Epigenetic regulation of microRNA-370 by interleukin-6 in malignant human cholangiocytes

Meng, Fanyin; Wehbe–Janek, Hania; Henson, Roger; Smith, Heather M.; Patel, Tushar

doi:10.1038/sj.onc.1210648

Cited by 226 publications

(194 citation statements)

References 32 publications

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“…As miR-148a was found to be remarkably underexpressed in our and other GC subsets (Katada et al, 2009), and there are clues supporting the occurrence of DNA methylation in GC (Ando et al, 2008), a discrepancy in DNA methylation status is unlikely underlies the difference in miR-370 expression. It was found that miR-370 targets MAP3K8, which in turn inactivates p38MAPK for suppression of cholangiocarcinoma cells (Meng et al, 2008). However, we found that miR-370 also targets TGFb-RII as part of the oncogenicity in GC cells.…”

Section: Discussionmentioning

confidence: 54%

“…As very few studies have ever addressed the functional effects of miR-370, we have extended functional characterization to verify its roles in GC progression. Meng et al (2008) have specified miR-370 as a methylation-dependent miRNA acting as a growth suppressor in cholagiocarcinoma cell lines. Interleukin-6 treatment downregulates miR-370 expression, while 5-aza-dC upregulates miR-370 expression.…”

Section: Discussionmentioning

confidence: 99%

“…The expression of miR-370, miR-222, miR-200c, miR-181c, miR-27a and miR-148a were further analyzed in a total of 33 GC and NCM pairs from the group 1 patients (Table 1) to confirm the changes in expression level in the tumor tissue (Meng et al, 2006(Meng et al, , 2008Liu et al, 2007;Ladeiro et al, 2008;Lujambio et al, 2008). miR-370 was found to be generally overexpressed in GC, with a mean DDCt of 1.45 (Figure 2a).…”

Section: Mir-370 Overexpression In Gcmentioning

confidence: 99%

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Overexpression of miR-370 and downregulation of its novel target TGFβ-RII contribute to the progression of gastric carcinoma

et al. 2011

Oncogene

101

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MicroRNAs (miRNAs) are endogenous non-coding RNAs that are known to be involved in the pathogenesis of tumors. Gastric carcinoma (GC) is a common malignancy worldwide. The aim of this study was the identification of the expression signature and functional roles of aberrant miRNAs in GC. Initial screening established a profile of aberrantly expressed miRNAs in tumors. miR-370 was confirmed to be overexpressed in GC tissues. Higher expression of miR-370 in GC tissues was associated with more advanced nodal metastasis and a higher clinical stage compared with controls. In addition, significantly higher level of miR-370 was noted in the plasma of GC patients compared with controls. Patients having more invasive or advanced tumors also exhibited a higher plasma level of miR-370. In vitro assays indicated that exogenous miR-370 expression enhanced the oncogenic potential of GC cells. The AGS-GFPM2 cells with exogenous miR-370 expression also exhibited enhanced abdominal metastatic dissemination in nude mice. Reporter assays confirmed that miR-370 targeted predicted sites in 3 0 UTR of transforming growth factor-b receptor II (TGFb-RII) gene. The exogenous miR-370 expression decreased TGFb-RII expression and the phosphorylation of Smad3 elicited by TGFb1. The TGFb1-mediated repression in cell migration was reverted by exogenous miR-370 expression. A reverse correlation between miR-370 and TGFb-RII expression was noted in GC tissues. This study concludes that miR-370 is a miRNA that is associated with GC progression by downregulating TGFb-RII. The miRNA expression profile described in this study should contribute to future studies on the role of miRNAs in GC.

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Section: Discussionmentioning

confidence: 54%

Section: Discussionmentioning

confidence: 99%

Section: Mir-370 Overexpression In Gcmentioning

confidence: 99%

See 1 more Smart Citation

Overexpression of miR-370 and downregulation of its novel target TGFβ-RII contribute to the progression of gastric carcinoma

et al. 2011

Oncogene

101

100

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“…Autocrine IL-6 production in cholangiocarcinoma cells also produced resistance to the inhibitory effects of AZA on cell proliferation and soft agar colony formation (Wehbe et al, 2006) associated with altered promoter methylation of several genes. Furthermore, IL-6 epigenetically regulates a number of microRNAs to influence oncogenicity of cholangiocarcinoma cells (Meng et al, 2007). The receptors for both IL-6 and hGH belong to the cytokine receptor superfamily (Waters et al, 1999) and utilize similar signal transduction mechanisms including the JAK pathway (Zhu et al, 2002) demonstrated herein to regulate DNMT expression.…”

