Potential Diagnostic, Prognostic and Therapeutic Targets of MicroRNAs in Human Gastric Cancer

Abstract

Human gastric cancer (GC) is characterized by a high incidence and mortality rate, largely because it is normally not identified until a relatively advanced stage owing to a lack of early diagnostic biomarkers. Gastroscopy with biopsy is the routine method for screening, and gastrectomy is the major therapeutic strategy for GC. However, in more than 30% of GC surgical patients, cancer has progressed too far for effective medical resection. Thus, useful biomarkers for early screening or detection of GC are essential for improving patients’ survival rate. MicroRNAs (miRNAs) play an important role in tumorigenesis. They contribute to gastric carcinogenesis by altering the expression of oncogenes and tumor suppressors. Because of their stability in tissues, serum/plasma and other body fluids, miRNAs have been suggested as novel tumor biomarkers with suitable clinical potential. Recently, aberrantly expressed miRNAs have been identified and tested for clinical application in the management of GC. Aberrant miRNA expression profiles determined with miRNA microarrays, quantitative reverse transcription-polymerase chain reaction and next-generation sequencing approaches could be used to establish sample specificity and to identify tumor type. Here, we provide an up-to-date summary of tissue-based GC-associated miRNAs, describing their involvement and that of their downstream targets in tumorigenic and biological processes. We examine correlations among significant clinical parameters and prognostic indicators, and discuss recurrence monitoring and therapeutic options in GC. We also review plasma/serum-based, GC-associated, circulating miRNAs and their clinical applications, focusing especially on early diagnosis. By providing insights into the mechanisms of miRNA-related tumor progression, this review will hopefully aid in the identification of novel potential therapeutic targets.

MicroRNA-144 functions as a tumor suppressor in gastric cancer by targeting cyclooxygenase-2

“…Furthermore, the dysregulation of miRNAs is reported to be involved in the pathogenic processes of GC tumorigenesis by regulating the expression of the miRNA's target genes. It has been revealed that the regulation of miRNAs participating in GC tumorigenesis is associated with cell proliferation and apoptosis-related genes (32). Therefore, numerous studies have suggested that miRNAs, including miR-10b, miR-106a and miR-107, may be used as biomarkers in GC (14,33,34).…”

Blockade of miR-663b inhibits cell proliferation and induces apoptosis in osteosarcoma via regulating TP73 expression

“…Evidences have indicated that miRNAs play critical roles in managing many normal biological processes, and abnormal expression of miRNAs is associated with various cancers occurrence, such as gas tric cancer, lung cancer, OS, etc. (12)(13)(14), and miRNAs serve as oncogenes or cancer suppressors during the progression of OS (15,16). For example, Bi et al (17) suggested that miR-100 serves as a cancer inhibitor in OS development via suppressing OS growth by regulating FGFR3 expression.…”

The significance of elevated plasma expression of microRNA 106b~25 clusters in gastric cancer

“…Since their discovery in 1993, emerging evidence showed that expression change of miRs is associated with cancer, involving GCs [14,15]. Because they are on intimate terms with tumor genesis, miRs have attracted great attention from researchers to search sensitive and specific biomarkers for early stage cancer.…”