Long non-coding RNA: The functional regulator of mesenchymal stem cells

Abstract

Mesenchymal stem cells (MSCs) are a subset of multipotent stroma cells residing in various tissues of the body. Apart from supporting the hematopoietic stem cell niche, MSCs possess strong immunoregulatory ability and multiple differentiation potentials. These powerful capacities allow the extensive application of MSCs in clinical practice as an effective treatment for diseases. Therefore, illuminating the functional mechanism of MSCs will help to improve their curative effect and promote their clinical use. Long noncoding RNA (LncRNA) is a novel class of noncoding RNA longer than 200 nt. Recently, multiple studies have demonstrated that LncRNA is widely involved in growth and development through controlling the fate of cells, including MSCs. In this review, we highlight the role of LncRNA in regulating the functions of MSCs and discuss their participation in the pathogenesis of diseases and clinical use in diagnosis and treatment.

Keywords: Long non-coding RNA; Mesenchymal stem cells; Multipotent stroma cells; Regulator.

Figure 1

Long non-coding RNA in the tri-lineage differentiation of mesenchymal stem cells. Mesenchymal stem cells possess the capacity for osteogenic, chondrogenic and adipogenic differentiation, and many long non-coding RNAs play an important role in this process. MSCs: Mesenchymal stem cells; LncRNA: Long non-coding RNA; HOTAIR: HOX transcript antisense RNA; GAS5: Growth arrest specific 5; MEG3: Maternally expressed 3; BMNCR: Bone marrow stem cell–related LncRNA; GAS5: Growth arrest specific 5; ROCR: Regulator of chondrogenesis RNA; DANCR: Differentiation antagonizing non-protein coding RNA; ZBED3-AS1: Zinc finger BED-type containing 3 antisense RNA 1; HULC: LncRNA-highly upregulated in liver cancer; MALAT: Metastasis-associated lung adenocarcinoma transcript; BDNF-AS: Brain-derived neurotrophic factor antisense.

Figure 2

Mesenchymal stem cells in ankylosing spondylitis. Mesenchymal stem cells (MSCs) from ankylosing spondylitis (AS) patients (AS-MSCs) have lower immunoregulation ability, resulting in an imbalance between Th17 cells and Treg cells. In addition, AS-MSCs secreted more BMP2 but less Noggin, leading to their enhanced osteogenic differentiation ability. LncRNA-ZNF354A, Lin54, FRG2C and USP50 were involved in this dysfunction. The disorders of AS-MSCs resulted in chronic inflammation and pathological osteogenesis in the axial skeleton of AS patients. MSCs: Mesenchymal stem cells; AS: Ankylosing spondylitis; LncRNA: Long non-coding RNA; BMP: Bone morphogenetic protein.