Cell-free Circulating miRNA Biomarkers in Cancer

Abstract

Considerable attention and an enormous amount of resources have been dedicated to cancer biomarker discovery and validation. However, there are still a limited number of useful biomarkers available for clinical use. An ideal biomarker should be easily assayed with minimally invasive medical procedures but possess high sensitivity and specificity. Commonly used circulating biomarkers are proteins in serum, most of which require labor-intensive analysis hindered by low sensitivity in early tumor detection. Since the deregulation of microRNA (miRNA) is associated with cancer development and progression, profiling of circulating miRNAs has been used in a number of studies to identify novel minimally invasive miRNA biomarkers. In this review, we discuss the origin of the circulating cell-free miRNAs and their carriers in blood. We summarize the clinical use and function of potentially promising miRNA biomarkers in a variety of different cancers, along with their downstream target genes in tumor initiation and development. Additionally, we analyze some technical challenges in applying miRNA biomarkers to clinical practice.

Prospective evidence of a circulating microRNA signature as a non-invasive marker of hepatocellular carcinoma in HBV patients

“…In line with our findings, a recent study [19] showed that 3 serum miRNAs, including let-7f, could separate HBV-HCC cases from controls. MiR-122, the most abundant liver-specific miRNA, is considered a suppressor of cell proliferation and malignant transformation of hepatocytes with remarkable tumor inhibition activity [32][33][34]. Interestingly, although downregulation of miR-122 was frequently reported in the HCC tumor tissues [2,34,35], Qi et al [36] showed that miR-122 in serum was elevated in HCC patients and markedly reduced in post-operative serum samples, which is consistent with the observation in our study.…”

Circulating Epstein–Barr virus microRNAs miR‐BART7 and miR‐BART13 as biomarkers for nasopharyngeal carcinoma diagnosis and treatment

“…47 Hence, these highly expressed BART microRNAs may serve as another mechanistic biomarker for NPC recognition. A few studies have reported detection of BART microRNAs in sera or plasma from NPC patients, but only included small numbers of samples from NPC patients and lacked information on the source of these BART microRNAs (39)(40)(41). It is possible that some of the BART microRNAs detected in sera or plasma in these studies may also have come from apoptotic or circulating cancer cells.…”

miR-574-3p acts as a tumor promoter in osteosarcoma by targeting SMAD4 signaling pathway

“…SMAD4 overexpression could rescue the promoting effects of miR-574-3p on cancer cell growth, which additionally supports the theory that miR-574-3p may be associated with SMAD4. miRNAs are critical regulators and biomarkers for numerous types of cancers (8,(21)(22)(23)(24). There are several miRNAs that have been found to be abnormal in human osteosarcoma, including miR-141, miR-429, miR-451, miR-195, miR-183 miR-199a-3p, miR-127-3p and miR-376c (3,5,10,(25)(26)(27).…”

“…MicroRNA (miRNA) is a class of small non-coding RNA, with lengths of 18-22 nucleotides; they play important roles in numerous biological processes through transcriptional suppression of target genes (6)(7)(8). The critical functions of numerous miRNAs in cancer biology have been illustrated, including the regulation of various cellular processes, such as proliferation and apoptosis (3,5,9,10).…”