Non-Coding RNAs as Cancer Hallmarks in Chronic Lymphocytic Leukemia

Abstract

The discovery of non-coding RNAs (ncRNAs) and their role in tumor onset and progression has revolutionized the way scientists and clinicians study cancers. This discovery opened new layers of complexity in understanding the fine-tuned regulation of cellular processes leading to cancer. NcRNAs represent a heterogeneous group of transcripts, ranging from a few base pairs to several kilobases, that are able to regulate gene networks and intracellular pathways by interacting with DNA, transcripts or proteins. Deregulation of ncRNAs impinge on several cellular responses and can play a major role in each single hallmark of cancer. This review will focus on the most important short and long non-coding RNAs in chronic lymphocytic leukemia (CLL), highlighting their implications as potential biomarkers and therapeutic targets as they relate to the well-established hallmarks of cancer. The key molecular events in the onset of CLL will be contextualized, taking into account the role of the “dark matter” of the genome.

Non-Coding RNAs: The “Dark Side Matter” of the CLL Universe

“…Moreover, also miR-34a is frequently down-regulated in CLL [ 19 ], both miR-34a and miR-34b/c are P53 targets [ 20 ]. Consequently, P53 induces apoptosis by partially activation the miR-34-BCL2 axis, and the loss of expression of these miRNAs is associated with resistance against P53-mediated apoptosis [ 9 , 20 ].…”

“…For example, the miR-17/92 cluster is up-regulated in unmutated IGHV CLL [ 21 ]. In this case, the increased B-cell receptor (BCR) activation induces MYC expression that drives miR-17/92 expression [ 9 , 22 ]. In turn, this cluster regulates cell cycle progression and proliferation through several targets including CDKN1a, E2F5, IKAROS, PTEN, STATs, TP53INP1, and ZBTB4 [ 9 , 22 ].…”

“…However, the biological behavior of CLL as well as the response to treatments does not always correlate with genomic alterations [ 9 ]. It has been shown that almost 20% of CLL patients do not present chromosomal aberrations [ 9 ].…”

“…However, the biological behavior of CLL as well as the response to treatments does not always correlate with genomic alterations [ 9 ]. It has been shown that almost 20% of CLL patients do not present chromosomal aberrations [ 9 ]. Other events, such as epigenetic changes and non-coding RNA (ncRNA) alterations, have been reported as possible causes of the outcome of the disease [ 9 ].…”

“…It has been shown that almost 20% of CLL patients do not present chromosomal aberrations [ 9 ]. Other events, such as epigenetic changes and non-coding RNA (ncRNA) alterations, have been reported as possible causes of the outcome of the disease [ 9 ]. Over the past decade, several studies have identified deregulated ncRNAs in CLL [ 10 ].…”