Regulatory Mechanisms of LncRNAs in Cancer Glycolysis: Facts and Perspectives
TL;DR: In this paper, the authors highlight regulatory mechanisms for lncRNAs in aerobic glycolysis that provide novel insights into cancer development and provide new strategies for clinical cancer management.
Abstract: Cancer cells exhibit distinct metabolic characteristics that employ glycolysis to provide energy and intermediary metabolites. This aberrant metabolic phenotype favors cancer progression. LncRNAs are transcripts longer than 200 nucleotides that do not encode proteins. LncRNAs contribute to cancer progression and therapeutic resistance and affect aerobic glycolysis via multiple mechanisms, including modulating glycolytic transporters and enzymes. Further, dysregulated signaling pathways are vital for glycolysis. In this review, we highlight regulatory mechanisms for lncRNAs in aerobic glycolysis that provide novel insights into cancer development. Moreover, a comprehensive understanding of the regulatory mechanisms of lncRNAs in aerobic glycolysis can provide new strategies for clinical cancer management.
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TL;DR: In this article, a nanoprodrug formed by a F127-coated drug dimer was used to inhibit glycolysis of cancer cells and alleviate the immunosuppressive microenvironment.
Abstract: Blocking energy metabolism of cancer cells and simultaneously stimulating the immune system to perform immune attack are significant for cancer treatment. However, how to potently deliver different drugs with these functions remains a challenge. Herein, we synthesized a nanoprodrug formed by a F127-coated drug dimer to inhibit glycolysis of cancer cells and alleviate the immunosuppressive microenvironment. The dimer was delicately constructed to connect lonidamine (LND) and NLG919 by a disulfide bond which can be cleaved by excess GSH to release two drugs. LND can decrease the expression of hexokinase II and destroy mitochondria to restrain glycolysis for energy supply. NLG919 can reduce the accumulation of kynurenine and the number of regulatory T cells, thus alleviating the immunosuppressive microenvironment. Notably, the consumption of GSH by disulfide bond increased the intracellular oxidative stress and triggered immunogenic cell death of cancer cells. This strategy can offer more possibilities to explore dimeric prodrugs for synergistic cancer therapy.
55 citations
TL;DR: Understanding the relationship between lncRNA expression and ER stress could open new avenues, and suggest potential therapies to treat various types of cancer.
Abstract: Cancer cells must overcome a variety of external and internal stresses to survive and proliferate. These unfavorable conditions include the accumulation of mutations, nutrient deficiency, oxidative stress, and hypoxia. These stresses can cause aggregation of misfolded proteins inside the endoplasmic reticulum. Under these conditions, the cell undergoes endoplasmic reticulum stress (ER‐stress), and consequently initiates the unfolded protein response (UPR). Activation of the UPR triggers transcription factors and regulatory factors, including long noncoding RNAs (lncRNAs), which control the gene expression profile to maintain cellular stability and hemostasis. Recent investigations have shown that cancer cells can ensure their survival under adverse conditions by the UPR affecting the expression of lncRNAs. Therefore, understanding the relationship between lncRNA expression and ER stress could open new avenues, and suggest potential therapies to treat various types of cancer.
6 citations
TL;DR: Three key glycolysis-associated lncRNAs constituting a signature could predict the risk levels in BC, provide a reference for stratification, and be used as prognostic markers for BC diagnosis and treatment.
4 citations
TL;DR: The role of MAFG-AS1 in cancer progression, competing endogenous RNA (ceRNA) activity, regulation of EMT, glycolysis, energy metabolism, transcription factors, proteasomal degradation, and signaling pathways is discussed in this article .
Abstract: Long non-coding RNAs (lncRNAs) have more than 200 nucleotides and do not encode proteins. At the same time, they can regulate various biological functions and therefore play an essential role as oncogenes or tumor suppressors in human cancers. MAFG-AS1 is an antisense RNA of MAF BZIP Transcription Factor G (MAFG) located at chromosome 17q25.3 head-to-head with the MAFG encoding gene containing a transcript size of 1895 bp. Accumulating evidence shows that MAFG-AS1 is overexpressed in many cancers, functions as an oncogene, and is significantly associated with poor clinical characteristics and prognosis. In this review, we first discuss the recent literature regarding the role of MAFG-AS1 in different cancers as well as its diagnostic and prognostic values. Then we will provide insights into its biological functions, such as its role in cancer progression, competing endogenous RNA (ceRNA) activity, regulation of EMT, glycolysis, energy metabolism, transcription factors, proteasomal degradation, and signaling pathways.
