Vitamin C supplementation reduces expression of circulating miR-451a in poorly controlled type 2 diabetes mellitus
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE154647 | GEO | 2020/07/18
REPOSITORIES: GEO
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Project description:Vitamin C supplementation reduces expression of circulating miR-451a in poorly controlled type 2 diabetes mellitus
| PRJNA646950 | ENA
Project description:MicroRNAs (miRNAs) are small noncoding RNAs that critically regulate gene expression. Their abundance and function have been linked to processes such as senescence and aging. In aged monkey muscle, miR-451a and miR-144-3p were highly upregulated compared to young animals. This led us to hypothesize that the miRNAs 451a/144-3p may be involved in muscle differentiation. We found that these miRNAs are downregulated during the differentiation of C2C12 myoblasts. Overexpression of miR-451a, but not miR-144-3p, robustly impeded the differentiation, suggesting an inhibitory role for miR-451a. We further investigated the potential regulatory targets of miR-451a and identified Sparc mRNA, encoding a secreted protein acidic and rich in cysteine (SPARC), which is involved in wound healing and cellular differentiation. Interestingly, we found that miR-451a suppresses Sparc mRNA translation according to the analysis of polysome profile. Our findings show that miR-451a is downregulated in differentiated myoblasts and decreases C2C12 differentiation at least in part by the suppression of SPARC biosynthesis.
2019-04-03 | GSE119186 | GEO
Project description:To filter the up-regulated gene induced by miR-451a overexpression and in cetuximab resistant HNSCC cell. We employed whole genome microarray. The HNSCC cell CAL27 was used as a control sample. CAL27_CTX, the cetuximab resistant CAL27 was compared with CAL27. The miR-451a overexpressed CAL27_451a sample was compared with the CAL27_NC sample. CAL27_CTX and CAL27_451A samples were collected after 48h of cetuximab treatment. The microarray results were taken together with ChIRP-seq analysis and bioinformatics analysis for miR-451a binding and enhancer analysis to eventually find the nuclear acticating target of miR-451a
2024-01-01 | GSE245159 | GEO
Project description:BackgroundVitamin C is an essential element required for normal metabolic function. We investigated the effect of vitamin C supplementation on circulating miRNA (miR) expression in subjects with poorly controlled type 2 diabetes mellitus (T2DM). Changes in miR expression were also correlated with clinical measures of disease.MethodsPre- and post-vitamin C supplementation samples from five participants who had increased vitamin C levels, improved oxidative status and polymorphonuclear (PMN) function after receiving 1,000 mg of vitamin C daily for six weeks were screened for miRNA expression using the NanoString miRNA assay. Differences in miRNA expression identified from the miRNA screen were validated by qRT-PCR.ResultsFour miRNAs showed significantly different expression post-vitamin C supplementation relative to baseline, including the down-regulation of miR-451a (-1.72 fold change (FC), p = 0.036) and up-regulation of miR-1253 (0.62 FC, p = 0.027), miR-1290 (0.53 FC, p = 0.036) and miR-644a (0.5 FC, p = 0.042). The validation study showed only miR-451a expression was significantly different from baseline with vitamin C supplementation. MiR-451a expression was negatively correlated with vitamin C levels (r = - 0.497, p = 0.049) but positively correlated with levels of malondialdehyde (MDA) (r = 0.584, p = 0.017), cholesterol (r = 0.564, p = 0.022) and low-density lipoproteins (LDL) (r = 0.522, p = 0.037). Bioinformatics analysis of the putative target genes of miR-451a indicated gene functions related to signaling pathways involved in cellular processes, such as the mammalian target of rapamycin (mTOR) signaling pathway.ConclusionsVitamin C supplementation altered circulating miR-451a expression. The results from this pilot study suggest that miRNAs could be used as biomarkers to indicate oxidative status in subjects with T2DM and with poor glycemic control and could lead to a novel molecular strategy to reduce oxidative stress in T2DM.
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Project description:Distal cholangiocarcinoma (dCCA) is a biliary tract cancer with dismal prognosis and is often preceded by biliary intraepithelial neoplasia (BilIN) as a non-invasive precursor lesion. We found that miR-451a is downregulated in dCCA. Overexpression of mimic-451a in the CCA cell line SNU478 revealed multiple downregulated genes and potential miR-451a candidate targets.
2020-09-01 | GSE147969 | GEO
Project description:Cetuximab resistance has been a major challenge for head and neck squamous cell carcinoma (HNSCC) during target therapy. Yet the mechanism that caused cetuximab resistance, especially the miRNA regulation therein remains unclear. With growing evidence suggests that miRNAs may function within the cell nucleus and act as “nuclear activating miRNAs” for targeting the promoter region or enhancers related to target genes. They are believed to regulate diseases development including tumorigenesis. This study elucidates a novel mechanism underlying cetuximab resistance in HNSCC involving the nuclear activation of KDM7A transcription via miR-451a. Herein, small RNA sequencing, qRT-PCR and FISH results provide compelling evidence of miR-451a nuclear enrichment with cetuximab treatment. ChIRP-seq, microarray, bioinformatic analysis and dual luciferase reporter assay results show that miR-451a interacts with an enhancer region in KDM7A, activating its expression and further facilitating cetuximab resistance. It is also demonstrated that activation of KDM7A by nuclear miR-451a is induced by cetuximab treatment and is AGO2 dependent. Analyses of HNSCC samples through logistic regression indicated the significance of miR-451a and KDM7A in cetuximab resistance. These discoveries hold promise for the potential utilization of miR-451a and KDM7A as valuable biomarkers for cetuximab resistance and emphasize the function of nuclear activating miRNAs.
