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.
Early diagnostic is one of the most important steps in cancer therapy which helps to design and choose a better therapeutic approach. The finding of biomarkers in various levels including genomics, transcriptomics, and proteomics levels could provide better treatment for various cancers such as chronic lymphocytic leukemia (CLL). The CLL is the one of main lymphoid malignancies which is specified by aggregation of mature B lymphocytes. Among different biomarkers (e.g., CD38, chromosomes abnormalities, ZAP-70, TP53, and microRNA [miRNA]), miRNAs have appeared as new diagnostic and therapeutic biomarkers in patients with the CLL disease. Multiple lines of evidence indicated that deregulation of miRNAs could be associated with pathological events which are present in the CLL. These molecules have an effect on a variety of targets such as Bcl2, c-fos, c-Myc, TP53, TCL1, and STAT3 which play critical roles in the CLL pathogenesis. It has been shown that expression of miRNAs could lead to the activation of B cells and B cell antigen receptor (BCR). Moreover, exosomes containing miRNAs are one of the other molecules which could contribute to BCR stimulation and progression of CLL cells. Hence, miRNAs and exosomes released from CLL cells could be used as potential diagnostic and therapeutic biomarkers for CLL. This critical review focuses on a very important aspect of CLL based on biomarker discovery covers the pros and cons of using miRNAs as important diagnostics and therapeutics biomarkers for this deadly disease.
: Long noncoding RNAs (lncRNAs) constitute large portions of the mammalian transcriptome which appeared as a fundamental player, regulating various cellular mechanisms. LncRNAs do not encode proteins, have mRNA-like transcripts and frequently processed similar to the mRNAs. Many investigations have determined that lncRNAs interact with DNA, RNA molecules or proteins and play a significant regulatory function in several biological processes, such as genomic imprinting, epigenetic regulation, cell cycle regulation, apoptosis, and differentiation. LncRNAs can modulate gene expression on three levels: chromatin remodeling, transcription, and post-transcriptional processing. The majority of the identified lncRNAs seem to be transcribed by the RNA polymerase II. Recent evidence has illustrated that dysregulation of lncRNAs can lead to many human diseases, in particular, cancer. The aberrant expression of lncRNAs in malignancies contributes to the dysregulation of proliferation and differentiation process. Consequently, lncRNAs can be useful to the diagnosis, treatment, and prognosis, and have been characterized as potential cancer markers as well. In this review, we highlighted the role and molecular mechanisms of lncRNAs and their correlation with some of the cancers.
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