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Dysregulation of miR-335-3p, targeted by NEAT1 and MALAT1 long non-coding RNAs, is associated with poor prognosis in childhood acute lymphoblastic leukemia

Pouyanrad, Shahrzad, Rahgozar, Soheila, Ghodousi, Elaheh Sadat
Gene 2019 v.692 pp. 35-43
ABC transporters, biomarkers, bone marrow, childhood, children, drug therapy, gene expression, lymphocytic leukemia, messenger RNA, multiple drug resistance, non-coding RNA, patients, prognosis, reverse transcriptase polymerase chain reaction
Acute lymphoblastic leukemia (ALL) is the most prevalent cancer among children, and multidrug efflux mediated by overexpression of ABC transporters is the major impediment to successful chemotherapy in this malignancy. The goal of this study is to identify the non-coding RNAs (ncRNAs) which may affect the expression levels of ABCA3; the previously identified prognostic biomarker for multidrug resistance (MDR) in childhood ALL (cALL). Bone marrow samples from 64 cALLs, including 46 de novo and 18 relapsed patients, in addition to 30 non-cancer controls were collected, and ncRNAs were nominated using in silico studies. Quantitative RT-PCR showed low expression profiles of miR-335-3p in cALLs compared with the control group (P = 0.018). Inverse correlation was determined between the miR-335-3p and ABCA3 mRNA expression profiles in cALL patients (r = 0.5019, P = 0.002). Moreover, it was shown that the expression levels of miR-335-3p was downregulated in the drug-resistant samples (MDR group) compared with the drug-sensitive patients (mrd− group), (P = 0.0005, AUC = 0.801). On the other hand, negative correlations were identified between the expression levels of miR-335-3p and the selected LncRNAs, NEAT1 and MALAT1, in the MDR group compared with the mrd− patients (P = 0.009), suggesting a sponge effect for these LncRNAs. The current study showed a potential regulatory role for miR-335-3p in ABCA3 expression targeted by NEAT1 and MALAT1 long non-coding RNAs. This negative impact may possibly contribute to the development of chemoresistance in childhood ALL, and provide an exceptional insight to new therapeutic approaches.