Changes of microRNAs-192, 196a and 203 correlate with Barrett's esophagus diagnosis and its progression compared to normal healthy individuals

Lužná, Pavla; Gregar, Jan; Überall, Ivo; Radová, Lenka; Procházka, Vladimír; Ehrmann, Jiří

doi:10.1186/1746-1596-6-114

Cited by 41 publications

(36 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We additionally showed that miR-192 can suppress expression of the bile acid and anticancer drug transporter OATP1B3 and the bile acid transporter OST␣/␤ in a FXR-dependent manner. It remains unclear whether restoration of miR-192 expression and the consequently diminished expression of FXR target genes would be beneficial for cancer patients, especially considering that miR-192 has been shown to possibly act as an oncogenic miRNA by downregulation of Smad interacting protein 1 in other inflammation-related cancers (21,26,35). Therefore, it can be speculated that diminished expression of the transport protein OST␣/OST␤, a heterodimer-forming bile acid transporter important for the excretion of bile acids from hepatocytes and enterocytes, may be a mechanism of intracellular bile acid accumulation promoting inflammation and/or cancer development in certain cases.…”

Section: Discussionmentioning

confidence: 99%

“…An important role of miR-192 targeting ZEB2 mRNA has also been found in HCC (13). In contrast, certain forms of cancer, such as cholangiocarcinoma and esophageal cancer, show increased miR-192 expression during carcinogenesis (21,26).…”

mentioning

confidence: 95%

“…Elevated serum levels of miR-192 have been detected in various liverassociated diseases, including drug-induced liver injury, nonalcoholic steatohepatitis, cholangiocarcinoma, and hepatitis B-related hepatocellular carcinoma and may serve as a biomarker (24,26,28,31,37). Thus several studies have hypothesized that tissue-specific chronic inflammation may trigger increases in miR-192 expression, as in nonalcoholic steatohepatitis (21,24,26). Because miR-192 shows an inverse correlation with the metastatic potential of colon cancer cells, miR-192 has been suggested to be a predictive biomarker for the risk of developing liver metastasis in colon carcinoma.…”

mentioning

confidence: 96%

See 2 more Smart Citations

microRNA-192 suppresses the expression of the farnesoid X receptor

Krattinger

Boström

Schiöth

et al. 2016

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

Farnesoid X receptor (FXR, NR1H4) plays an important role in the regulation of bile acid homeostasis in liver and intestine and may exert protective effects against certain forms of cancer such as colon carcinoma. However, the role of FXR in cell growth regulation, apoptosis, and carcinogenesis is still controversial. Similar to FXR, microRNA-192 (miR-192) is mainly expressed in the liver and colon and plays an important role in the pathogenesis of colon carcinoma. In this study, we investigated the extent to which FXR is regulated by miR-192. Two in silico-predicted binding sites for miR-192-3p within the NR1H4-3' untranslated region (UTR) were examined in vitro by luciferase reporter assays. Wild-type and mutated forms of the NR1H4-3'UTR were subcloned into a pmirGLO vector and cotransfected into Huh-7 cells with miR-192-3p. To study the effects of miR-192 on the expression of FXR, FXR target genes and cell proliferation, Huh-7 and Caco-2 cells were transfected with miR-192-5p and -3p mimics or antagomirs. In addition, the correlation between FXR and miR-192 expression was studied by linear regression analyses in colonic adenocarcinoma tissue from 27 patients. MiR-192-3p bound specifically to the NR1H4-3'UTR and significantly decreased luciferase activity. Transfection with miR-192 led to significant decreases in NR1H4 mRNA and protein levels as well as the mRNA levels of the FXR-inducible bile acid transporters OSTα-OSTβ and OATP1B3. Significant inverse correlations were detected in colonic adenocarcinoma between NR1H4 mRNA and miR-192-3p expression. In summary, microRNA-192 suppresses the expression of FXR and FXR target genes in vitro and in vivo.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 95%

mentioning

confidence: 96%

See 1 more Smart Citation

microRNA-192 suppresses the expression of the farnesoid X receptor

Krattinger

Boström

Schiöth

et al. 2016

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

show abstract

“…Up‐regulation of “oncomir” miR‐192 has been previously linked to GERD 53, 54 and associated with supraglottic laryngeal cancer and metastasis 15…”

Section: Discussionmentioning

confidence: 99%

NF‐κB inhibition reverses acidic bile‐induced miR‐21, miR‐155, miR‐192, miR‐34a, miR‐375 and miR‐451a deregulations in human hypopharyngeal cells

