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Review
. 2020 Feb 10;16(7):1194-1206.
doi: 10.7150/ijbs.40769. eCollection 2020.

LncRNAs regulate metabolism in cancer

Wenyu Lin  1 , Qiyin Zhou  2 , Chao-Qun Wang  3 , Liyuan Zhu  1 , Chao Bi  4 , Shuzhen Zhang  5 , Xian Wang  2 , Hongchuan Jin  1
Affiliations
Review

LncRNAs regulate metabolism in cancer

Wenyu Lin et al. Int J Biol Sci. .

Abstract

Metabolic reprogramming is a hallmark of cancer. Mammalian genome is characterized by pervasive transcription, generating abundant non-coding RNAs (ncRNAs). Long non-coding RNAs (lncRNAs) are freshly discovered functional ncRNAs exerting extensive regulatory impact through diverse mechanisms. Emerging studies have revealed widespread roles of lncRNAs in the regulation of various cellular activities, including metabolic pathways. In this review, we summarize the latest advances regarding the regulatory roles of lncRNAs in cancer metabolism, particularly their roles in mitochondrial function, glucose, glutamine, and lipid metabolism. Moreover, we discuss the clinical application and challenges of targeting lncRNAs in cancer metabolism. Understanding the complex and special behavior of lncRNAs will allow a better depiction of cancer metabolic networks and permit the development of lncRNA-based clinical therapies by targeting cancer metabolism.

Keywords: Cancer; Long non-coding RNA; Metabolism.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

Figures

Figure 1
Figure 1
LncRNAs regulate mitochondria function. (A, B) LncRNA MDRL (A) and MPRL (B) act as sponges of miR-484 and miR-483-5p, respectively, which targets Fis1 to inhibit its expression and regulate mitochondrial dynamics. (C) HOTAIR knockdown impairs mitochondrial function via reducing its OXPHOS components including UQCRQ and triggers ROS stress. Also, HOTAIR blockage activates MICU and induces apoptosis by reducing Bcl-2 and increasing caspase 3 and BAX. (D) Mitochondrial part of SAMMSON inhibits mitochondrial membrane potential depolarization, mPOS and tumor apoptosis by interacting with p32 and enhancing its function. (E) Nuclear encoded RMRP transports into mitochondria facilitated by HuR and GRSF1 to induce mtDNA replication and increase OXPHOS subunit, thus promoting mitochondrial respiration. (F) Tug1 interacts with tug1-binding element upstream of PGC-1α promoter to maintain complex I and III activity and increase mitochondrial bioenergetics. (G) SNHG3 sponges miRNA-186-5p and interacts with EIF4AIII to regulate gene expression related to TCA cycle and OXPHOS activity such as PDHB, IDH2 and UQCRH.
Figure 2
Figure 2
LncRNAs regulate cancer metabolism. By regulating glycolysis, glutaminolysis, and lipid metabolism, lncRNAs can reprogram major cancer metabolism pathways. Detailed mechanisms of action of these lncRNAs are described in the text.
Figure 3
Figure 3
Regulation of cancer-associated fibroblasts by lncRNAs. (A) CXCL14 secreted by CAFs upregulates LINC00092, which binds to PFKFB2 to activate PFK-1 via PFKFB2 catalytic product F-2, 6-BP and then promotes glycolysis. LINC00092 also maintains CAFs-like phenotype and mediates cancer metastasis. (B) CXCL14 secreted by GASCs elevates lncRNA UCA1 expression, then sponges miR-182 to activate PFKFB2. (C) LncRNA-CAF is synthesized in stromal fibroblasts or imported from tumor cell-excreted exosomes to upregulate IL-33, which promotes tumor cell metastasis, mediates CAFs transformation, inhibits CAFs autophagy and induces angiogenesis. (D) Upon lactate stimulation, TAMs synthesize and secret lncRNA HISLA wrapped in vesicles, which are then internalized by cancer cells and abolish HIF-1α degradation by competitively binding to PHD2, consequently promotes glycolysis and chemoresistance.
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