MicroRNA-130b regulates the tumour suppressor RUNX3 in gastric cancer

Lai, Kin Wai; Koh, King Xin; Loh, Marie; Tada, Kotaro; Subramaniam, Manish Mani; Lim, Xn Yii; Vaithilingam, Aparna; Salto-Tellez, Manuel; Iacopetta, Barry; Ito, Yoshiaki; Soong, Richie

doi:10.1016/j.ejca.2010.01.036

Cited by 148 publications

(111 citation statements)

References 28 publications

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“…In addition, overexpression of miR-130b could downregulate RUNX3 protein expression, and miR-130b expression was inversely associated with RUNX3 hypermethylation in gastric cancer. This suggests that RUNX3 can be regulated by miRNAs, possibly as an alternative mechanism to hypermethylation (Lai et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-148a Can Regulate Runt-Related Transcription Factor 3 Gene Expression via Modulation of DNA Methyltransferase 1 in Gastric Cancer

Zuo

Xia

et al. 2013

Molecules and Cells

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Underexpression of the gene runt-related transcription factor 3 (RUNX3), an important tumor suppressor, is known to contribute to gastric cancer progression. However, the mechanism underlying aberrant RUNX3 expression has not been fully elucidated. We investigated the role of microRNA-148a (miR-148a) and DNA methyltransferases (DNMTs) in RUNX3 promoter methylation and gene expression. RUNX3 mRNA, RUNX3 protein, and methylation levels were assayed in human gastric cancer tissues and matched normal tissues, and AGS and BGC-823 cells by real-time reverse transcription PCR, Western blot, and methylation-specific PCR, respectively. A correlation between RUNX3 mRNA levels and that of miR-148a was also investigated in gastric cancer tissues. We found that RUNX3 mRNA levels were significantly downregulated in gastric cancer tissues compared with their matched normal tissues, and were closely associated with miR-148a expression. After treatment of human gastric cancer AGS and BGC-823 cells with the DNA methylation inhibitor 5-aza-2'-deoxycytidine, a significant increase in RUNX3 mRNA, RUNX3 protein, and the non-methylated form of the RUNX3 promoter were observed relative to untreated cells. Enforced expression of miR-148a, which can modulate DNMT1 and DNMT3B, also increased the expression of RUNX3 in gastric cancer cells. Knockdown of DNMT1 was associated with increased levels of RUNX3 mRNA and RUNX3 protein, while knockdown of DNMT3B did not have any effect on these in BGC-823 cells. Our results show that miR-148a may regulate RUNX3 expression through modulation of DNMT1-dependent DNA methylation in gastric cancer and highlight a miRNA-epigenetics regulation mechanism of gene expression.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-148a Can Regulate Runt-Related Transcription Factor 3 Gene Expression via Modulation of DNA Methyltransferase 1 in Gastric Cancer

Zuo

Xia

et al. 2013

Molecules and Cells

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“…Functional studies of these miRNAs would be helpful for a better understanding of their contribution to the pathophysiology of schizophrenia. The validated downstream target genes for miR-130b include PDGFRA, RUNX3, ITGB1, PPARG, FMR1, and STAT3, and for miR-193a-3p they include ErbB4, S6K2, and MCL1 (33)(34)(35)(36)(37)(38)(39). These genes can be classified into three groups: schizophrenia susceptibility genes (PDGFRA, PPARG, ErbB4), neurodevelopment-related genes (RUNX3, ITGB1, FMR1, STAT3), and neuroprotective genes (S6K2 and MCL1).…”

Section: Discussionmentioning

confidence: 99%

Detection of Circulating miRNA Levels in Schizophrenia

Wei

Yuan²,

Li³

et al. 2015

AJP

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Objective: Diagnosis of schizophrenia is currently dependent on symptom-based criteria and lacks objective indicators. In this study, the authors investigated whether circulating miRNA can serve as a diagnostic biomarker for schizophrenia.Methods: Global plasma miRNAs were profiled in a test cohort of 164 schizophrenia patients and 187 control subjects, using Solexa sequencing, TaqMan Low Density Array, and quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays. The captured miRNAs were then validated by qRT-PCR assays in an independent cohort of 400 schizophrenia patients, 213 control subjects, and 162 patients with nonschizophrenia psychiatric disorders; the 400 schizophrenia patients underwent a 12-month follow up study of regular treatment with an atypical antipsychotic (risperidone and aripiprazole). Results:The global plasma miRNA screening revealed eight miRNAs that were up-regulated in schizophrenia, as revealed by both assay platforms. The qRT-PCR analysis showed the up-regulation of miR-130b and miR-193a-3p in schizophrenia but not in nonschizophrenia disorders. Conclusions:The up-regulation of miR-130b and miR-193a-3p is a state-independent biomarker for schizophrenia, and these two miRNAs could be used to develop a diagnostic tool for schizophrenia.

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“…In this regard, miR-106b and miR-93 impair TGFb-induced apoptosis in gastric cancer cells by inhibiting Bim expression (Petrocca et al, 2008). Overexpression of miR-130b has also been reported to suppress TGFbinduced Bim expression and apoptosis by targeting RUNX3 in gastric cancer cells (Lai et al, 2010). Moreover, several miRNAs, including miR-15b, miR-16, miR-34 and miR-181b, have been shown to target directly the antiapoptotic protein Bcl-2 and positively regulate apoptosis (Xia et al, 2008;Zhu et al, 2010).…”

Section: Dysregulated Mirnas In Gastric Cancermentioning

confidence: 99%

“…The dysregulated miRNAs and their confirmed targets are listed in Supplementary Table 1 (Volinia et al, 2006;Zhang et al, 2007aZhang et al, , 2008Zhang et al, , 2009Zhang et al, , 2010Kim do et al, 2007;Chan et al, 2008;Choy et al, 2008;Petrocca et al, 2008;Ando et al, 2009;Bandres et al, 2009;Du et al, 2009;Guo et al, 2009;Katada et al, 2009;Kim et al, 2009;Liu et al, 2009;Saito et al, 2009;Takagi et al, 2009;Chen et al, 2010;Fassi Fehri et al, 2010;Gao et al, 2010;Hashimoto et al, 2010;Jiang et al, 2010;Lai et al, 2010;Matsushima et al, 2010;Motoyama et al, 2008Motoyama et al, , 2010Shen et al, 2010;Shinozaki et al, 2010;Tsujiura et al, 2010;Tsukamoto et al, 2010;Ueda et al, 2010;Wan et al, 2010;Wu et al, 2010a;Xia et al, 2008;Xiao et al, 2009;Zhu et al, 2010).…”

Section: Dysregulated Mirnas In Gastric Cancermentioning

confidence: 99%