Doukas¹,

Vageli²,

Sasaki³

2018

J Cellular Molecular Medi

View full text Add to dashboard Cite

We previously demonstrated that acidic bile activates NF‐κB, deregulating the expression of oncogenic miRNA markers, in pre‐malignant murine laryngopharyngeal mucosa. Here, we hypothesize that the in vitro exposure of human hypopharyngeal cells to acidic bile deregulates cancer‐related miRNA markers that can be reversed by BAY 11‐7082, a pharmacologic NF‐κB inhibitor. We repetitively exposed normal human hypopharyngeal primary cells and human hypopharyngeal keratinocytes to bile fluid (400 μmol/L), at pH 4.0 and 7.0, with/without BAY 11‐7082 (20 μmol/L). We centred our study on the transcriptional activation of oncogenic miR‐21, miR‐155, miR‐192, miR‐34a, miR‐375, miR‐451a and NF‐κB‐related genes, previously linked to acidic bile‐induced pre‐neoplastic events. Our novel findings in vitro are consistent with our hypothesis demonstrating that BAY 11‐7082 significantly reverses the acidic bile‐induced oncogenic miRNA phenotype, in normal hypopharyngeal cells. BAY 11‐7082 strongly inhibits the acidic bile‐induced up‐regulation of miR‐192 and down‐regulation of miR‐451a and significantly decreases the miR‐21/375 ratios, previously related to poor prognosis in hypopharyngeal cancer. This is the first in vitro report that NF‐κB inhibition reverses acidic bile‐induced miR‐21, miR‐155, miR‐192, miR‐34a, miR‐375 and miR‐451a deregulations in normal human hypopharyngeal cells, suggesting that acidic bile‐induced events are directly or indirectly dependent on NF‐κB signalling.

show abstract

“…Additional studies have indicated that 70% of patients already present with tumor metastases when clinical symptoms first appeared, and with a cervical lymph node metastatic rate of 73.0% to 74.5% [7]. In significant number of cases Barrett's esophagus develops to esophageal adenocarcinoma [8]. …”

Section: Discussionmentioning

confidence: 99%

ABCG2/V-ATPase was associated with the drug resistance and tumor metastasis of esophageal squamous cancer cells

Huang

Lü

et al. 2012

Diagn Pathol

View full text Add to dashboard Cite

BackgroundATP-binding cassette sub-family G member 2 (ABCG2) is a protein that in humans is encoded by the ABCG2 gene. ABCG2 participates in efflux of many chemotherapeutic agents. ABCG2 is often expressed in hematopoietic progenitor or stem cells. Vacuolar-H + −ATPase (V-ATPase) plays a key role in adjusting and maintaining intracellular pH and in regulating the drug tolerance of cells. The TNM Classification of Malignant Tumours (TNM) is a cancer staging system that describes the extent of cancer in a patient’s body. In this study, the expression of ABCG2 and V-ATPase in esophageal squamous cancer cells was detected.MethodsImmunohistochemistry staining and Immunofluorescence double staining were used to detect the expression of ABCG2 and V-ATPase in in 66 cases of esophageal squamous cancer cells. Associations and differences in expression of ABCG2 with that of V-ATPase were analyzed.ResultsPositive staining patterns for both ABCG2 (66.67%) and V-ATPase (68.18%) were located mainly in the plasma membrane and cytoplasm. Marked differences in expression were also shown (P < 0.001) among 3 groups of pathological grades and TNM stages in these carcinomas. Marked differences were also found for ABCG2 expression between the two groups in the pathological grades and in the TNM staging groups (P < 0.01), but not between the αb and βgroups. V-ATPase expression was statistically significant between the 2 groups in the pathological grades and TNM stages (P < 0.05). This was not evident between α and β groups of pathological grades or between αb and βof the TNM stages. Marked differences in expression of ABCG2 and V-ATPase were found between metastatic and non-metastatic groups in the same carcinomas (P < 0.0001). There was also a clear correlation between the expression of ABCG2 and V-ATPase (P ≤ 0.001) in the various groups of pathological grades and TNM stages.ConclusionsBoth ABCG2 and V-ATPase were over-expressed in esophageal squamous cancer cells. Their expression was associated with pathological grade, TNM stage and tumor metastasis in esophageal squamous cancer cells, suggesting interaction relationship between them. ABCG2 and V-ATPase expression may be strongly associated with drug resistance and tumor metastasis.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/3823783918433897

show abstract

Changes of microRNAs-192, 196a and 203 correlate with Barrett's esophagus diagnosis and its progression compared to normal healthy individuals

Cited by 41 publications

References 35 publications

microRNA-192 suppresses the expression of the farnesoid X receptor

microRNA-192 suppresses the expression of the farnesoid X receptor

NF‐κB inhibition reverses acidic bile‐induced miR‐21, miR‐155, miR‐192, miR‐34a, miR‐375 and miR‐451a deregulations in human hypopharyngeal cells

ABCG2/V-ATPase was associated with the drug resistance and tumor metastasis of esophageal squamous cancer cells

Contact Info

Product

Resources

About