Increased level of long non coding RNA H19 is correlated with the downregulation of miR-326 and BCL-2 genes in pediatric acute lymphoblastic leukemia, a possible hallmark for leukemogenesis.

Long non-coding RNAs (lncRNAs) and their role in competitive endogenous RNA (ceRNA) networks have emerged as fundamental debates in the biological processes of initiation and progression of cancer. This study aimed to identify and measure the expression levels of relevant ceRNA regulatory genes contributing to acute lymphoblastic leukemia (ALL). lncRNA H19 and BCL-2 mRNA were chosen based on in silico studies and their interactions with miR-326. Subsequently, the aforementioned coding/non-coding gene expression profiles were measured using qRT-PCR in 50 bone marrow samples, including 33 cases with pediatric ALL and 17 controls with no evidence of malignancy. lncRNA H19 was identified as an oncogenic factor which was noticeably increased in the newly diagnosed patients (P = 0.0019, AUC = 0.84) and negatively associated with miR-326 (r = -0.6, P = 0.02). Furthermore, a negative correlation was introduced between the transcriptional levels of miR-326 and the anti-apoptotic BCL-2 gene (r = -0.6, P = 0.028). The novel experimental and bioinformatic results achieved in this study may provide new insights into the molecular leukemogenesis of pediatric ALL.

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

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.