Pten gene deletion in intestinal epithelial cells enhances susceptibility to Salmonella Typhimurium infection in mice

Howe, Cody; Mitchell, Jonathon; Kim, Su Jin; Rhee, Sang Hoon

doi:10.1007/s12275-019-9320-3

Cited by 9 publications

(8 citation statements)

References 31 publications

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“…To confirm this speculation, we found that there was a binding region between GAS5 and miR-23a through RNA pull-down assay and dual-luciferase reporter gene assay (Figures 6F,G). It has been reported that PTEN gene deletion can enhance the sensitivity of mice to ST infection (Howe et al, 2019). In addition, we predicted through the biological websites that miR-23a has multiple target genes, including PTEN.…”

Section: Lncrna Gas5 Competitively Bound To Mir-23a To Upregulate Ptementioning

confidence: 94%

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Chlorogenic Acid Promotes Autophagy and Alleviates Salmonella Typhimurium Infection Through the lncRNAGAS5/miR-23a/PTEN Axis and the p38 MAPK Pathway

Tan

Fang

et al. 2020

Front. Cell Dev. Biol.

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Background: Salmonella typhimurium (ST) causes several intestinal diseases. Polyphenols including chlorogenic acid (CGA) inhibit pathogenesis. Objective: This study aimed to investigate the mechanisms of CGA in ST infection. Methods: The intestinal pathological changes and survival rate of ST-infected mice were measured to verify the protection of CGA on ST infection. The antibacterial effects of CGA in vitro on the invasion to intestinal epithelial cells and autophagy was evaluated. The relationships among GAS5, miR-23a, and PTEN were verified. Expression of inflammation-and autophagy-related proteins was detected. Results: CGA treatment alleviated pathological damage, improved the secretion disturbance of intestinal cytokines caused by ST infection, and reduced the mortality of mice. Intestinal GAS5 was upregulated after CGA treatment. LncRNA GAS5 competitively bound to miR-23a to upregulate PTEN and inhibit the p38 MAPK pathway. CGA regulated the p38 MAPK pathway through lncRNA GAS5/miR-23a/PTEN axis to promote autophagy in ST infection. The functional rescue experiments of miR-23a and PTEN further identified these effects. Conclusion: CGA promotes autophagy and inhibits ST infection through the GAS5/miR-23a/PTEN axis and the p38 MAPK pathway.

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Section: Lncrna Gas5 Competitively Bound To Mir-23a To Upregulate Ptementioning

confidence: 94%

“…The expression of miR-23a in intestinal tissues of ST-infected mice treated with CGA was significantly downregulated. Additionally, PTEN gene deletion can enhance the sensitivity of mice to ST infection (Howe et al, 2019). miR-23a has multiple target genes, including PTEN.…”

Section: The Cerna Network Of Gas5/mir-23a/ Ptenmentioning

confidence: 99%

Chlorogenic Acid Promotes Autophagy and Alleviates Salmonella Typhimurium Infection Through the lncRNAGAS5/miR-23a/PTEN Axis and the p38 MAPK Pathway

Tan

Fang

et al. 2020

Front. Cell Dev. Biol.

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“…To study the impact of CRHR-mediated responses in colon cancer, we utilized the Apcmin/+ mouse model of intestinal epithelial tumorigenesis, in which tumor development occurs mainly in the small intestine [17,18]. Specifically, Crhr1 −/− and Crhr2 −/− mice were combined with Apcmin/+ mice to generate Apcmin/+; Crhr1 −/− mice and Apcmin/+; Crhr2 −/− mice, respectively.…”

Section: Loss Of Crhr2 Gene Promotes Tumor Development In the Apcmin/mentioning

confidence: 99%

“…Thus, the Apcmin/+ mouse has been widely utilized as an animal model of human colon cancer. However, Apcmin/+ mice develop tumors predominately in the small intestine [17,18], while human FAP patients develop polyps in their colon and rectum [23]. To reconcile this discrepancy between the Apcmin/+ mouse model and human colon cancer patients, it is necessary to examine whether CRHR1-or CRHR2-mediated responses would result in a similar effect in a different mouse model of colon cancer.…”

Section: Crhr2 Deficiency Promotes Tumor Development and Growth In Thmentioning

confidence: 99%

Corticotropin-Releasing Hormone Receptor Alters the Tumor Development and Growth in Apcmin/+ Mice and in a Chemically-Induced Model of Colon Cancer

