GABA-producing Lactobacillus plantarum inhibits metastatic properties and induces apoptosis of 5-FU-resistant colorectal cancer cells via GABAB receptor signaling

An, JaeJin; Seok, Heon; Ha, Eun-Mi

doi:10.1007/s12275-021-0562-5

Cited by 36 publications

(20 citation statements)

References 40 publications

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“…Numerous studies have shown that adjuvant 5-FU-based chemotherapy can improve the 5-year overall survival (OS) of stage II and III patients compared to surgery alone ( 41 , 42 ). However, the prognosis of such patients still remains poor, mainly due to 5-FU resistance ( 43 , 44 ). Herein, we have made several novel observations.…”

Section: Discussionmentioning

confidence: 99%

Restoring HOXD10 Exhibits Therapeutic Potential for Ameliorating Malignant Progression and 5-Fluorouracil Resistance in Colorectal Cancer

Pan

Wang

et al. 2021

Front. Oncol.

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Emerging evidence suggests that hypermethylation of HOXD10 plays an important role in human cancers. However, the biological and clinical impacts of HOXD10 overmethylation and its downstream targets in colorectal cancer remain unknown. We evaluated the methylation level of HOXD10 in paired cancer and normal tissues (n = 42) by using pyrosequencing, followed by validation of the methylation status of HOXD10 from The Cancer Genome Atlas (TCGA) datasets with 302 cancer tissues and 38 normal tissues. The biological function of HOXD10 was characterized in cell lines. We further evaluated the effects of HOXD10 and its targets on chemoresistance in our established resistant cell lines and clinical cohort (n = 66). HOXD10 was found frequently methylated in colorectal cancer, and its hypermethylation correlates with its low expression level, advanced disease, and lymph node metastasis. Functionally, HOXD10 acts as a tumor suppressor gene, in which HOXD10-expressing cells showed suppressed cell proliferation, colony formation ability, and migration and invasion capacity. Mechanistically, DNMT1, DNMT3B, and MeCP2 were recruited in the HOXD10 promoter, and demethylation by 5-Aza-2′-deoxycytidine (5-Aza-CdR) treatment or MeCP2 knockdown can sufficiently induce HOXD10 expression. HOXD10 regulates the expressions of miR-7 and IGFBP3 in a promoter-dependent manner. Restoration of the expression of HOXD10 in 5-fluorouracil (5-FU)-resistant cells significantly upregulates the expressions of miR-7 and IGFBP3 and enhances chemosensitivity to 5-FU. In conclusion, we provide novel evidence that HOXD10 is frequently methylated, silenced, and contributes to the development of colorectal cancers. Restoration of HOXD10 activates the expressions of miR-7 and IGFBP3 and results in an inhibited phenotype biologically, suggesting its potential therapeutic relevance in colorectal cancer (CRC).

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Section: Discussionmentioning

confidence: 99%

Restoring HOXD10 Exhibits Therapeutic Potential for Ameliorating Malignant Progression and 5-Fluorouracil Resistance in Colorectal Cancer

Pan

Wang

et al. 2021

Front. Oncol.

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“…Several Lactobacillus species produce a wide range of neurotransmitters (Yong et al, 2019) (Table 2). GABA can be synthesized by certain Bifidobacterium species (Barrett et al, 2012), Bacteroides fragilis (Strandwitz et al, 2019), and L. plantarum (An et al, 2021). Furthermore, microbial species, including L. plantarum, B. subtilis, and S. aureus, can produce Ach (Horiuchi et al, 2003;Koussoulas et al, 2018;O'Donnell et al, 2020).…”

Section: Neurotransmittersmentioning

confidence: 99%

Gut microbiota: Linking nutrition and perinatal depression

Song

Kan³

et al. 2022

Front. Cell. Infect. Microbiol.

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Perinatal depression is a mood disorder that is reported in women during pregnancy (prenatal) and after childbirth (postnatal). The onset of perinatal depression is associated with changes in reproductive hormones, stress hormones and neurosteroids. These chemical compounds can be modulated by the gut microbiota, which may affect maternal mental health during the perinatal period via the gut-brain-axis. Recent studies suggest that nutritional and dietary interventions (vitamin D, ω-3 fatty acids, iron, and fiber) effectively prevent or mitigate maternal depression and anxiety, but their efficacy is confounded by various factors, including the gut microbiota. Probiotics are efficacious in maintaining microbiota homeostasis, and thus, have the potential to modulate the development of perinatal mood disorders, despite no evidence in human. Therefore, clinical trials are warranted to investigate the role of probiotic supplementation in perinatal depression and behavioral changes. This article reviews the interplay between nutrition, gut microbiota and mood and cognition, and the evidence suggesting that probiotics affect the onset and development of perinatal depression.

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“…Moreover, Lactobacillus was more abundant in CRC patients with PIK3CA mutations in our study. Lactobacillus inhibits the growth of colorectal cancer by secreting short-chain fatty acids (SCFAs) that enhance the intestinal barrier function [ 32 ]. Taken together, our findings are supported by the above-mentioned reports, which highlight the clinical relevance of Faecalibacterium and Lactobacillus in the development of CRC and suggest their potential to become a therapeutic agent by producing bioactive compounds that may benefit the host.…”

Section: Discussionmentioning

confidence: 99%

A comprehensive analysis of the microbiota composition and host driver gene mutations in colorectal cancer

Yuan

Tao

Wang³

et al. 2022

Invest New Drugs

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Studies of both, microbiota and target therapy associated with gene mutations in colorectal cancer, (CRC) have attracted increasing attention. However, only a few of them analyzed the combined effects on CRC. we analyzed differences in intestinal microbiota of 44 colorectal cancer patients and 20 healthy controls (HC) using 16S rRNA gene sequencing of fecal samples. For 39 of the CRC patients, targeted Next Generation Sequencing (NGS) was carried out at formalin fixed paraffin embedded (FFPE) samples to identify somatic mutation profiles. Compared to the HC group, the microbial diversity of CRC patients was significantly lower. In the CRC group, we found a microbiome that was significantly enriched for strains of Bifidobacterium, Bacteroides, and Megasphaera whereas in the HC group the abundance of Collinsella, Faecalibacterium, and Agathobacter strains was higher. Among the mutations detected in the CRC group, the APC gene had the highest mutation rate (77%, 30/39). We found that the KRAS mutant type was closely associated with Faecalibacterium, Roseburia, Megamonas, Lachnoclostridium, and Harryflintia. Notably, Spearman correlation analysis showed that KRAS mutations were negatively correlated with the existence of Bifidobacterium and positively correlated with Faecalibacterium. By employing 16S rRNA gene sequencing, we identified more unique features of microbiota profiles in CRC patients. For the first time, our study showed that gene mutations could directly be linked to the microbiota composition of CRC patients. We hypothesize that the effect of a targeted colorectal cancer therapy is also closely related to the colorectal flora, however, this requires further investigation.

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GABA-producing Lactobacillus plantarum inhibits metastatic properties and induces apoptosis of 5-FU-resistant colorectal cancer cells via GABAB receptor signaling

Cited by 36 publications

References 40 publications

Restoring HOXD10 Exhibits Therapeutic Potential for Ameliorating Malignant Progression and 5-Fluorouracil Resistance in Colorectal Cancer

Restoring HOXD10 Exhibits Therapeutic Potential for Ameliorating Malignant Progression and 5-Fluorouracil Resistance in Colorectal Cancer

Gut microbiota: Linking nutrition and perinatal depression

A comprehensive analysis of the microbiota composition and host driver gene mutations in colorectal cancer

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