with Ki‐67 level. CRC patients with high RBM24 expression had a favourable outcome. Conclusions Taken together, RBM24 expression is markedly lower in colorectal tumours than in para‐carcinoma tissues. Rbm24‐knockout mice develop spontaneous colorectal adenomas. RBM24 directly binds and stabilises PTEN mRNA, which could cause the suppression of CRC cell proliferation, migration and invasion, thereby repressing colorectal tumourigenesis. These findings support the tumour‐suppressive role of RBM24. Targeting RBM24 holds strong promise for the diagnosis and treatment of CRC.

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Section: Discussionsupporting

confidence: 59%

RNA‐binding protein RBM24 represses colorectal tumourigenesis by stabilising PTEN mRNA

Xia

Liu

et al. 2021

Clinical & Translational Med

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“…Coincidently, Tregs have also been reported by clinical observations and mechanistic studies, to play an indispensable role as a promoter of tumor growth because of its suppressive effects on the autologous effector T-cell responses. However, others found that Tregs may inhibit the intestinal tumor growth in adenomatous polyposis coli (Apc)-mice [62,63]. Nonetheless, in the early stages of tumor development, it is widely understood that the balance of lymphocyte-recruiting chemokines is altered, possibly contributing to the observed shift toward higher abundance of Treg.…”

Section: Discussionmentioning

confidence: 99%

YYFZBJS ameliorates colorectal cancer progression in ApcMin/+ mice by remodeling gut microbiota and inhibiting regulatory T-cell generation

Sui

Zhang

et al. 2020

Cell Commun Signal

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Background: Progression of Colorectal cancer (CRC) is influenced by single or compounded environmental factors. Accumulating evidence shows that microbiota can influence the outcome of cancer immunotherapy. T cell, one of the main populations of effector immune cells in antitumor immunity, has been considered as a double-edged sword during the progression of CRC. Our previous studies indicate that traditional Chinese herbs (TCM) have potential anticancer effects in improving quality of life and therapeutic effect. However, little is known about the mechanism of TCM formula in cancer prevention. Methods: Here, we used C57BL/6 J Apc Min/+ mice, an animal model of human intestinal tumorigenesis, to investigate the gut bacterial diversity and their mechanisms of action in gastrointestinal adenomas, and to evaluate the effects of Yi-Yi-Fu-Zi-Bai-Jiang-San (YYFZBJS) on of colon carcinogenesis in vivo and in vitro. Through humaninto-mice fecal microbiota transplantation (FMT) experiments from YYFZBJS volunteers or control donors, we were able to differentially modulate the tumor microbiome and affect tumor growth as well as tumor immune infiltration.

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“…2) (Stastna et al 2019). An inconvenience of this model is that, unlike human CRC, the majority of mice polyps appear in the small intestine, and mice die early by day 120 (De-Souza & Costa-Casagrande 2018, Ren et al 2019.…”

Section: Crc Modelsmentioning

confidence: 99%

Metabolic and hormonal remodeling of colorectal cancer cell signaling by diabetes

Gutiérrez-Salmerón

Lucena

Chocarro-Calvo

et al. 2021

Endocrine-Related Cancer

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The existence of molecular links that facilitate colorectal cancer (CRC) development in the population with type 2 diabetes (T2D) is supported by substantial epidemiological evidence. This review summarizes how the systemic metabolic and hormonal imbalances from T2D alter CRC cell metabolism, signaling and gene expression as well as their reciprocal meshing, with an overview of CRC molecular subtypes and animal models to study the diabetes-CRC cancer links. Metabolic and growth factor checkpoints ensure a physiological cell proliferation rate compatible with limited nutrient supply. Hyperinsulinemia and hyperleptinemia in prediabetes and excess circulating glucose and lipids in T2D, overcome formidable barriers for tumor development. Increased nutrient availability favours metabolic reprogramming, alters signaling and generate mutations and epigenetic modifications, through increased reactive oxygen species and oncometabolites. The reciprocal control between metabolism and hormone signaling is lost in diabetes. Excess adipose tissue at the origin of T2D, unbalances adipokine (leptin / adiponectin) secretion ratios and function and disrupts the Insulin/IGF axes. Leptin/adiponectin imbalances in T2D are believed to promote proliferation and invasion of CRC cancer cells and contribute to inflammation, an important component of CRC tumorigenesis. Disruption of the Insulin/IGF axes in T2D targets systemic and CRC cell metabolic reprogramming, survival and proliferation. Future research to clarify the molecular diabetes-CRC links will help to prevent CRC and reduce its incidence in the diabetic population and must guide therapeutic decisions.

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The application of ApcMin/+ mouse model in colorectal tumor researches

Cited by 44 publications

References 106 publications

RNA‐binding protein RBM24 represses colorectal tumourigenesis by stabilising PTEN mRNA

RNA‐binding protein RBM24 represses colorectal tumourigenesis by stabilising PTEN mRNA

YYFZBJS ameliorates colorectal cancer progression in ApcMin/+ mice by remodeling gut microbiota and inhibiting regulatory T-cell generation

Metabolic and hormonal remodeling of colorectal cancer cell signaling by diabetes

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