Role of miR-19a targeting TNF-α in mediating ulcerative colitis

Chen, Bin; She, Shifeng; Li, Detang; Liu, Zhihui; Yang, Xiaojun; Zeng, Zhirong; Liu, Fengbin

doi:10.3109/00365521.2013.800991

Cited by 33 publications

(16 citation statements)

References 63 publications

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“…Gantier et al (31) reported that miR-19a was able to inhibit A20/Tnfaip3, Rnf11, Fbxl11/Kdm2a, and Zbtb16, and promote the transduction of nuclear factor-κB, and that the downregulation of Rnf11 expression could decrease the expression levels of IL-6 and IL-8. In colitis tissue samples, miR-19a expression was downregulated, and the expression levels of TNF-α were increased (32). However, in the colitis mouse model, a luciferase vector demonstrated that TNF-α is the target gene of miR-19a (33).…”

Section: Discussionmentioning

confidence: 99%

Effect of miR-19a and miR-21 on the JAK/STAT signaling pathway in the peripheral blood mononuclear cells of patients with systemic juvenile idiopathic arthritis

Xie

et al. 2016

Experimental and Therapeutic Medicine

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Abstract.Overexpression of the components of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway are key factors of the pathogenic mechanisms underlying systematic juvenile idiopathic arthritis (SJIA). The present study aimed to investigate the association between microRNA (miR)-19a, miR-21 and the JAK/STAT signaling pathway. A total of 20 patients with SJIA were included in the study, and peripheral blood mononuclear cells (PBMCs) from 20 normal controls were also collected. RNAiso was used to extract total RNA, and the RNA was then reverse transcribed into cDNA. Primers were designed to detect the mRNA of miR-19a and miR-21, and U6 was set as the internal parameter. In addition, the mRNA of STAT3, suppressor of cytokine signaling 3 (SOCS3), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) was detected, and β-actin was set as the internal parameter. Reverse transcription-quantitative polymerase chain reaction was performed to detect the expression levels of these proteins in patients with SJIA and control subjects, and non-parametric tests were used to analyze the statistical differences in 2 -ΔΔCq between the two groups. The expression levels of miR-19a and miR-21 were significantly lower in the SJIA group compared with the control group (P<0.05). SOCS3, TNF-α and STAT3 were shown to be the target genes of miR-19a and miR-21, as determined by Targetscan. The expression levels of STAT3, SOCS3, TNF-α and IL-6 mRNA were significantly higher compared with those of the control group (P<0.05). In the PBMCs of sthe patients with SJIA, miR-19a and miR-21 expression levels were lower compared with those of the control group, and the JAK/STAT signaling pathway was activated, which indicated that miR-19a and miR-21 may participate in the activation of the JAK/STAT signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Effect of miR-19a and miR-21 on the JAK/STAT signaling pathway in the peripheral blood mononuclear cells of patients with systemic juvenile idiopathic arthritis

Xie

et al. 2016

Experimental and Therapeutic Medicine

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“…This suggested that miR-19a was essential for TNF-α-mediated EMT and provided mechanistic insight into the role of miR-19a in mediating some of the TNF-α mediated EMT activity. Considering, TNF-α has been reported previously to be a miR-19a gene target in ESCC34 and ulcerative colitis35, we had conducted the western blot assay to determine whether TNF-α would be a target in CRC cells. Ectopic miR-19a expression decreased the expression of TNF-α in both HCT 116 and Caco-2 cells (Supplementary Fig.…”

Section: Discussionmentioning

confidence: 99%

Hsa-miR-19a is associated with lymph metastasis and mediates the TNF-α induced epithelial-to-mesenchymal transition in colorectal cancer