3 citations
TL;DR: An in-depth understanding is provided of the role of differentially expressed lncRNAs in the key signal pathways of glucose metabolism, which may help to provide new therapeutic targets and new diagnostic and prognostic markers for human cancer.
Abstract: In response to overstimulation of growth factor signaling, tumor cells can reprogram their metabolism to preferentially utilize and metabolize glucose to lactate even in the presence of abundant oxygen, which is termed the “Warburg effect” or aerobic glycolysis. Long noncoding RNAs (lncRNAs) are a group of transcripts longer than 200 nucleotides and do not encode proteins. Accumulating evidence suggests that lncRNAs can affect aerobic glycolysis through multiple mechanisms, including the regulation of glycolytic transporters and key rate-limiting enzymes. In addition, maladjusted signaling pathways are critical for glycolysis. Therefore, this article mainly reviews the lncRNAs involved in the regulation of tumor glycolysis key signal pathways in recent years and provides an in-depth understanding of the role of differentially expressed lncRNAs in the key signal pathways of glucose metabolism, which may help to provide new therapeutic targets and new diagnostic and prognostic markers for human cancer.
1 citations
References
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TL;DR: Recognition of the widespread applicability of these concepts will increasingly affect the development of new means to treat human cancer.
51,099 citations
TL;DR: Although they escaped notice until relatively recently, miRNAs comprise one of the more abundant classes of gene regulatory molecules in multicellular organisms and likely influence the output of many protein-coding genes.
32,946 citations
TL;DR: It is proposed that the metabolism of cancer cells, and indeed all proliferating cells, is adapted to facilitate the uptake and incorporation of nutrients into the biomass needed to produce a new cell.
Abstract: In contrast to normal differentiated cells, which rely primarily on mitochondrial oxidative phosphorylation to generate the energy needed for cellular processes, most cancer cells instead rely on aerobic glycolysis, a phenomenon termed “the Warburg effect.” Aerobic glycolysis is an inefficient way to generate adenosine 5′-triphosphate (ATP), however, and the advantage it confers to cancer cells has been unclear. Here we propose that the metabolism of cancer cells, and indeed all proliferating cells, is adapted to facilitate the uptake and incorporation of nutrients into the biomass (e.g., nucleotides, amino acids, and lipids) needed to produce a new cell. Supporting this idea are recent studies showing that (i) several signaling pathways implicated in cell proliferation also regulate metabolic pathways that incorporate nutrients into biomass; and that (ii) certain cancer-associated mutations enable cancer cells to acquire and metabolize nutrients in a manner conducive to proliferation rather than efficient ATP production. A better understanding of the mechanistic links between cellular metabolism and growth control may ultimately lead to better treatments for human cancer.
12,380 citations
10,654 citations
TL;DR: In this article, the authors propose that persistent metabolism of glucose to lactate even in aerobic conditions is an adaptation to intermittent hypoxia in pre-malignant lesions, which leads to microenvironmental acidosis requiring evolution to phenotypes resistant to acid-induced cell toxicity.
Abstract: If carcinogenesis occurs by somatic evolution, then common components of the cancer phenotype result from active selection and must, therefore, confer a significant growth advantage. A near-universal property of primary and metastatic cancers is upregulation of glycolysis, resulting in increased glucose consumption, which can be observed with clinical tumour imaging. We propose that persistent metabolism of glucose to lactate even in aerobic conditions is an adaptation to intermittent hypoxia in pre-malignant lesions. However, upregulation of glycolysis leads to microenvironmental acidosis requiring evolution to phenotypes resistant to acid-induced cell toxicity. Subsequent cell populations with upregulated glycolysis and acid resistance have a powerful growth advantage, which promotes unconstrained proliferation and invasion.
4,361 citations