Circulating microRNA-192 as a diagnostic biomarker in human chronic lymphocytic leukemia

Abstract

Chronic lymphocytic leukemia (CLL) is known as the most common lymphoid malignancy in the Western world. MicroRNAs (miRNAs) are a class of small noncoding RNAs with pivotal roles in cellular and molecular processes related to different malignancies including CLL. Recently, some studies have shown that miR-192 plays a key role in CLL pathogenesis through increasing CDKN1A/p21 levels, suppression of Bcl-2 and enhancement of wild-type P53 and cell cycle arrest. Forty samples, including 20 patients with CLL, diagnosed in Omid hospital (Isfahan, Iran) and 20 healthy controls were sampled during a period of 4 months. Using real-time PCR method, expression of miR-192 was analyzed in peripheral blood mononuclear cells (PBMCs) of CLL patients in comparison with healthy subjects. In silico molecular signaling pathway enrichment analysis was also performed on validated and predicted targets (targetome) of miR-192 in DAVID database to explore possible role of miR-192 in some pathways. The expression of miR-192 was found to be significantly reduced (~2.5-folds) in CLL patients compared with healthy subjects (P=0.002). In silico molecular signaling pathway enrichment analysis detected cell indicated signaling pathway as one of the most statistically relevant pathway with miR-192 targetome. Our findings showed that miR-192 could be a biomarker for early diagnosis of CLL.

Angiogenesis biomarkers and their targeting ligands as potential targets for tumor angiogenesis

“…These molecules are small non‐coding RNA which act as negative/positive regulators in many types of biological processes such as angiogenesis (Hoseini et al, ; Mirzaei, ; Mirzaei, Khataminfar, et al, ; Mirzaei, Sahebkar, Jaafari, Goodarzi, & Mirzaei, ; Mirzaei, Yazdi, Salehi, & Mirzaei, ; Rashidi, Hoseini, Sahebkar, & Mirzaei, ; Saadatpour et al, ). It has been showed that deregulation of them via targeting a sequence cellular and molecular pathways (e.g., MAPK, Akt, VEGF, and AP‐1) lead to initiation and development of various cancers (Figure ) (Fathullahzadeh, Mirzaei, Honardoost, Sahebkar, & Salehi, ; Mohammadi, Goodarzi, Jaafari, Mirzaei, & Mirzaei, ; Reza Mirzaei et al, ; Salarinia et al, ; Simonian, Mosallayi, & Mirzaei, ). A large number studies indicated that deregulation of various miRNAs (e.g., miR‐124, miR‐155, miR‐378, miR‐17‐92 cluster, miR‐15, and miR‐16) are involved in induction/inhibition of angiogenesis in various types of cells such as cancer cells (Gallach, Calabuig‐Fariñas, Jantus‐Lewintre, & Camps, ; Landskroner‐Eiger, Moneke, & Sessa, ).…”

MicroRNAs and response to therapy in leukemia

“…Epigenetic therapy in cancer refers to the targeting of epigenetic aberrations, which mainly depend on DNMT and histone deacetylase (HDAC) inhibitors. There is some evidence of treating some types of hematopoietic cancers, including MDS, multiple myeloma and several lymphomas . The recent results in the treatment of solid tumors with the help of epigenetic therapy are contradictory and the mechanisms are unclear .…”

Pancreatic β‐cell regeneration: From molecular mechanisms to therapy

“…Among the various epigenetic players, miRNAs have appeared as new and critical players in various physiological and pathological events. MiRNAs are a type of short noncoding RNAs and act as epigenetic controllers that enable the regulation of a variety of biological processes, such as angiogenesis, growth, differentiation, metastasis, and so on . Deregulation of miRNAs is related to the initiation and progression of many diseases such as cancer, cardiovascular diseases, stroke, neurogenerative diseases, depression, and diabetes .…”