Long Non-Coding RNAs Guide the Fine-Tuning of Gene Regulation in B-Cell Development and Malignancy

Int J Mol Sci. 2018 Aug 21;19(9):2475. doi: 10.3390/ijms19092475.

Abstract

With the introduction of next generation sequencing methods, such as RNA sequencing, it has become apparent that alterations in the non-coding regions of our genome are important in the development of cancer. Particularly interesting is the class of long non-coding RNAs (lncRNAs), including the recently described subclass of circular RNAs (circRNAs), which display tissue- and cell-type specific expression patterns and exert diverse regulatory functions in the cells. B-cells undergo complex and tightly regulated processes in order to develop from antigen naïve cells residing in the bone marrow to the highly diverse and competent effector cells circulating in peripheral blood. These processes include V(D)J recombination, rapid proliferation, somatic hypermutation and clonal selection, posing a risk of malignant transformation at each step. The aim of this review is to provide insight into how lncRNAs including circRNAs, participate in normal B-cell differentiation, and how deregulation of these molecules is involved in the development of B-cell malignancies. We describe the prognostic value and functional significance of specific deregulated lncRNAs in diseases such as acute lymphoblastic leukemia, chronic lymphocytic leukemia, mantle cell lymphoma, diffuse large B-cell lymphoma, follicular lymphoma, Burkitt lymphoma and multiple myeloma, and we provide an overview of the current knowledge on the role of circRNAs in these diseases.

Keywords: B-cell development; acute lymphoblastic leukemia (ALL); burkitt lymphoma (BL); chronic lymphocytic leukemia (CLL); circular RNA; diffuse large B-cell lymphoma (DLBCL); gene regulation; long non-coding RNA; mantle cell lymphoma (MCL); multiple myeloma (MM).

Publication types

  • Review

MeSH terms

  • B-Lymphocytes / immunology
  • B-Lymphocytes / pathology*
  • Burkitt Lymphoma / genetics
  • Burkitt Lymphoma / immunology
  • Burkitt Lymphoma / pathology
  • Cell Differentiation
  • Cell Transformation, Neoplastic / genetics*
  • Cell Transformation, Neoplastic / immunology
  • Cell Transformation, Neoplastic / pathology
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics
  • Leukemia, Lymphocytic, Chronic, B-Cell / immunology
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology
  • Lymphoma, Follicular / genetics
  • Lymphoma, Follicular / immunology
  • Lymphoma, Follicular / pathology
  • Lymphoma, Large B-Cell, Diffuse / genetics*
  • Lymphoma, Large B-Cell, Diffuse / immunology
  • Lymphoma, Large B-Cell, Diffuse / pathology
  • Lymphoma, Mantle-Cell / genetics
  • Lymphoma, Mantle-Cell / immunology
  • Lymphoma, Mantle-Cell / pathology
  • Multiple Myeloma / genetics
  • Multiple Myeloma / immunology
  • Multiple Myeloma / pathology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / immunology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • RNA / genetics
  • RNA / immunology
  • RNA, Circular
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / immunology
  • Signal Transduction

Substances

  • RNA, Circular
  • RNA, Long Noncoding
  • RNA