Long Noncoding RNAs in Diffuse Large B-Cell Lymphoma: Current Advances and Perspectives

Figures & data

Figure 1 Classification of lncRNAs according to the GENCODE v7 catalogue. (A) Intergenic lncRNAs are located between two coding genes and can be transcribed from either the same strand or antisense in a divergent or convergent manner. (B) Genic lncRNAs include three subtypes: exonic lncRNAs, which intersect a protein-coding gene by at least 1 bp; intronic lncRNAs, which reside within the intron of a protein-coding gene in either the sense or antisense direction; and overlapping lncRNAs, which contain a protein-coding gene within an intron in either the sense or antisense direction.

Figure 2 Brief overview of lncRNA functions based on interactions with various intracellular molecules. (A) LncRNA can interact with chromatin. (B) LncRNA can interact with mRNA and miRNA. (C) LncRNA can interact with protein.

Table 1 Examples of lncRNAs with Prognostic and/or Functional Impact in DLBCL

lncRNAs	Putative Roles	Expression	Direct Targets	Proposed Functions	Prognostic Impact	References
HOTAIR	Oncogenic	Upregulated	Not assessed	Promotes cell growth and inhibits apoptosis by epigenetic regulating H3K27me3 and activating the PI3K/AKT/NF-κB pathway	Poor	[^Citation34^–^Citation36]
FIRRE	Oncogenic	Upregulated	Not assessed	Is transcriptionally activated by MYC proto-oncogene and activates Wnt/β-catenin signaling to facilitate cell growth via modulation of the nuclear translocation of β-catenin	Poor	[^Citation37]
NEAT1_1	Oncogenic	Upregulated	Not assessed	Promotes cell proliferation and migration	Poor	[^Citation38]
RP11-513G11.1	Oncogenic	Upregulated	Not assessed	Not assessed	Poor	[^Citation39]
NONHSAG026900	Tumor suppressor	Downregulated	Not assessed	Not assessed	Favorable	[^Citation40]
PANDA	Tumor suppressor	Downregulated	Not assessed	Is transcriptionally activated by p53 and inhibits cell growth by G0/G1 cell cycle arrest through inactivation of the MAPK/ERK pathway in DLBCL cells	Favorable	[^Citation41]
lincRNA-p21	Tumor suppressor	Downregulated	Not assessed	Regulates cell growth and cycle by functionally modulating downstream p21, cyclin D1 and CDK4	Favorable	[^Citation42]
SHG14	Oncogenic	Upregulated	miR-5590-3p	Promotes cell proliferation, migration, immune evasion and EMT	Not assessed	[^Citation43]
SHG16	Oncogenic	Upregulated	miR-497-5p	Promotes cell proliferation and cell cycle progression	Not assessed	[^Citation44]
TUG1	Oncogenic	Upregulated	MET	Inhibits the ubiquitination and degradation of MET oncoprotein and promotes cell proliferation and tumor growth	Not assessed	[^Citation45]
MALAT1	Oncogenic	Upregulated	miR-195	Enhances cell proliferation, migration and immune escape and EMT-like processes via Ras/ERK signaling and induces adriamycin resistance by triggering protective cell autophagy	Not assessed	[^Citation46,Citation48]
SMAD5-AS1	Tumor suppressor	Downregulated	miR-135b-5p	Inhibits tumor cell proliferation by inactivating the classic Wnt/β-catenin pathway	Not assessed	[^Citation47]
HULC	Oncogenic	Upregulated	Not assessed	Maintain cell survival and inhibit apoptosis	Not assessed	[^Citation52]

Note: “Not assessed” denotes that the direct targets or prognostic impacts of the lncRNAs were not assessed in the specific study.

Abbreviations: HOTAIR, HOX transcript antisense RNA; FIRRE, functional intergenic repeating RNA element; NEAT1_1, nuclear paraspeckle assembly transcript 1_1; PANDA, p21-associated ncRNA DNA damage activated; lincRNA-p21, long intergenic noncoding RNA-p21; SNHG14, small nucleolar RNA host gene 14; SNHG16, small nucleolar RNA host gene 16; TUG1, taurine-upregulated gene 1; MALAT1, metastasis-associated lung adenocarcinoma transcript 1; SMAD5-AS1, mothers against decapentaplegic homolog 5-antisense RNA 1; HULC, highly upregulated in liver cancer; EMT, epithelial-to-mesenchymal transition; H3K27me3, histone H3 trimethylation at lysine 27.

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