Huang

Wang

Wen

et al. 2015

Sci Rep

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Lymph node metastasis is an important factor determining the outcome of colorectal cancer. Although epithelial-to-mesenchymal transition (EMT), TNF-α and microRNA (miRNA) have been found to play important roles in lymph node metastasis, the underlying molecular mechanism remains unclear. Here we reported that high expression of microRNA-19a (miR-19a) was associated with lymph node metastasis and played an important role in TNF-α-induced EMT in colorectal cancer (CRC) cells. We analyzed miR-19a expression in surgical tissue specimens from 11 CRC patients and 275 formalin-fixed, paraffin-embedded CRC patients. We found that miR-19a was up-regulated in CRC tissues and high expression of miR-19a was significantly associated with lymph node metastasis. We further analyzed miR-19a lymph node metastasis signature in an external validation cohort of 311 CRC cases of the TCGA. MiR-19a was found to be significantly associated with lymph node metastasis in rectal cancer. In vitro, we showed that overexpression of miR-19a in human CRC cell lines promoted cell invasion and EMT. Furthermore, miR-19a was up-regulated by TNF-α and miR-19a was required for TNF-α-induced EMT and metastasis in CRC cells. Collectively, miR-19a played an important role in mediating EMT and metastatic behavior in CRC. It may serve as a potential marker of lymph node metastasis.

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“…Although miR-19a and miR-19b were found to be the most significant miRNAs of the miR-17-92 cluster, and were reported to have a broad and significant roles in normal or abnormal cells of human body, 18, 19, 20, 21 the exact function and the potential mechanisms of them in gastric cancer has not been fully clarified. We have previously found that the expression of the miR-17-92 cluster members were gradually changed during the differentiation of gastric cancer stem cells, among the six members, miR-19b/20a/92a can regulate the self-renewal of gastric cancer stem cells through activating the Wnt- β -catenin signalling.…”

Section: Discussionmentioning

confidence: 99%

MiR-19a/b modulate the metastasis of gastric cancer cells by targeting the tumour suppressor MXD1

Yang

et al. 2014

Cell Death Dis

105

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The microRNAs 19a and 19b, hereafter collectively referred to as miR-19a/b, were recognised to be the most important miRNAs in the oncomiRs—miR-17-92 cluster. However, the exact roles of miR-19a/b in cancers have not been elucidated. In the present study, miR-19a/b was found to be over-expressed in gastric cancer tissues and significantly associated with the patients' metastasis of gastric cancer. Using gain or loss-of-function in in vitro and in vivo experiments, a pro-metastatic function of miR-19a/b was observed in gastric cancer. Furthermore, reporter gene assay and western blot showed that MXD1 is a direct target of miR-19a/b. Functional assays showed that not only MXD1 had an opposite effect to miR-19a/b in the regulation of gastric cancer cells, but also overexpression of MXD1 reduced both miR-19a/b and c-Myc levels, indicating a potential positive feedback loop among miR-19a/b, MXD1 and c-Myc. In conclusion, miR-17-92 cluster members miR-19a/b facilitated gastric cancer cell migration, invasion and metastasis through targeting the antagonist of c-Myc -- MXD1, implicating a novel mechanism for the malignant phenotypes of gastric cancer.

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Role of miR-19a targeting TNF-α in mediating ulcerative colitis

Abstract: Taken together, this study determines the levels of miR-19a and TNF-α in both DSS-induced experimental murine colitis and human UC and further demonstrates that miR-19a might directly regulate TNF-α. The findings may provide a new insight in the clinical treatment of UC.

Cited by 33 publications

References 63 publications

Effect of miR-19a and miR-21 on the JAK/STAT signaling pathway in the peripheral blood mononuclear cells of patients with systemic juvenile idiopathic arthritis

Effect of miR-19a and miR-21 on the JAK/STAT signaling pathway in the peripheral blood mononuclear cells of patients with systemic juvenile idiopathic arthritis

Hsa-miR-19a is associated with lymph metastasis and mediates the TNF-α induced epithelial-to-mesenchymal transition in colorectal cancer

MiR-19a/b modulate the metastasis of gastric cancer cells by targeting the tumour suppressor MXD1

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