MiRNAs and miRNA Polymorphisms Modify Drug Response

Li, Mu-Peng; Hu, Yaodong; Hu, Xiaolei; Zhang, Yan-Jiao; Yi, Yang; Jiang, Chun; Tang, Jie; Chen, Xiaoping

doi:10.3390/ijerph13111096

Cited by 31 publications

(18 citation statements)

References 143 publications

(201 reference statements)

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“…Nevertheless, there are con icting results for the association between the presence of miR-608 rs4919510 and susceptibility to tumors. [8,[26][27][28]. Although IPF and lung cancer are sometimes seen in the same patients [29], since we observed an upregulation in the miR-608, rs4919510 was not studied and our focus was shifted to other directions.…”

Section: Cdc42 Levels Are Signi Cantly Reduced In Ipf Patient Samplesmentioning

confidence: 83%

Mir-608 Overexpression in Idiopathic Pulmonary Fibrosis (IPF) is Related to Acetylcholinesterase Single Nucleotide Polymorphism (SNP)

Shochet

Israeli‐Shani

Kains

et al. 2020

Preprint

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Background: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease that causes scarring of the lungs. The disease is associated with the Usual Interstitial Pneumonia (UIP) pattern, which was not yet fully recapitulated by an animal model. Therefore, the disease is considered ‘human specific’. miRNA-608 is a primate specific miRNA with many potential targets, such CdC42 and Interlukin-6 (IL-6) that were previously implicated in IPF pathology. Objective: To test miR-608 expression and its targets in IPF patient samples.Methods: RNA was extracted from Formalin fixed paraffin embedded (FFPE) tissue sections (N=18). miRNA-608 expression and Cdc42 and IL-6 levels were analyzed by qPCR. Acetylcholinesterase (AChE) is another target of miRNA-608. Its' rs17228616 allele has a single-nucleotide polymorphism (SNP) causing weakened miR-608 interaction (C2098A). Thus, DNA was extracted from whole blood samples from 56 subjects with fibrosing interstitial lung disease (ILD) and this region was sequenced for assessment of rs17228616 allele polymorphism.Results: MiR-608 is significantly overexpressed in IPF samples, in comparison with controls (p<0.05). Cdc42 and IL-6 levels were lower in the IPF patient samples compared with control samples (p<0.001 and p<0.05, respectively). The frequency of the rs17228616 minor A-allele was 17/56 (30.4%) with all patients being heterozygous. This result is significant vs. the published Israeli cohort of healthy individuals, which reported 17% prevalence of this allele in healthy control volunteers (p=0.01, OR = 2.1, CI 95% [1.19-3.9]).Conclusion: MiR-608 is overexpressed in IPF patients. While the exact mechanism remains to be discovered, it could potentially promote fibrotic disease.

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Section: Cdc42 Levels Are Signi Cantly Reduced In Ipf Patient Samplesmentioning

confidence: 83%

Mir-608 Overexpression in Idiopathic Pulmonary Fibrosis (IPF) is Related to Acetylcholinesterase Single Nucleotide Polymorphism (SNP)

Shochet

Israeli‐Shani

Kains

et al. 2020

Preprint

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“…Bu genlerdeki polimorfizmler miRNA polimorfizmleri veya miRSNP'ler olarak adlandırılmaktadır ve çok yaygındır. MiRSNP'ler, pri-, pre-ve olgun miRNA dizileri ve miRNA biyogenezinde görevli genler ve beraberinde fonksiyonel genlerin miRNA bağlanma bölgelerinde mevcut olan polimorfizmlerini kapsamaktadır (70,71). Bu genetik varyasyonların ilacın farmakokinetik özelliklerini nasıl etkilediğini anlamak için çok sayıda çalışma yapılmıştır.…”

