DNA Methylation-Mediated Repression of miR-886-3p Predicts Poor Outcome of Human Small Cell Lung Cancer

Cao, Jianzhong; Song, Yongmei; Bi, Nan; Shen, Jie; Liu, Wenyang; Fan, Jing; Sun, Guogui; Tong, Tong; He, Jié; Shi, Yuankai; Zhang, Xun; Lü, Ning; He, Yinghua; Zhang, Hongyu; Ma, Kelong; Luo, Xiaoying; Deng, Hui; Cheng, Jing; Zhu, Jingde; Wang, Lühua; Zhan, Qimin

doi:10.1158/0008-5472.can-12-3055

Cited by 119 publications

(151 citation statements)

References 48 publications

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“…They discovered that lower miR-150 and miR-886-3p expression levels were associated with a poor OS and PFS. These findings retained statistical significance as independent predictors of survival after adjusting for age, gender and smoking status and confirmed the results of a previous study on the prognostic role of miR-886-3p levels in SCLC (Cao et al 2013). In that study, miR.886-3p expression was found to be regulated by DNA promoter methylation and to potentially repress cell proliferation, migration and invasion.…”

Section: Mirnas As Prognostic Markers In Neuroendocrine Tumorssupporting

confidence: 89%

Circulating tumor cells and miRNAs as prognostic markers in neuroendocrine neoplasms

Zatelli¹,

Grossrubatscher²,

Guadagno³

et al. 2017

Endocrine-Related Cancer

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The prognosis of neuroendocrine neoplasms (NENs) is widely variable and has been shown to associate with several tissue-and blood-based biomarkers in different settings. The identification of prognostic factors predicting NEN outcome is of paramount importance to select the best clinical management for these patients. Prognostic markers have been intensively investigated, also taking advantage of the most modern techniques, in the perspective of personalized medicine and appropriate resource utilization. This review summarizes the available data on the possible role of circulating tumor cells and microRNAs as prognostic markers in NENs.

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Section: Mirnas As Prognostic Markers In Neuroendocrine Tumorssupporting

confidence: 89%

Circulating tumor cells and miRNAs as prognostic markers in neuroendocrine neoplasms

Zatelli¹,

Grossrubatscher²,

Guadagno³

et al. 2017

Endocrine-Related Cancer

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“…Effectively, in human cancer cell lines, DNA methylation has been shown to modulate the miR-886-3p expression [41]. Moreover, miR-886-3p and the pre-miR-886 can strongly repress cell proliferation [23,41]. We found that pre-miR-886 was also responsible for the regulation of cell proliferation in CD4 + T-cells.…”

Section: Discussionmentioning

confidence: 70%

“…We showed also that the DNA methylation of this region could control the VTRNA2-1 expression level in CD4 + T-cells. Effectively, in human cancer cell lines, DNA methylation has been shown to modulate the miR-886-3p expression [41]. Moreover, miR-886-3p and the pre-miR-886 can strongly repress cell proliferation [23,41].…”

Section: Discussionmentioning

confidence: 99%

Aberrantly methylated DNA regions lead to low activation of CD4+ T-cells in IgA nephropathy

et al. 2016

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IgAN (IgA nephropathy) is the most common form of primary glomerulonephritis worldwide and has a strong genetic component. In this setting, DNA methylation could also be an important factor influencing this disease. We performed a genome-wide screening for DNA methylation in CD4(+) T-cells from IgAN patients and found three regions aberrantly methylated influencing genes involved in the response and proliferation of CD4(+) T-cells. Two hypomethylated regions codified genes involved in TCR (T-cell receptor) signalling, TRIM27 (tripartite motif-containing 27) and DUSP3 (dual-specificity phosphatase 3), and an hypermethylated region included the VTRNA2-1 (vault RNA 2-1) non-coding RNA, also known as miR-886 precursor. We showed that the aberrant methylation influences the expression of these genes in IgAN patients. Moreover, we demonstrated that the hypermethylation of the miR-886 precursor led to a decreased CD4(+) T-cell proliferation following TCR stimulation and to the overexpression of TGFβ (transforming growth factor β). Finally, we found a Th1/Th2 imbalance in IgAN patients. The IL (interleukin)-2/IL-5 ratio was notably higher in IgAN patients and clearly indicated a Th1 shift. In conclusion, we identified for the first time some specific DNA regions abnormally methylated in IgAN patients that led to the reduced TCR signal strength of the CD4(+) T-cells and to their anomalous response and activation that could explain the T-helper cell imbalance. The present study reveals new molecular mechanisms underlying the abnormal CD4(+) T-cell response in IgAN patients.

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“…MicroRNAs have been reported as targets of epigenetic events during carcinogenesis. In lung cancer, several miRNAs, such as miR-9-3, miR34b, miR-124-1, miR-124-2, miR-124-3, mir-126, miR-137, miR-152, miR-193a, miR-503, and miR-886-3p, are silenced by DNA hypermethylation [33][34][35][36][37][38][39][40][41]. Furthermore, histone modification may be another possible epigenetic mechanism underlying aberrant miRNA expression.…”

Section: Introductionmentioning

confidence: 99%

Epigenetic silencing of microRNA-373 to epithelial-mesenchymal transition in non-small cell lung cancer through IRAK2 and LAMP1 axes

Seol¹,

Akiyama²,

Shimada³

et al. 2014

Cancer Letters

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The role of microRNAs (miRNAs) in carcinogenesis as tumor suppressors or oncogenes has been widely reported. Epigenetic change is one of the mechanisms of transcriptional silencing of miRNAs in cancer. To identify lung cancer-related miRNAs that are mediated by histone modification, we conducted microarray analysis in the Calu-6 non-small cell lung cancer (NSCLC) cell line after treatment with suberoylanilide hydroxamic acid (SAHA), a histone deacetylase (HDAC) inhibitor. The expression level of miR-373 was enhanced by SAHA treatment in this cell line by microarray and the following quantitative RT-PCR analyses. Treatment with another HDAC inhibitor, Trichostatin A, restored the levels of miR-373 expression in A549 and Calu-6 cells, while demethylation drug treatment did not. Importantly, miR-373 was found to be down-regulated in NSCLC tissues and cell lines. Transfection of miR-373 into A549 and Calu-6 cells attenuated cell proliferation, migration, and invasion and reduced the expression of mesenchymal markers. Additional microarray analysis of miR-373-transfected cells and computational predictions identified IRAK2 and LAMP1 as targets of miR-373. Knockdown of these two genes showed similar biological effects to those of miR-373 overexpression. In clinical samples, overexpression of IRAK2 correlated with decreased disease-free survival of patients with non-adenocarcinoma. In conclusion, we found that miR-373 is silenced by histone modification in lung cancer cells and identified its function as a tumor suppressor and negative regulator of the mesenchymal phenotype through downstream IRAK2 and LAMP1 target genes.

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DNA Methylation-Mediated Repression of miR-886-3p Predicts Poor Outcome of Human Small Cell Lung Cancer

Cited by 119 publications

References 48 publications

Circulating tumor cells and miRNAs as prognostic markers in neuroendocrine neoplasms

Circulating tumor cells and miRNAs as prognostic markers in neuroendocrine neoplasms

Aberrantly methylated DNA regions lead to low activation of CD4+ T-cells in IgA nephropathy

Epigenetic silencing of microRNA-373 to epithelial-mesenchymal transition in non-small cell lung cancer through IRAK2 and LAMP1 axes

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