rs11671784 G/A variation in miR-27a decreases chemo-sensitivity of bladder cancer by decreasing miR-27a and increasing the target RUNX-1 expression

Deng, Ying; Bai, Hansong; Hu, Honglin

doi:10.1016/j.bbrc.2015.01.109

Cited by 39 publications

(35 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, great caution should be used in interpreting the findings from the three preclinical studies investigating the effect of rs11671784 on miR-27a expression. 20,22,23 The allele frequency of rs11671784 in this study, in the previous study by Amstutz et al and according to the 1000 genomes project, is around 0.010-0.020 in European and American populations, and was reported to be 0.000 in Chinese populations. 21,26 Remarkably, the allele frequencies reported in the three preclinical investigations, all performed in China, were much higher, between 0.30 and 0.50.…”

Section: Discussionsupporting

confidence: 63%

“…Three preclinical investigations have shown that the rs11671784 T allele is associated with reduced miR-27a expression, as opposed to the increase in expression caused by rs895819. 20,22,23 This appears to contradict an increased risk of toxicity in carriers of this variant, as a reduction in miR27a expression is expected to lead to higher DPD activity. However, great caution should be used in interpreting the findings from the three preclinical studies investigating the effect of rs11671784 on miR-27a expression.…”

Section: Discussionmentioning

confidence: 99%

“…19,22 Associations between MIR27A variants and risk of severe toxicity were first investigated in the overall population, by including both MIR27A variants in the logistic model, as well as the DPYD variants (as a dichotomized variable reflecting the presence of zero vs. 1 DPYD variant alleles). A statistical interaction term between MIR27A variants (zero vs. 1 variant alleles) and DPYD variants (zero vs. 1 variant alleles) was then analyzed, in view of the anticipated interaction and stronger effect of MIR27A variants in patients carrying DPYD variants.…”

Section: Endpoints and Data Analysismentioning

confidence: 99%

“…A second polymorphism in MIR27A, rs11671784, has also been associated with miR-27a expression, but its clinical relevance in patients treated with fluoropyrimidines remains unclear. [21][22][23] If the predictive value of MIR27A polymorphisms in combination with DPYD variants can be confirmed, this has important implications for genetic screening strategies to identify patients at risk of fluoropyrimidine-associated toxicity. MIR27A genotyping might be of specific value in combination with DPYD variants that have a more modest effect on DPD activity, such as c.1129-5923C>G and possibly the c.1601G>A variant.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Rs895819 in MIR27A improves the predictive value of DPYD variants to identify patients at risk of severe fluoropyrimidine‐associated toxicity

Meulendijks

Henricks

Amstutz

et al. 2016

Intl Journal of Cancer

View full text Add to dashboard Cite

The objective of this study was to determine whether genotyping of MIR27A polymorphisms rs895819A>G and rs11671784C>T can be used to improve the predictive value of DPYD variants to identify patients at risk of severe fluoropyrimidine-associated toxicity (FP-toxicity). Patients treated previously in a prospective study with fluoropyrimidine-based chemotherapy were genotyped for rs895819 and rs11671784, and DPYD c.2846A>T, c.1679T>G, c.1129-5923C>G and c.1601G>A. The predictive value of MIR27A variants for early-onset grade 3 FP-toxicity, alone or in combination with DPYD variants, was tested in multivariable logistic regression models. Random-effects meta-analysis was performed, including previously published data. A total of 1,592 patients were included. Allele frequencies of rs895819 and rs11671784 were 0.331 and 0.020, respectively. In DPYD wild-type patients, MIR27A variants did not affect risk of FP-toxicity (OR 1.3 for 1 variant MIR27A allele vs. none, 95% CI: 0.87-1.82, p 5 0.228). In contrast, in patients carrying DPYD variants, the presence of 1 rs895819 variant allele was associated with increased risk of FP-toxicity (OR 4.9, 95% CI: 1.24-19.7, p 5 0.023). Rs11671784 was not associated with FP-toxicity (OR 2.9, 95% CI: 0.47218.0, p 5 0.253). Patients carrying a DPYD variant and rs895819 were at increased risk of FP-toxicity compared to patients wild type for rs895819 and DPYD (OR 2.4, 95% CI: 1.27-4.37, p 5 0.007), while patients with a DPYD variant but without a MIR27A variant were not (OR 0.3 95% CI: 0.0621.17, p 5 0.081). In meta-analysis, rs895819 remained significantly associated with FP-toxicity in DPYD variant allele carriers, OR 5.4 (95% CI: 1.83-15.7, p 5 0.002). This study demonstrates the clinical validity of combined MIR27A/DPYD screening to identify patients at risk of severe FP-toxicity.Fluoropyrimidines are among the most frequently prescribed anticancer drugs for gastrointestinal, breast and head and neck cancers. Of the patients treated, 10-30% experiences severe, potentially lethal, fluoropyrimidine-associated toxicity. [1][2][3][4] The most well-established cause of intolerance to fluoropyrimidines is deficiency of the main 5-fluorouracil (5-FU) metabolic enzyme, dihydropyrimidine dehydrogenase (DPD).5-8 DPD deficiency can be the result of polymorphisms in DPYD-the gene encoding DPD-and DPYD variants have therefore received wide-spread attention as predictors of fluoropyrimidine-associated toxicity. 3,[9][10][11][12]

