Abstract
Metabolism reprogramming is one of the hallmarks of cancer cells, especially glucose metabolism, to promote their proliferation, metastasis and drug resistance. Cancer cells tend to depend on glycolysis for glucose utilization rather than oxidative phosphorylation, which is called the Warburg effect. Genome instability of oncogenes and tumor-inhibiting factors is the culprits for this anomalous glycolytic fueling, which results in dysregulating metabolism-related enzymes and metabolic signaling pathways. It has been extensively demonstrated that protein-coding genes are involved in this process; therefore, glycolysis-targeted therapy has been widely used in anti-tumor combined therapy via small molecular inhibitors of key enzymes and regulatory molecular. The long non-coding RNA, which is a large class of regulatory RNA with longer than 200 nucleotides, is the novel and significant regulator of various biological processes, including metabolic reprogramming. RNA interference and synthetic antisense oligonucleotide for RNA reduction have developed rapidly these years, which presents potent anti-tumor effects both in vitro and in vivo. However, lncRNA-based glycolysis-targeted cancer therapy, as the highly specific and less toxic approach, is still under the preclinical phase. In this review, we highlight the role of lncRNA in glucose metabolism and dissect the feasibility and limitations of this clinical development, which may provide potential targets for cancer therapy.
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Data availability
The data of clinical trials was from https://clinicaltrials.gov/.
Abbreviations
- AGPG:
-
Actin gamma 1 pseudogene
- AML:
-
Acute myeloid leukemia
- AMPK:
-
AMP-activated protein kinase
- ANXA2P2:
-
Annexin A2 Pseudogene 2
- ASO:
-
Antisense oligonucleotide
- CHC:
-
α-Cyano-4-hydroxycinnamic acid
- CRC:
-
Colorectal cancer
- ceRNA:
-
Competing endogenous RNA
- CR:
-
Complete remission
- DANCE:
-
Differentiation antagonizing non-coding RNA
- DNMT1:
-
DNA methyltransferase 1
- E2F1:
-
E2F transcription factor 1
- ELF3-AS1:
-
E74 like ETS transcription factor 3 antisense 1
- EGF:
-
Epidermal growth factor
- EC:
-
Esophageal cancer
- EV:
-
Extracellular vesicle
- FCS:
-
Familial chylomicronemia syndrome
- FGFR1:
-
Fibroblast growth factor receptor type1
- FDA:
-
Food and Drug Administration
- FILNC1:
-
FoxO-induced long non-coding RNA 1
- F-1,6-BP:
-
Fructose-1,6-biphosphate
- FBPase:
-
Fructose-2,6-biphosphatase
- F-6-P:
-
Fructose-6-phosphate
- GBS:
-
Gallbladder cancer
- GLUTs:
-
Glucose transports
- G-6-P:
-
Glucose-6-phosphate
- GSH/GSSH:
-
Glutathione/oxidized glutathione
- GADPH:
-
Glyceraldehyde-3-phosphate dehydrogenase
- GLCC1:
-
Glycolysis-associated lncRNA of colorectal cancer
- GPNMB:
-
Glycoprotein NMB
- HCC:
-
Hepatocellular carcinoma
- hnRNP A1:
-
Heterogeneous nuclear ribonucleoprotein A1
- HK:
-
Hexokinase
- HDAC2:
-
Histone deacetylase
- HER:
-
Hypoxia reaction elements
- HIF-1α:
-
Hypoxia-inducible factor 1α
- IGF2BP2:
-
Insulin-like growth factor 2 mRNA-binding protein 2
- IDH:
-
Isocitrate dehydrogenase
- LDH:
-
Lactate dehydrogenase
- LNA:
-
Locked nuclear acid
- LncRNA:
-
Long non-coding RNA
- mTOR:
-
Mammalian target of rapamycin
- MALAT1:
-
Metastasis-associated lung adenocarcinoma transcript 1
- MCT:
-
Monocarboxylate transport family
- MM:
-
Multiple myeloma
- NBR2:
-
Neighbor of BRCA1 gene 2
- NcRNAs:
-
Non-coding RNAs
- NSCLC:
-
Non-small cell lung cancer
- OSCC:
-
Oral squamous cell carcinoma
- OXPHOS:
-
Oxidative phosphorylation
- TIGAR:
-
P53-induced glycolysis and apoptosis regulator
- PFK-1:
-
6-Phosphofructokinase-1
- PFK-2/PFKFB:
-
6-Phosphofructokinase-2/fructose-2,6-biphosphatase
- PPP:
-
Pentose phosphate pathway
- PI3K:
-
Phosphatidylinositol-3-hydroxykinase
- PEP:
-
Phosphoenolpyruvate
- PVT1:
-
Plasmacytoma variant translocation
- PET:
-
Positron emission tomography scans
- PHD:
-
Proline hydroxylase domain
- PDH:
-
Pyruvate dehydrogenase
- PDK:
-
Pyruvate dehydrogenase kinase
- PK:
-
Pyruvate kinase
- PPARA:
-
Peroxisome proliferator-activated receptor alpha
- ROS:
-
Reactive oxygen species
- RCC:
-
Renal cell carcinoma
- RNAi:
-
RNA interference
- RRM2:
-
M2 subunit of ribonucleotide reductase
- SIRT1:
-
Deacetylases Sirtuin
- siRNA:
-
Small interference RNA
- SGLT:
-
Sodium-dependent glucose transporter family
- SCO2:
-
Synthesis of cytochrome c oxidase 2
- SOX:
-
Cytochrome c oxidase complex
- TF:
-
Transcriptional factors
- TCA:
-
Tricarboxylic acid
- TNBC:
-
Triple-negative breast cancer
- TSC1 and TSC2:
-
Tuberous sclerosis 1,2
- ME:
-
Tumor microenvironment
- TAM:
-
Tumor-associated macrophages
- VHL:
-
Von Hipple-Lindau protein
- XIST:
-
X-inactive specific transcript
- 18F-FDG:
-
18F-labeled 2-fluoro-2-deoxy-d-glucose
- 2-DG:
-
2-Deoxyglucose
- 3-BrPA:
-
3-Bromopyruvate
- α-DG:
-
α-Hydroxyglutarate
- α-KG:
-
α-Ketoglutarate
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All authors contributed to the study conception and design. RL performed the literature search and analysis. RL prepared tables and figures, and drafted the manuscript. AH, YS and XW revised the manuscript.
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Liu, R., Wang, X., Shen, Y. et al. Long non-coding RNA-based glycolysis-targeted cancer therapy: feasibility, progression and limitations. Mol Biol Rep 48, 2713–2727 (2021). https://doi.org/10.1007/s11033-021-06247-7
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DOI: https://doi.org/10.1007/s11033-021-06247-7