MicroRNA-mRNA Pairs Associated with Outcome in AML: From in vitro Cell-based Studies to AML Patients

Cytarabine is the primary chemotherapeutic agent used for treatment of AML. Disease relapse after initial remission remains one of the most pressing therapeutic challenges in the treatment of AML. Relapsed disease is often resistant to cytarabine and subsequent salvage therapy is ineffective. Recent...

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Main Authors: Neha S Bhise (Author), Lata eChauhan (Author), Miyoung eShin (Author), Xueyuan eCao (Author), Stanley ePounds (Author), Vishal eLamba (Author), Jatinder K Lamba (Author)
Format: Book
Published: Frontiers Media S.A., 2016-01-01T00:00:00Z.
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700 1 0 |a Lata eChauhan  |e author 
700 1 0 |a Miyoung eShin  |e author 
700 1 0 |a Xueyuan eCao  |e author 
700 1 0 |a Stanley ePounds  |e author 
700 1 0 |a Vishal eLamba  |e author 
700 1 0 |a Jatinder K Lamba  |e author 
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520 |a Cytarabine is the primary chemotherapeutic agent used for treatment of AML. Disease relapse after initial remission remains one of the most pressing therapeutic challenges in the treatment of AML. Relapsed disease is often resistant to cytarabine and subsequent salvage therapy is ineffective. Recent studies have shown that some miRNAs are associated with prognosis but have not yet explored the role of miRNAs in cellular response to cytarabine. We identified 20 miRNAs that associate with the in vitro cytarabine chemo-sensitivity or apoptotic response of eight AML cell lines. Out of the 20 miRNA, data on 18 miRNAs was available in AML patients from TCGA database. Our stepwise-integrated analyses (step 1- microRNA-target mRNA that were significantly correlated in AML patients; step -2 mRNAs from step 1 with significant association with overall survival (OS) identified 23 unique miRNA-mRNA pairs predictive of OS in AML patients. As expected HOX genes (HOXA9, HOXB7 and HOXA10) were identified to be regulated by miRs as well as predictive of worse OS. Additionally, miR107-Myb, miR-378-granzyme B involved in granzyme signaling and miR10a-MAP4K4 were identified to be predictive of outcome through integrated analysis. Although additional functional validations to establish clinical/pharmacologic importance of microRNA-mRNA pairs are needed, our results from RNA EMSA confirmed binding of miR-10a, miR-378 and miR-107 with their target genes GALNT1, GZMB and MYB respectively. Integration of pathogenic and pharmacologically significant microRNAs and microRNA-mRNA relationships identified in our study opens up opportunities for development of targeted/microRNA-directed therapies. 
546 |a EN 
690 |a Cytarabine 
690 |a Gene Expression 
690 |a microRNA 
690 |a miRNA 
690 |a Acute Myeloid Leukemia 
690 |a Therapeutics. Pharmacology 
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786 0 |n Frontiers in Pharmacology, Vol 6 (2016) 
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