Regulation of the expression of zinc finger protein genes by microRNAs enriched within acute lymphoblastic leukemia-derived microvesicles

Abstract

ABSTRACT. Microvesicles (MVs) are submicrometric membrane fragments that can "engulf" cytoplasmic contents such as microRNAs (miRNAs) from their cellular origin. The study of miRNAs carried within MVs might provide insights into the roles that miRNAs play in the underlying pathophysiologic processes of acute lymphoblastic leukemia (ALL). We identified numerous dysregulated MV miRNAs in patients with B-and T-cell ALL by using Agilent microarray analysis. Selected miRNAs obtained by microarray profiling were validated using quantitative reverse transcription-polymerase chain reaction. Using bioinformatic tools, we found that 118 and 116 miRNAs from Band T-ALL MVs, respectively, regulated the expression of zinc finger protein (ZFP) genes. For example, zinc finger protein 238 (ZNF238), known as a tumor suppressor, was regulated by miR-20b over-expression. Conversely, ZNF267, a cancer-promoting factor, was mediated by downregulated miR-23a and miR-23b. Considering that miRNAs are generally believed to repress gene expression, antineoplastic ZNF238 was likely inhibited while the level of oncogenic ZNF267 was likely increased by miRNA dysregulation, leading to modification of the ALL microenvironment. In addition, gene ontology and signaling pathway analysis demonstrated that a subset of the ZFP genes targeted by altered MV miRNAs are involved in cellular biological processes including proliferation, differentiation, apoptosis, and cell cycle regulation. These findings indicated that cancer-associated MV miRNAs and their target ZFP genes might be novel pathogenic factors in ALL. However, the specific roles exerted by MV miRNAs and their target ZFP genes on the pathological mechanisms of ALL remain to be further understood.

Long noncoding RNA ZNF667‐AS1 reduces tumor invasion and metastasis in cervical cancer by counteracting microRNA‐93‐3p‐dependent PEG3 downregulation

“…The pattern of competitive combination between ZNFs and miRNAs has been noted in many reports. Anticancer ZNF238 is repressed by miR‐20b overexpression whereas ZNF24, a tumor promoter, is increased by miR‐940 dysregulation (Lu et al , ). In clear cell renal cell carcinoma cells, miR‐93‐3p was found to decrease the expression of pigment epithelium‐derived factor (PEDF) and inhibit osteogenesis (Wang et al , ).…”

microRNA-23a in Human Cancer: Its Roles, Mechanisms and Therapeutic Relevance

“…Lu et al identified that the miR-23a in MVs secreted by acute lymphocytic leukemia (ALL) cells regulated the expression of zinc finger protein 267 (ZNF267), an oncogenic factor [111]. This further led to the alteration of the cellular signaling process involved in proliferation, differentiation, apoptosis, and cell cycle regulation.…”

Exosomes derived from human placental MSCs carrying miR-4450 inhibitor alleviate intervertebral disc degeneration and ameliorate gait disturbances via up-regulation of ZNF121

“…For example, Lu et al found that 118 and 116 miRNAs from B and T acute lymphoblastic leukemia microvesicles regulated ZNF gene expressions, respectively. Besides, gene ontology and signaling pathway analysis indicated that the altered microvesicle miRNAs targeted a subset of ZNF genes and participated in cell biology processes, including differentiation, proliferation, apoptosis, and cell cycle regulation [35]. We further studied the function of EXO-antagomiR-4450 in the IDD mouse model.…”