Abstract
MicroRNAs (miRNAs) are small non-coding RNAs 18-25 nucleotides in length that downregulate gene expression during various crucial cell processes such as apoptosis, differentiation and development. Changes in the expression profiles of miRNAs have been observed in a variety of human tumors, including colorectal cancer (CRC). Functional studies indicate that miRNAs act as tumor suppressors and oncogenes. These findings significantly extend Vogelstein's model of CRC pathogenesis and have shown great potential for miRNAs as a novel class of therapeutic targets. Several investigations have also described the ability of miRNA expression profiles to predict prognosis and response to selected treatments in CRC patients, and support diagnosis of CRC among cancer of unknown primary site. miRNAs' occurrence has been repeatedly observed also in serum and plasma, and miRNAs as novel minimally invasive biomarkers have indicated reasonable sensitivity for CRC detection and compare favorably with the fecal occult blood test. In this review, we summarize the knowledge regarding miRNAs' functioning in CRC while emphasizing their significance in pathogenetic signaling pathways and their potential to serve as disease biomarkers and novel therapeutic targets.
Highlights
MicroRNAs comprise an abundant class of endogenous, small non-coding RNAs 18-25 nucleotides in length that repress protein translation through binding to target mRNAs
Findings that miRNAs play a role in cancer biology are further supported by the fact that more than 50% of miRNA genes are located at such chromosomal regions as fragile sites and regions of deletion or amplification that are altered in human cancer [8]
22 resected human tumors showed higher miR-21 expression than did the corresponding normal mucosa and decreased amounts of PDCD4 protein while mRNA levels were unchanged. These results argue for miR-21's having an important function in the pathogenesis of colorectal cancer (CRC), as it shows an inverse correlation with survival [35]
Summary
MicroRNAs (miRNAs) comprise an abundant class of endogenous, small non-coding RNAs 18-25 nucleotides in length that repress protein translation through binding to target mRNAs. When let-7 low-expressing DLD-1 colon cancer cells were transfected with let-7a-1 precursor, significant growth suppression with concurrent decrease of the KRAS protein levels was observed while the levels of both of their mRNAs remained almost unchanged [16] Another miRNA associated with KRAS regulation in CRC is miR-143 [17]. 22 resected human tumors showed higher miR-21 expression than did the corresponding normal mucosa and decreased amounts of PDCD4 protein while mRNA levels were unchanged These results argue for miR-21's having an important function in the pathogenesis of CRC, as it shows an inverse correlation with survival [35]. Identifying of colorectal cancer among adenocarcinoma of unknown primary site may improve prog-
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