Current perspectives toward the identification of key players in gastric cancer microRNA dysregulation

Abstract

Acquired genetic and epigenetic alterations in normal cells give rise to transformed cells, which lead to tumor development. Elucidation of the precise mechanisms underlying primary and metastatic tumor formation is required. MicroRNAs (miRNAs) are small noncoding RNAs that play a major role in post-transcriptional gene regulation during various biological processes. Accumulating evidence suggests that dysregulation of miRNAs is intimately involved in the carcinogenesis, progression and metastasis of many cancers, including gastric cancers (GCs), while the alteration of certain miRNAs provides biomarkers to detect early GCs. This review summarizes the most recent findings into the mechanisms of miRNA-mediated regulation of GCs, which will support the development of diagnostic biomarkers and novel therapeutic strategies.Gastric cancer (GC) is the fifth most prevalent type of malignancy and the third leading cause of cancer-related death worldwide. 1 The major histological type of GC is gastric adenocarcinoma, which can be further divided into intestinal and diffuse types according to the Lauren classification. 2 Although most GCs are sporadic and caused by infection, such as those caused by Helicobacter pylori bacteria or Epstein-Barr virus (EBV), a small number of GC cases are associated with heritable mutations in particular genes, including E-cadherin (CDH1) or mismatch repair genes (Lynch syndrome). 3,4 Despite recent advances in diagnostic modalities, such as computed tomographic scanning, endoscopic screening and the development of molecular-targeted drugs, the median overall survival of patients with advanced GC is still 11.3-13.8 months, according to recent Phase 3 trials. 5-7 Therefore, understanding the precise molecular mechanisms underlying GC progression is crucial for the development of novel therapeutic strategies for patients with GC.

Interaction between inflammatory mediators and miRNAs in Helicobacter pylori infection

“…Overall, our results showed that miRNAs miR-103, miR-181c, miR-370 and miR-375 are down-regulated in chronic gastritis regardless of H. pylori infection, because both infected and non-infected sample groups had reduced expression of these miRNAs. Other studies have shown down-regulation of miRNAs in inflammatory gastric lesions infected or non-infected by H. pylori (Matsushima et al, 2011;Shiotani et al, 2012); however, in gastric cancer some studies have reported increased expression of miRNAs such as miR-103, miR-181c, miR-370, miR-21 and miR-146a (Wu et al, 2011;An et al, 2013;Fan et al, 2013;Ishimoto et al, 2016). This different expression profile between gastric cancer and H. pylori infected gastric mucosa suggests that these miRNAs might act differently in the distinct stages of gastric tumorigenesis and disease progression.…”

miR 1296-5p Inhibits the Migration and Invasion of Gastric Cancer Cells by Repressing ERBB2 Expression

“…Despite the fact that advances have been made over the last decade, the underlying molecular mechanism of gastric cancer metastasis remains obscure [1, 2]. Currently, the signaling pathway in its metastatic cascade has shifted into the spotlight of relevant studies that are organized to find a new treatment for gastric cancer and therefore lower its mortality [3].…”

“…MicroRNAs (miRNAs), a strain of 22-nt noncoding RNAs, play a decisive role in posttranscriptional gene regulation of gastric cancer, pertaining to cell survival, proliferation, differentiation, migration, invasion and metastasis [2]. For instance, miR-1296 has been proved of its potential linkage with breast cancer chemoresistance and self-renewal capability [4].…”

Distribution of somatic mutations of cancer-related genes according to microsatellite instability status in Korean gastric cancer

“…The identification of genomic alterations may provide insight into the mechanisms for oncogenic gastric pathways and is important to identify a tumor marker in GC. [2–6] …”

“…[6–8] The Cancer Genome Atlas recently published results of a comprehensive study of GC, which provides an invaluable resource upon which to interpret other related GC findings. A molecular classification scheme in that study defined 4 major genomic subtypes of GC: Epstein–Barr virus (EBV)-infected tumors, microsatellite instability (MSI) tumors, genomically stable tumors, and chromosomal instability (CIN) tumors.…”