Table 2

Characterization of functional islet lncRNAs

lncRNAsExpressionFunctionReference
PVT1Human mesangial cellsPVT1 mediates the development and progression of diabetic nephropathy through mechanisms involving extracellular matrix accumulation.Alvarez et al., 2011 (29)
HI-LNC25Enriched in human islets and purified β-cells compared with other tissuesPositively regulates GLIS3 (which contains both T1D and T2D risk variants) in EndoC-βΗ1 human β-cell line.Morán et al., 2012 (28)
LINC01611Human islets from patients with T2DSNP (rs9362054) associated with diabetic retinopathy mapped to this lncRNA.Awata et al., 2014 (31)
MALAT1Upregulated in retinas of diabetic (streptozotocin or db/db) miceUpregulation of MALAT1 is associated with microvascular dysfunction. MALAT1 KD alleviates diabetic retinopathy.Liu et al., 2014 (66)
DEANR1Definitive endoderm differentiated from human embryonic stem cellsPositively regulates expression of the endoderm factor FOXA2 by facilitating SMAD2/3 recruitment to the FOXA2 promoter.Jiang et al., 2015 (48)
lncRNAs 1, 2, 3, 4Increased expression in MIN6 cells exposed to cytokines and NOD miceOverexpression in MIN6 cells increased apoptosis (lncRNAs 1–4) and caused nuclear translocation of p65 (lncRNA 1).Motterle et al., 2015 (52)
Tug1Enriched in mouse islets compared with other tissues, downregulated in NOD isletsDownregulation of lncRNA TUG1 expression increased apoptosis and reduced insulin secretion in mouse β-cells.Yin et al., 2015 (50)
βlinc1 (HI-LNC15)Restricted expression in mouse β-cellsRegulates β-cell identity and function in vivo, partially through the regulation of its neighboring gene Nkx2–2.Arnes et al., 2016 (49)
NONHSAG011351Human islets with T1D-associated SNPsrs705708 had a cis-eQTL effect on both ERBB3 and NONHSAG011351, causing reduced expression of both genes.Kaur et al., 2016 (67)
Meg3Enriched in mouse islets compared with other tissues, downregulated in db/db isletsKD in MIN6 cells causes impaired β-cell function and increased apoptosis.You et al., 2016 (51)
lncRNA-RORReduced expression during differentiation of human amniotic epithelial cells into β-like cellsLoss of lncRNA-ROR during differentiation impairs β-cell function and reduced expression of Insulin, Pdx1, and Glut2.Zou et al., 2016 (57)
PLUTO (HI-LNC71)Enriched in human islets and purified β-cells relative to the exocrine pancreas and nonpancreatic tissuesRegulates transcription of the nearby gene PDX1 and influences 3D chromatin structure surrounding PDX1.Akerman et al., 2017 (39)
TUNAR (HI-LNC78)Enriched in human islets and purified β-cells relative to the exocrine pancreas and nonpancreatic tissuesKD of TUNAR caused impaired glucose-stimulated insulin secretion.Akerman et al., 2017 (39)
βlinc2, βlinc3Restricted expression in mouse β-cells, increased (βlinc2) or decreased (βlinc3) expression in mice given high-fat diet and db/db isletsUpregulation of βlinc2 caused increased apoptosis in MIN6 cells and isolated islets.Motterle et al., 2017 (46)