Lee

Elise²,

Patel

et al. 2021

IJMS

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The neuroendocrine circuit of the corticotropin-releasing hormone (CRH) family peptides, via their cognate receptors CRHR1 and CRHR2, copes with psychological stress. However, peripheral effects of the CRH system in colon cancer remains elusive. Thus, we investigate the role of CRHR1 and CRHR2 in colon cancer. Human colon cancer biopsies were used to measure the mRNA levels of the CRH family by quantitative real-time PCR. Two animal models of colon cancer were used: Apcmin/+ mice and azoxymethane (AOM)/dextran sulfate sodium (DSS)-treated mice. The mRNA levels of CRHR2 and UCN III are reduced in human colon cancer tissues compared to those of normal tissues. Crhr1 deletion suppresses the tumor development and growth in Apcmin/+ mice, while Crhr2 deficiency exacerbates the tumorigenicity. Crhr1 deficiency not only inhibits the expression of tumor-promoting cyclooxygenase 2, but also upregulates tumor-suppressing phospholipase A2 in Apcmin/+ mice; however, Crhr2 deficiency does not change these expressions. In the AOM/DSS model, Crhr2 deficiency worsens the tumorigenesis. In conclusion, Crhr1 deficiency confers tumor-suppressing effects in Apcmin/+ mice, but Crhr2 deficiency worsens the tumorigenicity in both Apcmin/+ and AOM/DSS-treated mice. Therefore, pharmacological inhibitors of CRHR1 or activators of CRHR2 could be of significance as anti-colon cancer drugs.

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“…The loss or mutation of PTEN causes constitutive activation of the PI3K-induced pathway, which eventually leads to tumor development [ 27 , 28 , 29 ]. In addition to its classical role as a tumor suppressor, PTEN is also considered an immune regulator involved in inflammatory responses [ 30 , 31 , 32 , 33 , 34 ]. In mammals, it has been demonstrated that miRNAs regulate cell apoptosis, proliferation, and autophagy by targeting PTEN [ 35 , 36 , 37 ].…”

Section: Introductionmentioning

confidence: 99%

Phosphatase and Tensin Homolog (PTEN) of Japanese Flounder—Its Regulation by miRNA and Role in Autophagy, Apoptosis and Pathogen Infection

Guan

Sun

2020

IJMS

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MicroRNAs (miRNAs) are small non-coding RNAs with important roles in diverse biological processes including immunity. Japanese flounder (Paralichthys olivaceus) is an aquaculture fish species susceptible to the infection of bacterial and viral pathogens including Edwardsiella tarda. In a previous study, pol-miR-novel_547, a novel miRNA of flounder with unknown function, was found to be induced by E. tarda. In the present study, we investigated the regulation and function of pol-miR-novel_547 and its target gene. We found that pol-miR-novel_547 was regulated differently by E. tarda and the viral pathogen megalocytivirus, and pol-miR-novel_547 repressed the expression of PTEN (phosphatase and tensin homolog) of flounder (PoPTEN). PoPTEN is ubiquitously expressed in multiple tissues of flounder and responded to bacterial and viral infections. Interference with PoPTEN expression in flounder cells directly or via pol-miR-novel_547 promoted E. tarda invasion. Consistently, in vivo knockdown of PoPTEN enhanced E. tarda dissemination in flounder tissues, whereas in vivo overexpression of PoPTEN attenuated E. tarda dissemination but facilitated megalocytivirus replication. Further in vitro and in vivo studies showed that PoPTEN affected autophagy activation via the AKT/mTOR pathway and also modulated the process of apoptosis. Together these results reveal for the first time a critical role of fish PTEN and its regulatory miRNA in pathogen infection, autophagy, and apoptosis.

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Pten gene deletion in intestinal epithelial cells enhances susceptibility to Salmonella Typhimurium infection in mice

Cited by 9 publications

References 31 publications

Chlorogenic Acid Promotes Autophagy and Alleviates Salmonella Typhimurium Infection Through the lncRNAGAS5/miR-23a/PTEN Axis and the p38 MAPK Pathway

Chlorogenic Acid Promotes Autophagy and Alleviates Salmonella Typhimurium Infection Through the lncRNAGAS5/miR-23a/PTEN Axis and the p38 MAPK Pathway

Corticotropin-Releasing Hormone Receptor Alters the Tumor Development and Growth in Apcmin/+ Mice and in a Chemically-Induced Model of Colon Cancer

Phosphatase and Tensin Homolog (PTEN) of Japanese Flounder—Its Regulation by miRNA and Role in Autophagy, Apoptosis and Pathogen Infection

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