miRNA-guided reprogramming of glucose and glutamine metabolism and its impact on cell adhesion/migration during solid tumor progression

Abstract

MicroRNAs (miRNAs) are small, non-coding RNAs about 22 nucleotides in length that regulate the expression of target genes post-transcriptionally, and are highly involved in cancer progression. They are able to impact a variety of cell processes such as proliferation, apoptosis and differentiation and can consequently control tumor initiation, tumor progression and metastasis formation. miRNAs can regulate, at the same time, metabolic gene expression which, in turn, influences relevant traits of malignancy such as cell adhesion, migration and invasion. Since the interaction between metabolism and adhesion or cell movement has not, to date, been well understood, in this review, we will specifically focus on miRNA alterations that can interfere with some metabolic processes leading to the modulation of cancer cell movement. In addition, we will analyze the signaling pathways connecting metabolism and adhesion/migration, alterations that often affect cancer cell dissemination and metastasis formation.

Potential of the miR-200 Family as a Target for Developing Anti-Cancer Therapeutics

“…MicroRNAs (miRNAs/miRs) are noncoding single-stranded RNAs of 18–24 nucleotides in length. They can modulate gene expression through post-transcriptional control and are involved in cancer cell proliferation [ 1 , 2 ], apoptosis [ 3 , 4 ], invasion [ 5 , 6 ], metastasis [ 7 ], and anti-cancer drug resistance [ 8 ].…”

Metabolic reprogramming by miRNAs in the tumor microenvironment: Focused on immunometabolism

“…Co-regulation of glycolysis and flux to the PPP is critical for tumorigenesis and/or malignancy. The conversion of G6P into PPP, in particular, enhances cancer aggressiveness by producing ribose 5-phosphate and reducing equivalents such as NADPH, which is used in lipogenesis and also mitigation of oxidative stress ( 134 ). In lung tumors, miR-1 and miR-206 mediate the increase in G6P and subsequent decrease in nuclear factor erythroid-related factor 2 (NRF2) function ( 135 ).…”

“…Many cancer cells and TME-related compounds, including miRNAs, modulate glutamine absorption and metabolism. The oncosuppressor miR-137 targets alanine, serine, cysteine, and glutamate transporter (ASCT2), negatively correlated with ASCT2 in pancreatic ductal adenocarcinoma, pancreatic cancer, glioblastoma, and CRC ( 134 ). Epigenetic downregulation of miR-137 results in increased glutamine uptake, allowing tumor cells to grow in an unfavorable microenvironment due to abundant glutamine availability ( 172 ).…”

Cancer Cell Metabolism Reprogramming and Its Potential Implications on Therapy in Squamous Cell Carcinoma of the Head and Neck: A Review

“…Glutamine can also act as a nitrogen donor for the synthesis of purine and pyrimidine nucleotides, amino acids, and other metabolites. Finally, glutamine catabolism results in the production of lactate, alanine, and ammonia, thus maintaining non-essential amino acid pools [ 12 , 13 , 14 , 15 , 16 ]. An increased production of NADPH is essential for the biosynthesis of fatty acids and serves as the ultimate donor of reductive power for detoxifying the cell from the enormous amount of reactive oxygen species (ROS) that accumulate as a result of the high proliferation rate.…”