Expression of DNA methyltransferases and target microRNAs in human tissue samples related to sporadic colorectal cancer

Huang, Chao; Liu, Hong; Gong, Xiaohua; Wu, Liyun; Wen, Bin

doi:10.3892/or.2016.5104

Cited by 11 publications

(9 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On the other hand, ROCK1 overexpression is associated with colorectal cancer (CRC) [66,67]. Moreover, microRNA-148a and microRNA-21 inhibit DNA methyltransferase 1 (DNMT1) [68], an oncogene which is also overexpressed in CRC [69][70][71]. Indeed, incubation of CRC cells (Lim 1215) with human milk exosomes increased the cellular content of microRNA-148a [5], and addition of milk exosomes to normal intestinal cells (CRL 1831) significantly decreased DNMT1 expression [5,24].…”

Section: Discussionmentioning

confidence: 99%

Milk Exosomes Prevent Intestinal Inflammation in a Genetic Mouse Model of Ulcerative Colitis: A Pilot Experiment

Stremmel¹,

Weiskirchen

Melnik

2020

Inflamm Intest Dis

View full text Add to dashboard Cite

Background: Milk is rich in nutrients and anabolic mediators rendering it essential for postnatal growth and metabolic programming. However, in adults, excessive consumption of milk is controversial as civilization disorders such as diabetes or prostate cancer may be promoted. A cytoprotective effect of milk could be utilized in inflammatory conditions, that is, chronic colitis. Objective: To evaluate the effect of bovine milk exosomes on intestinal inflammation in a genetic mouse model of ulcerative colitis. Methods: Intestinal-specific kindlin 2 knockout (KO) mice were exposed for 4 days to tamoxifen for induction of an ulcerative colitis phenotype. At the same time 4 other kindlin 2 KO mice were exposed to 33 μg/g cow milk derived exosomes in PBS by oral gavage. Both groups were compared to untreated wild-type controls. Results: Milk exosomes prevented the appearance of a severe ulcerative phenotype. The macroscopic colitis score dropped from a mean of 3.33 in untreated mice to 0.75 index points (p < 0.01) in exosome-treated mice, which included significant improvement of the subscores of stool improvement and colon weight and length. Treated mice featured a noninflamed appearance of the intestinal mucosa. Key Message: Milk exosomes have cytoprotective/anti-inflammatory activity in a genetic mouse model of ulcerative colitis. The mechanisms behind this need to be elucidated. This pilot study needs verification before a therapeutic strategy is developed.

show abstract

Section: Discussionmentioning

confidence: 99%

Milk Exosomes Prevent Intestinal Inflammation in a Genetic Mouse Model of Ulcerative Colitis: A Pilot Experiment

Stremmel¹,

Weiskirchen

Melnik

2020

Inflamm Intest Dis

View full text Add to dashboard Cite

show abstract

“…The protein content and size of bovine milk exosomes was significantly reduced in fermented cow's milk associated with a substantial loss of miRs (miR-29b, miR-21) compared to unfermented raw milk [48]. Malignant epithelial cells of CRC exhibit a reduced Melnik and Schmitz J Transl Med (2019) 17:3 expression of miR-148a [267][268][269][270], which increases the expression of DNMT1 that functions as a tumor promoter in CRC [271][272][273]. Intriguingly, Golan-Gerstl et al [44] demonstrated that the incubation of CRC cells (Lim 1215) with human breastmilk exosomes increased the cellular content of miR-148a.…”

Section: Colorectal Cancermentioning

confidence: 99%

Exosomes of pasteurized milk: potential pathogens of Western diseases

Melnik

Schmitz

2019

J Transl Med

View full text Add to dashboard Cite

Milk consumption is a hallmark of western diet. According to common believes, milk consumption has beneficial effects for human health. Pasteurization of cow's milk protects thermolabile vitamins and other organic compounds including bioactive and bioavailable exosomes and extracellular vesicles in the range of 40-120 nm, which are pivotal mediators of cell communication via systemic transfer of specific micro-ribonucleic acids, mRNAs and regulatory proteins such as transforming growth factor-β. There is compelling evidence that human and bovine milk exosomes play a crucial role for adequate metabolic and immunological programming of the newborn infant at the beginning of extrauterine life. Milk exosomes assist in executing an anabolic, growth-promoting and immunological program confined to the postnatal period in all mammals. However, epidemiological and translational evidence presented in this review indicates that continuous exposure of humans to exosomes of pasteurized milk may confer a substantial risk for the development of chronic diseases of civilization including obesity, type 2 diabetes mellitus, osteoporosis, common cancers (prostate, breast, liver, B-cells) as well as Parkinson's disease. Exosomes of pasteurized milk may represent new pathogens that should not reach the human food chain.

