Long non-coding RNAs and MYC association in hematological malignancies
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REVIEW ARTICLE
Long non-coding RNAs and MYC association in hematological malignancies Leonidas Benetatos 1
&
Agapi Benetatou 2 & Georgios Vartholomatos 3
Received: 2 March 2020 / Accepted: 29 June 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Long non-coding RNAs (lncRNAs) have an established role in cell biology. Among their functions is the regulation of hematopoiesis. They characterize the different stages of hematopoiesis in a more lineage-restricted expression pattern than coding mRNAs. They affect hematopoietic stem cell renewal, proliferation, and differentiation of committed progenitors by interacting with master regulators transcription factors. Among these transcription factors, MYC has a prominent role. Similar to MYC’s transcriptional activation/amplification of protein coding genes, MYC also regulates lncRNAs’ expression profile, while it is also regulated by lncRNAs. Both myeloid and lymphoid malignancies are prone to the association of MYC with lncRNAs. Such interaction inhibits apoptosis, enhances cell proliferation, deregulates metabolism, and promotes genomic instability and resistance to treatment. In this review, we discuss the recent findings that encompass the crosstalk between lncRNAs and describe the pathways that very probably have a pathogenetic role in both acute and chronic hematologic malignancies. Keywords MYC . Long non-coding RNAs . AML . Lymphoma . Multiple myeloma . microRNAs . ceRNAs
Long non-coding RNAs: general concepts Most of the scientific data on cancer biology focus on protein coding genes (PCGs) while the role of long non-coding RNAs (lncRNAs) has recently emerged and is not completely understood. LncRNAs are > 200 nt long, not translated into proteins, and they can regulate transcription through different mechanisms. LncRNA genes may generate different transcripts, and to date, nearly 57,000 lncRNAs generating 127,800 transcripts are included in the LNCipedia v5.2 database, whereas the NONCODE v5 database includes more than 96,000 human lncRNAs corresponding to more than 172,200 transcripts. Several reviews discussing their localization, transcription control, and other biological and functional characteristics have been published [1–6].
* Leonidas Benetatos [email protected] 1
Blood Bank, Preveza General Hospital, 48100 Preveza, Greece
2
Department of Pharmacy, School of Health Sciences, University of Patras, Patras, Greece
3
Molecular Biology Laboratory, Ioannina University Hospital, Ioannina, Greece
LncRNAs have an established role in both physiological development and pathological processes. They have different roles during different stages of cell identity establishment, and they are also implicated in reprogramming of somatic cells to induce pluripotent stem cells [7–11]. Similar to PCGs, lncRNAs affect hallmarks of cancer acting as driver genes during oncogenesis through their functional effectors [12, 13]. LncRNAs exhibit tumor-suppressive or oncogenic function in 29% and 63% of the cases, respectively, whereas 8% ex
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