2024-01-01 | GSE244948 | GEO
Project description:Cetuximab resistance has been a major challenge for head and neck squamous cell carcinoma (HNSCC) during target therapy. Yet the mechanism that caused cetuximab resistance, especially the miRNA regulation therein remains unclear. With growing evidence suggests that miRNAs may function within the cell nucleus and act as “nuclear activating miRNAs” for targeting the promoter region or enhancers related to target genes. They are believed to regulate diseases development including tumorigenesis. This study elucidates a novel mechanism underlying cetuximab resistance in HNSCC involving the nuclear activation of KDM7A transcription via miR-451a. Herein, small RNA sequencing, qRT-PCR and FISH results provide compelling evidence of miR-451a nuclear enrichment with cetuximab treatment. ChIRP-seq, microarray, bioinformatic analysis and dual luciferase reporter assay results show that miR-451a interacts with an enhancer region in KDM7A, activating its expression and further facilitating cetuximab resistance. It is also demonstrated that activation of KDM7A by nuclear miR-451a is induced by cetuximab treatment and is AGO2 dependent. Analyses of HNSCC samples through logistic regression indicated the significance of miR-451a and KDM7A in cetuximab resistance. These discoveries hold promise for the potential utilization of miR-451a and KDM7A as valuable biomarkers for cetuximab resistance and emphasize the function of nuclear activating miRNAs.
2024-01-01 | GSE245153 | GEO
Project description:Many patients with Oesophageal Adenocarcinoma (OAC) that undergo chemoradiotherapy do not benefit from treatment due to therapy resistance. We therefore investigated the association of microRNAs, which regulate gene expression, with the response to individual treatments, focusing on radiation, to both better understand the mechanisms involved in resistance and to find potential biomarkers. Intrinsic radiation resistance and chemotherapy drug resistance were assessed in 8 OAC cell lines, and miRNA expression profiling was performed via high throughput qPCR. miRNAs were discovered that were either uniquely associated with resistance to radiation, cisplatin, or 5-FU, or were common to 2 or all 3 of the treatments. Target mRNA pathway analyses indicated several potential mechanisms of treatment resistance. miRNAs associated with the in-vitro treatment responses were then investigated for association with pathologic response to neoadjuvant chemoradiotherapy (nCRT) in pre-treatment serums of 39 patients with OAC. Hsa-miR-451a was associated uniquely with resistance to radiation treatment in the cell lines, and with the response to nCRT in patient serums. Inhibition of hsa-miR-451a in the radiation resistant OAC cell line OE19 increased radiosensitivity (Survival Fraction 73% vs. 87%, p=0.0003), and altered RNA expression.
2020-12-15 | GSE161148 | GEO
Project description:Colorectal cancer (CRC) ranks third in incidence and second in mortality among cancers worldwide. Emerging researches showed that microRNAs (miRNAs) play an important role in CRC progression. Here, we aimed to investigate the expression and regulatory mechanism of miR-1290 in CRC. miR-1290 is significantly overexpressed in CRC primary tissues and metastatic tissues compared to that in normal tissues, and up-regulated miR-1290 is correlated with poor overall survival (OS) of CRC patients. Functional experiments showed that miR-1290 can promote the proliferation, migration, invasion and inhibit apoptosis of CRC cells. Mechanistically, miR-1290 directly targets KLF9 and promotes the malignancy progression of CRC cells through regulating MMP9 and p53 expression, subsequently. In addition, high H3K4me3 levels in miR-1290 promoter region activate its transcription in CRC. In summary, our study demonstrated the expression and regulatory mechanism of miR-1290 in CRC which supports the notion that therapeutic targeting of miR-1290 may be a promising treatment approach for CRC patients.
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Project description:Of the four primary subgroups of medulloblastoma, the most frequent cytogenetic abnormality, i17q, distinguishes Groups 3 and 4 which carry the highest mortality; haploinsufficiency of 17p13.3 is a marker for particularly poor prognosis. At the terminal end of this locus lies miR-1253, a brain-enriched microRNA that regulates bone morphogenic proteins during cerebellar development. We hypothesized miR-1253 confers novel tumor-suppressive properties in medulloblastoma. Using two different cohorts of medulloblastoma samples, we first studied the expression and methylation profiles of miR-1253. We then explored the anti-tumorigenic properties of miR-1253, in parallel with a biochemical analysis of apoptosis and proliferation, and isolated oncogenic targets using high-throughput screening. Deregulation of miR-1253 expression was noted, both in medulloblastoma clinical samples and cell lines, by epigenetic silencing via hypermethylation; specific de-methylation of miR-1253 not only resulted in rapid recovery of expression but also a sharp decline in tumor cell proliferation and target gene expression. Expression restoration also led to a reduction in tumor cell virulence, concomitant with activation of apoptotic pathways, cell cycle arrest and reduction of markers of proliferation. We identified two oncogenic targets of miR-1253, CDK6 and CD276, whose silencing replicated the negative trophic effects of miR-1253. These data reveal novel tumor-suppressive properties for miR-1253, i.e., (i) loss of expression via epigenetic silencing; (ii) negative trophic effects on tumor aggressiveness; and (iii) downregulation of oncogenic targets.
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