show abstract

Section: Discussionsupporting

confidence: 63%

Section: Discussionmentioning

confidence: 99%

Section: Endpoints and Data Analysismentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Rs895819 in MIR27A improves the predictive value of DPYD variants to identify patients at risk of severe fluoropyrimidine‐associated toxicity

Meulendijks

Henricks

Amstutz

et al. 2016

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…The function of miRNA polymorphisms in cancers has been explored in many studies, including nonsmall-cell lung cancer (NSCLC) [20], papillary thyroid carcinoma [21], hepatocellular carcinoma [22], and bladder cancer [23]. Recently, polymorphisms in miR-27a (rs895819), miR-570 (rs4143815), and miR-181a (rs12537) altering miRNA processing and expression have been extensively studied in various cancers [24][25][26][27][28][29][30][31]. Some of these target genes include V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS), ras-related protein (RAP1B), ribosomal protein S6 kinase (RPS6KA3), mitogen-activated protein kinase kinase 1 (MAP2K1), protein phosphatase 2B regulatory subunit 1 (PPP3R1) [regulated by miR-181a], forkhead box (FOX1), KRAS, MAP2K7, MAP2K4, MAP3K4, [targets genes of miR-27a], KRAS, G1/S-specific cyclin-D3 (CCND3), CCND2, cAMP-response element-binding protein (CREBBP), serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform (PPP3CC), phosphatase and tensin homolog (PTEN) [target genes of miR-570] (http://bioinfo.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of miR-27a, miR-181a, and miR-570 Genetic Variants with Gallbladder Cancer Susceptibility and Treatment Outcome in a North Indian Population

et al. 2015

View full text Add to dashboard Cite

show abstract

Noncoding RNAs in Therapeutic Resistance of Cancer

Jia

Yang

2016

Advances in Experimental Medicine and Biology

View full text Add to dashboard Cite

Despite the encouraging advances made to date in cancer therapy, the benefits to patients are frequently offset by the development of resistance to therapeutics. Given their involvement in regulating multiple aspects of gene expression and cell signaling that dictates the behaviors of malignant cells, it is not surprising that noncoding RNAs (ncRNAs) play pivotal roles in the resistance of cancers to clinically available therapeutics. Aberrant expression of these ncRNAs, attributed to inherent defects or stress-responsive variations, mediates cellular signaling that compensates for unfavorable molecular events elicited by the therapeutics, thereby preventing the pharmaceuticals from exerting their desired effects on their cellular targets; alternatively, ncRNAs may regulate cancer therapeutic sensitivity by affecting drug accessibility to neoplastic cells and in vivo drug metabolism. In addition, dysregulation of ncRNA expression in cancer stromal cells can impair the responsiveness of neoplastic cells to appropriate therapies. In this chapter, we will describe ncRNA-related mechanisms underlying cancer resistance to routine therapeutics, hopefully providing rationales for the development of drug-sensitizing strategies targeted against or based on these ncRNAs.

show abstract

rs11671784 G/A variation in miR-27a decreases chemo-sensitivity of bladder cancer by decreasing miR-27a and increasing the target RUNX-1 expression

Cited by 39 publications

References 15 publications

Rs895819 in MIR27A improves the predictive value of DPYD variants to identify patients at risk of severe fluoropyrimidine‐associated toxicity

Rs895819 in MIR27A improves the predictive value of DPYD variants to identify patients at risk of severe fluoropyrimidine‐associated toxicity

Evaluation of miR-27a, miR-181a, and miR-570 Genetic Variants with Gallbladder Cancer Susceptibility and Treatment Outcome in a North Indian Population

Noncoding RNAs in Therapeutic Resistance of Cancer

Contact Info

Product

Resources

About