show abstract

“…Previously, we illustrated that the expression of DNMT1 was significantly higher in GC tissues than in non-GC tissues by meta-analysis[8]. Simultaneously, several studies have also revealed that DNMT1 was strongly expressed in GC and CRC[9,10], suggesting that DNMT1 could be a potential biomarker in screening of GI cancer.…”

Section: Introductionmentioning

confidence: 96%

Protein expression trends of DNMT1 in gastrointestinal diseases: From benign to precancerous lesions to cancer

Sun

Dong

et al. 2019

WJGO

View full text Add to dashboard Cite

BACKGROUNDIn recent years, the incidence of gastrointestinal (GI) cancer in China has increased annually. Early detection and appropriate therapy are considered to be the key to treat GI cancer. DNMT1 takes an active part in the advancement of GI cancer, which will change as the disease progresses. But its expression characteristics in the dynamic variations of GI carcinogenesis are still unclear.AIMTo investigate the expression characteristics of DNMT1 in different GI diseases.METHODSWe detected the expression of DNMT1 in 650 cases of different GI diseases by immunohistochemistry, including 90 cases of chronic superficial gastritis (CSG), 72 cases of atrophic gastritis with intestinal metaplasia (AG/GIM), 54 cases of low-grade intraepithelial neoplasia (GLIN), 66 cases of high-grade intraepithelial neoplasia (GHIN), 71 cases of early gastric cancer (EGC), 90 cases of normal intestinal mucosa (NIM), 54 cases of intestinal low-grade intraepithelial neoplasia (ILIN), 71 cases of intestinal high-grade intraepithelial neoplasia (IHIN), and 82 cases of early colorectal cancer (ECRC).RESULTSIn the CSG group, all cases showed weakly positive or negative expression of DNMT1. However, in other four groups (AG/GIM, GLIN, GHIN, and EGC), the positive expression rate gradually increased with the severity of the diseases; the negative or weakly positive cases accounted for 55.56% (40/72), 38.89% (21/54), 1.52% (1/66), and 1.41% (1/71), respectively. Besides, the moderately positive cases were 44.44% (32/72), 57.41% (31/54), 80.30% (53/66), and 43.66% (31/71), respectively. The strongly positive cases only existed in the GLIN (3.70%, 2/54), GHIN (18.18%, 12/66), and EGC (54.93%, 39/71) groups. The differences between any two groups were statistically significant (P < 0.05). Similarly, in the NIM group, cases with weakly positive expression of DNMT1 were predominant (91.11%, 82/90), and the rest were moderately positive cases (8.89%, 8/90). In the ILIN, IHIN, and ECRC groups, the rates of cases with weak or negative expression of DNMT1 were 46.30% (25/54), 12.68% (9/71), and 4.88% (4/82), respectively; with moderately positive expression were 53.70% (29/54), 71.83% (51/71), and 34.15% (28/82), respectively; and with strongly positive expression were 0.00% (0/54), 15.49% (11/71), and 60.98% (50/82), respectively. The differences between any two groups were also statistically significant (P < 0.05).CONCLUSIONThe overexpression of DNMT1 protein could effectively predict early GI cancers and severe precancerous lesions, which may have potential clinical application value.

show abstract

Expression of DNA methyltransferases and target microRNAs in human tissue samples related to sporadic colorectal cancer

Cited by 11 publications

References 51 publications

Milk Exosomes Prevent Intestinal Inflammation in a Genetic Mouse Model of Ulcerative Colitis: A Pilot Experiment

Milk Exosomes Prevent Intestinal Inflammation in a Genetic Mouse Model of Ulcerative Colitis: A Pilot Experiment

Exosomes of pasteurized milk: potential pathogens of Western diseases

Protein expression trends of DNMT1 in gastrointestinal diseases: From benign to precancerous lesions to cancer

Contact Info

Product

Resources

About