The impact of microRNAs and alternative splicing in pharmacogenomics

Passetti, Fábio; Ferreira, Carlos Gil; Costa, Fabrício F.

doi:10.1038/tpj.2008.14

Cited by 54 publications

(47 citation statements)

References 131 publications

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“…The role of miRNAs in control of proliferation, differentiation, and apoptosis; the location of several miRNA genes at sites of translocation breakpoints or deletions; and their aberrant expression in many tumors indicated that they can function as tumor suppressors and oncogenes (13). Furthermore, selected miRNAs may influence response to chemotherapy (14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-21 in Pancreatic Cancer: Correlation with Clinical Outcome and Pharmacologic Aspects Underlying Its Role in the Modulation of Gemcitabine Activity

et al. 2010

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MicroRNA-21 (miR-21) was reported to be overexpressed and contributes to invasion and gemcitabine resistance in pancreatic ductal adenocarcinoma (PDAC). The aim of this study was to evaluate whether miR-21 expression was associated with the overall survival (OS) of PDAC patients treated with gemcitabine and to provide mechanistic insights for new therapeutic targets. miR-21 expression was evaluated in cells (including 7 PDAC cell lines, 7 primary cultures, fibroblasts, and a normal pancreatic ductal cell line) and tissues (neoplastic specimens from 81 PDAC patients and normal ductal samples) isolated by laser microdissection. The role of miR-21 on the pharmacologic effects of gemcitabine was studied with a specific miR-21 precursor (pre-miR-21). Patients with high miR-21 expression had a significantly shorter OS both in the metastatic and in the adjuvant setting. Multivariate analysis confirmed the prognostic significance of miR-21. miR-21 expression in primary cultures correlated with expression in their respective tissues and with gemcitabine resistance. Pre-miR-21 transfection significantly decreased antiproliferative effects and apoptosis induction by gemcitabine, whereas matrix metalloproteinase (MMP)-2/MMP-9 and vascular endothelial growth factor expression were upregulated. Addition of inhibitors of phosphoinositide 3-kinase and mammalian target of rapamycin resulted in decrease of phospho-Akt and prevented pre-miR-21-induced resistance to the proapoptotic effects of gemcitabine. miR-21 expression correlated with outcome in PDAC patients treated with gemcitabine. Modulation of apoptosis, Akt phosphorylation, and expression of genes involved in invasive behavior may contribute to the role of miR-21 in gemcitabine chemoresistance and to the rational development of new targeted combinations. Cancer Res; 70(11); 4528-38. ©2010 AACR.

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Section: Introductionmentioning

confidence: 99%

MicroRNA-21 in Pancreatic Cancer: Correlation with Clinical Outcome and Pharmacologic Aspects Underlying Its Role in the Modulation of Gemcitabine Activity

et al. 2010

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“…12 Tremendous evidence has shown that various types of miRNAs participate in the regulation of many biological processes, 13,14 affect cancer prognosis 15 and influence the host response to chemotherapy. 16,17 MiR-181b was decreased significantly in human multidrug-resistant leukemia cells and increased the sensitivity of leukemia cells to cytotoxic chemotherapeutic agents. 18 MiR-381 and miR-495 modulated the MDR phenotype of leukemia K562/ ADM cells and were associated inversely with the expression of the MDR1 gene and its protein product, P-glycoprotein.…”

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confidence: 99%

Alpha-2, 3-sialyltransferases regulate the multidrug resistance of chronic myeloid leukemia through miR-4701-5p targeting ST3GAL1

Luo

Dong

et al. 2016

Laboratory Investigation

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The aberrant sialylation profile on the surface of leukemia cells has been recognized for its potential diagnostic value towards assessing leukemia multidrug resistance (MDR). MicroRNAs as endogenous regulators of gene expression have been implicated in treating MDR. In this study, we describe the differential expressional profiles of α-2, 3-sialyltransferases (ST) and miR-4701-5p in three pairs of chronic myeloid leukemia (CML) cell lines and 48 clinical samples of bone marrow mononuclear cells from CML patients. The altered expression level of ST3GAL1 was found corresponding to the drugresistant phenotype (with and without adriamycin resistance) of CML cell lines both in vitro and in vivo. Further the results showed that miR-4701-5p directly targeted ST3GAL1 to reduce CML cells resistance to multiple chemotherapeutics in vitro and to convert tumor cells from adriamycin resistant to susceptible in vivo of mice. These results indicate that differential expression of α-2,3 ST is involved in MDR of CML, and that miR-4701-5p regulates the susceptibility of CML cells to multiple drugs, at least in part, through targeting ST3GAL1.

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“…The emergence of the term pharmacogenomics was possible after the availability of the human haplotype map (HapMap) and of highthroughput genotyping platforms that have been facilitating more systematic genetic screens for new and clinically important drug targets. (Passetti et al, 2009) Therefore the concept of pharmacogenomics has progressively evolved from pharmacogenetics and expands beyond monogenic pharmacokinetics traits, making also the transition from associative genetic studies based on candidate gene hypothesis towards genome-wide association/screening studies (GWAS) in order to identify genetic biomarkers with prognostic role for disease progression and predictive capacity for drug responsiveness.…”

Section: Pharmacogenomics' Scope and Goalsmentioning

confidence: 99%

Pharmacogenetics: Matching the Right Foundation at Personalized Medicine in the Right Genomic Era

Taușer¹

2012

Clinical Applications of Pharmacogenetics

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The impact of microRNAs and alternative splicing in pharmacogenomics

Cited by 54 publications

References 131 publications

MicroRNA-21 in Pancreatic Cancer: Correlation with Clinical Outcome and Pharmacologic Aspects Underlying Its Role in the Modulation of Gemcitabine Activity

MicroRNA-21 in Pancreatic Cancer: Correlation with Clinical Outcome and Pharmacologic Aspects Underlying Its Role in the Modulation of Gemcitabine Activity

Alpha-2, 3-sialyltransferases regulate the multidrug resistance of chronic myeloid leukemia through miR-4701-5p targeting ST3GAL1

Pharmacogenetics: Matching the Right Foundation at Personalized Medicine in the Right Genomic Era

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