Altered expression pattern of miR-29a, miR-29b and the target genes in myeloid leukemia

Abstract

ObjectivesThe miR-29 family have been demonstrated acting as vital tumor suppressor in multiple cancers as well as regulators in the adaptive immune system. Little is known about their role in leukemogenesis. The purpose of this study is to analyze the expression pattern of miR-29a/29b and its target genes Mcl-1 (myeloid cell leukemia sequence 1) and B-cell lymphoma 2 (Bcl-2) in myeloid leukemia.MethodsQuantitative real-time PCR was used for detecting genes expression level in peripheral blood mononuclear cells (PBMCs) from 10 cases with newly diagnosed, untreated acute myeloid leukemia (AML) and 14 cases with newly diagnosed, untreated chronic myeloid leukemia (CML) in chronic phase, and 14 healthy individual (HI) served as controls. Correlation between the relative expression levels of different genes have been analyzed.ResultsSignificant lower expression of miR-29a/29b and higher expression level of two potential target genes Bcl-2 and Mcl-1 were found in PBMCs from AML and CML patients compared with HI group. In addtion, miR-29a expression in AML was significantly lower than that in CML. Moreover, negative correlation between miR-29a/29b and its target genes have been found. While, positive correlation between relative expression level of miR-29a and miR-29b or Bcl-2 and Mcl-1 were presented in the total 38 research objects.ConclusionDown-regulated miR-29a and miR-29b, and accompanying up-regulated Bcl-2 and Mcl-1 are the common feature in myeloid leukemias. These data further support the role for miR-29a/29b dysregulation in myeloid leukemogenesis and the therapeutic promise of regulating miR-29a/29b expression for myeloid leukemia in the future.

Assessment of the Diagnostic Potential of miR-29a-3p and miR-92a-3p as Circulatory Biomarkers in Acute Myeloid Leukemia

“…We observed that there is a significant downregulation of mir29a-3p and mir92a-3p in the bone marrow aspirates and the plasma of the newly diagnosed AML patients when compared to normal subjects; (p <0.001). Similar Results were reported by other study groups (Zhu et al, 2013;Gong et al, 2014;Xu et al, 2014) who reported a downregulation in miR-29a/29b levels in peripheral blood mononuclear cells and bone marrow from AML patients compared with healthy individuals. Also, miR-29a was found to be downregulated in many other types of neoplasms like lung cancer (Barkley and Santocanale, 2013), oral squamous carcinoma (Lu et al, 2014), glioblastoma (Xi et al, 2017), metastatic prostate cancer (Ahmed et al, 2013), ALK-positive anaplastic large cell lymphomas (Desjobert et al, 2011), endocrine-sensitive breast cancer (Muluhngwi et al, 2017).…”

“…In case of miR-29, this microRNA family may target many transcription factors and anti-apoptotic genes (Si et al, 2013). Myeloid cell leukemia sequence1 (MCL1) has been identified as a potent target gene of miR-29a and miR-92a (Xu et al, 2014). Mcl-1 belongs to Bcl-2 family which considered an important player in regulation of apoptosis and any change in their expression levels will lead to the progression of human cancer (Thomas et al, 2010;Kadia et al, 2019).…”

Expression pattern of key microRNAs in patients with newly diagnosed chronic myeloid leukemia in chronic phase

“…Overexpression of miR-126 in acute myeloid leukemia (AML) patients associated with poor survival, and inhibition of miR-126 eradicates the CD34 + 38 À stem/progenitor cells in AML Tumor suppressor Upregulated [39,40,41] target sites were further studied according to the PCT values from the TARGETSCAN version 5.1. The target genes are involved in signaling pathways such as MAP kinase, transforming growth factor b, TP53 (p53), ErbB, and RUNX1, which are involved in HSC differentiation [42].…”

Small Non-Coding RNAs in Regulation of Course and Therapeutic Efficacy in Acute Myeloid Leukemia

“…miRNA-29b downregulates DNMT1 indirectly by targeting Sp1, a trans-activator of the DNMT1 gene due to a decrease in global DNA methylation and re-expression of p15 (INK4b) and ESR1. Moreover, miRNA-29 family members may downregulate the active DNA demethylation pathway members tet-methylcytosine dioxygenase (TET1) and thymine DNA glycosylase (TDG) [37,60]. miRNA-29 targets CCNT2 that is a component of the positive transcription elongation factor b (P-TEFb).…”