Non-Coding RNAs Operate in the Crosstalk Between Cancer Metabolic Reprogramming and Metastasis

Abstract

Metastasis, the spread of cancer cells from a primary tumor to a secondary site, represents one of the hallmarks of malignancies and the leading cause of cancer-related death. The process of metastasis is a result of the interaction of genetic heterogeneity, abnormal metabolism, and tumor microenvironments. On the other hand, metabolic reprogramming, another malignancy hallmark, refers to the ability of cancer cells to alter metabolic and nutrient acquisition modes in order to support the energy demands for accomplishing the rapid growth, dissemination, and colonization. Cancer cells remodel metabolic patterns to supplement nutrients for their metastasis and also undergo metabolic adjustments at different stages of metastasis. Genes and signaling pathways involved in tumor metabolic reprogramming crosstalk with those participating in metastasis. Non-coding RNAs are a group of RNA molecules that do not code proteins but have pivotal biological functions. Some of microRNAs and lncRNAs, which are the two most extensively studied non-coding RNAs, have been identified to participate in regulating metabolic remodeling of glucose, lipid, glutamine, oxidative phosphorylation, and mitochondrial respiration, as well as the process of metastasis involving cell motility, transit in the circulation and growth at a new site. This article reviews recent progress on non-coding RNAs operating in the crosstalk between tumor metabolic reprogramming and metastasis, particularly those influencing metastasis through regulating metabolism, and the underlying mechanisms of how they exert their regulatory functions.

Mechanisms of Metabolic Reprogramming in Cancer Cells Supporting Enhanced Growth and Proliferation

“…As ncRNAs were initially considered to lack biological function because they do not encode proteins, they play a role in cancer progression by regulating enzymes and pathways involved in the metabolic reprogramming of cancer cells. This regulation primarily occurs through glucose, glutamine, and lipid metabolism and involves two types of ncRNA, long-chain non-coding RNA (lncRNA) and microRNA (miRNA) [ 154 ].…”

“…There are several enzymes related to glucose metabolism that are regulated by ncRNAs in cancer. HK2 expression, for example, is downregulated by miR-199a-5p and miR-125b, with lower expression of these ncRNAs corresponding with enhanced growth [ 154 ]. In breast cancer, GLUT1 and PK expression are downregulated by the secretion of vesicles containing miR-122, which decreases glucose uptake in non-tumor cells to increase nutrient availability in pre-metastatic cells and promote metastasis [ 156 ].…”

“…For example, miR-149-5p, activated by circulating endogenous RNA circNRIP1, stimulates the PI3K/Akt/mTOR pathway to promote cancer cell growth. The PI3K/Akt/mTOR pathway can also be activated by LINC00963 via PGK1 ubiquitination blockage and by miR-384 via upregulation of pleiotrophin and lipogenic genes [ 154 ]. The variety of ncRNAs that affect metabolic processes and upstream oncogenic signaling pathways demonstrates the growing importance of ncRNAs in the field.…”

Current Understanding of the HIF-1-Dependent Metabolism in Oral Squamous Cell Carcinoma

“…Short 18–22 base pair long endogenous miRNAs play a key role in controlling gene expression by regulating several physiological, but also pathological processes, including carcinogenesis [ 81 ]. In addition, miRNAs have been identified as participating in the regulation of metabolic remodulating [ 82 ]. In this context, a number of hypoxia and HIF-dependent miRNAs with oncogenic and/or suppressive functions in cancer development were summarized [ 80 , 83 , 84 , 85 ].…”

The Novel Non-coding Transcriptional Regulator Gm18840 Drives Cardiomyocyte Apoptosis in Myocardial Infarction Post Ischemia/Reperfusion

“…Emerging evidence has demonstrated that long non-coding RNAs (lncRNAs) display diverse cellular functions and widely participate in both physiological and pathophysiological processes ( Li and Sun, 2020 ; Sayad et al, 2020 ; Zhang et al, 2020 ). LncRNAs are a diverse class of RNA transcripts longer than 200 nucleotides that have limited protein coding capacity ( Zhou et al, 2020 ).…”