Downregulation of exosome‐encapsulated miR‐548c‐5p is associated with poor prognosis in colorectal cancer

Abstract

The role of circulating exosomal microRNAs (miRNAs) in colorectal cancer (CRC) has drawn more and more attention during the past few years. Previously, we have identified several specific miRNAs in serum exosomes as potential CRC biomarkers. However, little is known about the association between exosome-encapsulated miR-548c-5p and outcomes of patients with CRC. In the current study, the expression of serum exosomal miR-548c-5p was investigated by quantitative real-time polymerase chain reaction. Its correlation with CRC prognosis was estimated by Kaplan-Meier survival and log-rank tests. Cox regression analysis based on uni- and multivariate analyses was performed to estimate the relationship of exosome-encapsulated miR-548c-5p with the clinicopathological factors of patients with CRC. Reduced levels of serum exosomal miR-548c-5p were more significant in CRC patients with liver metastasis and at later TNM stage (III/IV tumor stages). Serum exosomal miR-548c-5p could inhibit the proliferation of CRC cells, while the precise molecular mechanisms warranted further elucidation. In addition, decreased levels of serum exosomal miR-548c-5p were independently associated with shorter overall survival in CRC adjusted by age, sex, tumor grade vascular infiltration, TNM stage (III/IV tumor stages) and metastasis (hazard ratio = 3.40, 95% confidence interval 1.02-11.27; P = 0.046). The downregulation of exosomal miR-548c-5p in serum predicts poor prognosis in patients with CRC. Exosomal miR-548c-5p may be a critical biomarker for CRC diagnosis and prognosis.

Circulating Extracellular Vesicle MicroRNA as Diagnostic Biomarkers in Early Colorectal Cancer—A Review

“…Liu et al likewise found elevated miR-486 levels in the serum EVs of CRC patients of all stages [74]. Downregulation of serum EV miR-548c was also reported by Peng and colleagues in 108 CRC patients (including 25 stage I and 21 stage II patients) and was associated with shorter survival and liver metastases [82]. However, in this study, miR-548c was demonstrated to have a 1.59-fold decrease and miR-486 was shown to have a 1.61-fold increase.…”

“…This has possible efficiency benefits over a method such as UC, with potential of ease of scalability and automation. Other methods of EV isolation include precipitation and filtration that were also in a number of studies [74,[80][81][82]118]. Differences in EV isolation methods, including UC, precipitation, and SEC, have demonstrated significant variance in the properties of the isolated vesicles, the total miRNA yield, as well as the EV-specific miRNA levels when analysing the same samples [119,120].…”

The Impact of miRNA in Colorectal Cancer Progression and Its Liver Metastases<strong> </strong>

“…Moreover, recent evidence has suggested that liver pre-metastatic niche could be promoted by exosomal miR-21 of CRC cells, through the miR-21-TLR7-IL6 axis [116]. Significantly increased levels of serum exosomal miR-6803-5p [117] and decreased levels of miR-548c-5p have been recently associated with poor survival and liver metastasis of CRC patients [118]. However, the molecular mechanisms by which both miR-6803-5p and miR-548c-5p influence CRC metastasis remain largely unknown.…”

Untitled

“…miRNAs contribute to both stem cell homeostasis in normal development and to cell fate decisions in CRC [13]. Clinical studies have also confirmed their utility as molecular diagnostic and prognostic biomarkers for a wide range of human diseases, including CRC [14][15][16]. Some evidences suggest that age, gender and other parameters could affect miRNA expression.…”