Section: Mirna'ların Kanserdeki Rolüunclassified

Kanserde MikroRNA’lar ve İlaç Yanıtı

Acar

Yeşilot

2018

SDÜ Tıp Fakültesi Dergisi

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MikroRNA'lar (miRNA), hedef gen ekspresyonunu post-transkripsiyonel olarak kontrol eden küçük kodlanmayan RNA molekülleridir. miRNA'ların hedef genleri baskılayarak büyüme, gelişme, farklılaşma ve hücre ölümü süreçlerinin düzenlenmesinde önemli rol oynadığına dair çok sayıda çalışma mevcuttur. MiRNA'ların düzenlenmesindeki bozuklukların kanser ile bağlantılı olması bu bağlamda şaşırtıcı değildir. Buna ek olarak, miRNA ifadelerinin ilaçlar tarafından değiştirilebildiği ve miRNA'ların kanser tedavisinde ilaç metabolizmasının düzenlenmesini ve toksisiteyi etkilediği bildirilmiştir. İlaç yanıtı, hem genetik hem de çevresel faktörler tarafından düzenlenen karmaşık bir süreçtir. Bugüne kadar farklı miRNA'ların birçok antikanser terapiye karşı duyarlılığı öngördüğü veya etkilediği bulunmuştur. Bu derleme de, miRNA biyogenezini takiben, miRNA'ların kanser, ilaç yanıtı ve antikanser tedavileri üzerindeki potansiyel rolünü ortaya koyan mevcut çalışmaların tartışılması amaçlanmıştır.

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“…Similarly, miRNAs affect drug response directly or indirectly by regulating the expression of genes involved in drug transportation, metabolism, and downstream signaling pathways. Furthermore, single nucleotide polymorphisms in miRNA‐encoding genes may be responsible for interindividual differences in drug response …”

Section: Micrornasmentioning

confidence: 99%

“…M ICRORNAS ARE SMALL, non-coding, singlestranded, evolutionarily conserved RNA molecules of [18][19][20][21][22][23][24][25] nucleotides that regulate the expression of target genes. MicroRNAs have come a long way, from the first miRNA (lin-4) discovered in Caenorhabditis elegans.…”

Section: Micrornasmentioning

confidence: 99%

See 1 more Smart Citation

Sorafenib response in hepatocellular carcinoma: MicroRNAs as tuning forks

Kanthaje

Makol

Chakraborti

2017

Hepatology Research

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Hepatocellular carcinoma (HCC) is the primary liver malignancy that contributes towards the second most common cause of cancer‐related mortality. The targeted chemotherapeutic agent, sorafenib, is known to show a statistically significant but limited overall survival advantage in advanced HCC. However, the individual patient response towards sorafenib varies drastically, with most experiencing stable disease and few with partial response; complete response is very rare. Progressive disease despite the treatment is also evident in many patients, indicating drug resistance. These varied responses have been linked with the modulation of several intracellular signaling pathways. Notably, the regulation of these pathways through diverse operating biomolecules, including microRNAs (miRNAs), is the focus of recent studies. MicroRNAs are tiny, non‐coding RNA molecules that regulate the expression of several target genes. In addition, miRNAs are known to play a role in the progression of HCC carcinogenesis. Interestingly, miRNAs have also been identified to play differential roles in terms of sorafenib response in HCC such as biomarkers and functional modulation of cellular response to sorafenib, hence, they are also being therapeutically evaluated. This review outlines the role of reported miRNAs in different aspects of sorafenib response in HCC.

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MiRNAs and miRNA Polymorphisms Modify Drug Response

Cited by 31 publications

References 143 publications

Mir-608 Overexpression in Idiopathic Pulmonary Fibrosis (IPF) is Related to Acetylcholinesterase Single Nucleotide Polymorphism (SNP)

Mir-608 Overexpression in Idiopathic Pulmonary Fibrosis (IPF) is Related to Acetylcholinesterase Single Nucleotide Polymorphism (SNP)

Kanserde MikroRNA’lar ve İlaç Yanıtı

Sorafenib response in hepatocellular carcinoma: MicroRNAs as tuning forks

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