Abstract
The gastrointestinal (GI) tract in mammals is comprised of dozens of cell types with varied functions, structures, and histological locations that respond in a myriad of ways to epigenetic and genetic factors, environmental cues, diet, and microbiota. The homeostatic functioning of these cells contained within this complex organ system has been shown to be highly regulated by the effect of microRNAs (miRNA). Multiple efforts have uncovered that these miRNAs are often tightly influential in either the suppression or overexpression of inflammatory, apoptotic, and differentiation-related genes and proteins in a variety of cell types in colorectal cancer (CRC). The early detection of CRC and other GI cancers can be difficult, attributable to the invasive nature of prophylactic colonoscopies. Additionally, the levels of miRNAs associated with CRC in biofluids can be contradictory and, therefore, must be considered in the context of other inhibiting competitive endogenous RNAs (ceRNA) such as lncRNAs and circRNAs. There is now a high demand for disease treatments and noninvasive screenings such as testing for bloodborne or fecal miRNAs and their inhibitors/targets. The breadth of this review encompasses current literature on well-established CRC-related miRNAs and the possibilities for their use as biomarkers in the diagnoses of this potentially fatal GI cancer.
Highlights
Academic Editors: AlessandroAs a generalized class of biomolecules, RNA species occupy a unique niche that can alternate between being transient and/or enduring, while being consequential or seemingly neutral to cellular homeostasis, growth, and survival across a myriad of taxonomic levels of life
Levels of miR-18a were found to be elevated in the serum of colorectal cancer (CRC) patients and, are a potential biomarker [69], while the application of isolated miR-18a inhibits CRC cell growth through the indirect regulation of the PI3K/AKT pathway [149] and has the potential to be sponged by the tumor-suppressing long noncoding RNA (lncRNA) CASC2 [150]
Methodologies for the building of unique miRNA sponges with multiple seed target sites were quickly introduced [309]. These sponges have been able to isolate oncogenic miRNAs such as that observed with miR-21 sponging in renal cancer [310], gastric cancer [311], glioblastomas [312], and esophageal carcinomas [313]
Summary
As a generalized class of biomolecules, RNA species occupy a unique niche that can alternate between being transient and/or enduring, while being consequential or seemingly neutral to cellular homeostasis, growth, and survival across a myriad of taxonomic levels of life. Levels of miR-18a were found to be elevated in the serum of CRC patients and, are a potential biomarker [69], while the application of isolated miR-18a inhibits CRC cell growth through the indirect regulation of the PI3K/AKT pathway [149] and has the potential to be sponged by the tumor-suppressing lncRNA CASC2 [150]. The miR-135 family was originally tagged as an oncogene by its targeting and downregulating of the tumor suppressor APC (with which miR-135b it has a reciprocally inhibitory relationship [240]) in CRC, which regulates the Wnt/ß-catenin pathway [241,242] as well as priming pancreatic cancer cells for pro-carcinogenic metabolic conditions through PFK1 downregulation [243]. Decreases [64,113–115], yet again stressing the need for the analysis of miRNA levels within a context of known targets and other ncRNA inhibitors In this regard, the growth-suppressing consequences of miR-150 expression in CRC can be arrested by means of sponging via the lncRNAs ZFAS1 [286] and PART1 [287]. Being able to couple known miR-195 targets and sponges, with stably reduced miR-195 in CRC tissues insinuates that miR-195 is a ripe area of further research in CRC
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