miR-186 Regulates Glycolysis through Glut1 During the Formation of Cancer-associated Fibroblasts

Abstract

Emerging evidence has suggested that glycolysis is enhanced in cancer-associated fibroblasts (CAF), and miR-186 is downregulated during the CAF formation. However, it is not clear whether miR-186 is involved in the regulation of glycolysis and what the role of miR-186 plays during the CAF formation. In this study, quantitative PCR analysises show miR-186 is downregulated during the CAF formation. Moreover, miR-186 targets the 3' UTR of Glut1, and its overexpression results in the degradation of Glut1 mRNA, which eventually reduces the level of Glut1 protein. On the other hand, knockdown of miR-186 increased the expression of Glut1. Both time course and dose response experiments also demonstrated that the protein and mRNA levels of Glut1 increase during CAF formation, according to Western blot and quantitative PCR analyses, respectively. Most importantly, besides the regulation on cell cycle progression, miR-186 regulates glucose uptake and lactate production which is mediated by Glut1. These observations suggest that miR-186 plays important roles in glycolysis regulation as well as cell cycle checkpoint activation.

MicroRNA-186 regulates the invasion and metastasis of bladder cancer via vascular endothelial growth factor C

“…Zhang et al (13) revealed that miR-186 may be a diagnostic and predictive factor for pancreatic ductal adenocarcinoma, and it affects the proliferation and invasion of tumor cells (13). Lee et al (12) demonstrated that upregulated miR-186 is associated with the proliferation of human lung fibroblasts and Sun et al (11) indicated that miR-186 regulates the formation of tumor-related fibroblasts. In addition, Cui et al (10) revealed that miR-186 inhibits the proliferation and metastasis of non-small-cell lung carcinoma cells by targeting Rock1.…”

“…miR-186 is one of the most studied miRNA molecules, and it regulates the apoptosis, proliferation and autophagy of various types of tumors (10)(11)(12)(13). However, few reports have been published regarding the effect and mechanism of action of miR-186 on bladder cancer (14,15).…”

Impaired Replication Timing Promotes Tissue-Specific Expression of Common Fragile Sites

“…The Genome Data Viewer NCBI database (build 37) locates 52 different genes along the fragile region ( Figure S1), with many of these genes regulating important cellular functions; a long non-coding RNA is also present (LINC01360), as well as a microRNA (miR186) known to function as a tumor suppressor in several solid tumors [33]. An 886 kb long gene, NEGR1 (neuronal growth regulator 1) is also present in the region, underscoring the previously reported association between long genes and CFSs instability [34].…”

Genetic alterations and epigenetic alterations of cancer-associated fibroblasts

“…miR-186 in CAFs is involved in glycolysis, and combined with the 3′-untranslated region of its target gene glucose transporter 1 (Glut 1), it is active in regulating the uptake of glucose and production of lactate (106). The roles of CAFs in cancer glucose and energy metabolism are recognized using a novel method named the ‘reverse Warburg effect’ (23,107,108).…”