Section: Discussionmentioning

confidence: 86%

DNMT3A and DNMT3B mediate autocrine hGH repression of plakoglobin gene transcription and consequent phenotypic conversion of mammary carcinoma cells

et al. 2007

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Directed by microarray analyses, we report that autocrine human growth hormone (hGH) increased the mRNA and protein expression of DNA methyltransferase 1 (DNMT1), DNMT3A and DNMT3B in mammary carcinoma cells. Autocrine hGH stimulation of DNMT3A and DNMT3B expression was mediated by JAK2 and Src kinases, and treatment of mammary carcinoma cells with the DNMT inhibitor, 5 0 -aza-2 0 -deoxycytidine (AZA), abrogated autocrine hGH-stimulated cellular proliferation, apoptosis and anchorage-independent growth. AZA reversed the epitheliomesenchymal transition of mammary carcinoma cells induced by autocrine hGH, to an epithelioid morphology and abrogated cell migration stimulated by autocrine hGH. Autocrine hGH-stimulated hypermethylation of the first exon of the PLAKOGLOBIN gene and AZA abrogated the ability of autocrine hGH to repress plakoglobin gene transcription. Small interfering RNA (siRNA)-mediated depletion of the individual DNMT molecules did not release autocrine hGH repression of PLAKOGLOBIN promoter activity nor did individual DNMT depletion affect autocrine hGH-stimulated migration. However, concomitant siRNA-mediated depletion of both DNMT3A and DNMT3B abrogated hypermethylation of the PLAKO-GLOBIN gene stimulated by autocrine hGH and subsequent repression of plakoglobin gene transcription and increased cell migration. Thus, the autocrine hGHstimulated increases in DNMT3A and DNMT3B expression mediate repression of plakoglobin gene transcription by direct hypermethylation of its promoter and consequent phenotypic conversion of mammary carcinoma cells. Autocrine hGH, therefore, utilizes DNA methylation as a mechanism to exert its oncogenic effects in mammary carcinoma cells.

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“…Recent studies have shown that several miRNAs, such as miR-146a, miR-155, and miR-21, are involved in H. pylori-induced infection (23)(24)(25). MiR-370 has been verified as a tumor suppressor in bladder cancer and cholangiocarcinoma cell lines (26,27). Furthermore, FoxM1 is predicted as a putative target of miR-370 by bioinformatics.…”

Section: Introductionmentioning

confidence: 99%

FoxM1 is Overexpressed in Helicobacter pylori–Induced Gastric Carcinogenesis and Is Negatively Regulated by miR-370

Feng

Wang

Zeng

et al. 2013

Molecular Cancer Research

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Helicobacter pylori (H. pylori) infections are strongly implicated in human gastric mucosa-associated diseases. Forkhead box M1 (FoxM1), a key positive regulator of cell proliferation, is overexpressed in gastric cancer. MicroRNAs are important post-transcriptional regulators of gene expression. In this study, the effects of H. pylori infection on FoxM1 expression and possible mechanisms of carcinogenesis were explored. The expression of FoxM1 was gradually increased in human gastric specimens from inflammation to cancer. FoxM1 upregulation was time-and concentration-dependent in gastric epithelial-derived cell lines infected with H. pylori. CagA, a key virulence factor of H. pylori, was associated with increased FoxM1 expression.

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Epigenetic regulation of microRNA-370 by interleukin-6 in malignant human cholangiocytes

Cited by 226 publications

References 32 publications

Overexpression of miR-370 and downregulation of its novel target TGFβ-RII contribute to the progression of gastric carcinoma

Overexpression of miR-370 and downregulation of its novel target TGFβ-RII contribute to the progression of gastric carcinoma

DNMT3A and DNMT3B mediate autocrine hGH repression of plakoglobin gene transcription and consequent phenotypic conversion of mammary carcinoma cells

FoxM1 is Overexpressed in Helicobacter pylori–Induced Gastric Carcinogenesis and Is Negatively Regulated by miR-370

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