miR-20b and miR-451a Are Involved in Gastric Carcinogenesis through the PI3K/AKT/mTOR Signaling Pathway: Data from Gastric Cancer Patients, Cell Lines and Ins-Gas Mouse Model

Abstract

Gastric cancer (GC) is one of the most common and lethal gastrointestinal malignancies worldwide. Many studies have shown that development of GC and other malignancies is mainly driven by alterations of cellular signaling pathways. MicroRNAs (miRNAs) are small noncoding molecules that function as tumor-suppressors or oncogenes, playing an essential role in a variety of fundamental biological processes. In order to understand the functional relevance of miRNA dysregulation, studies analyzing their target genes are of major importance. Here, we chose to analyze two miRNAs, miR-20b and miR-451a, shown to be deregulated in many different malignancies, including GC. Deregulated expression of miR-20b and miR-451a was determined in GC cell lines and the INS-GAS mouse model. Using Western Blot and luciferase reporter assay we determined that miR-20b directly regulates expression of PTEN and TXNIP, and miR-451a: CAV1 and TSC1. Loss-of-function experiments revealed that down-regulation of miR-20b and up-regulation of miR-451a expression exhibits an anti-tumor effect in vitro (miR-20b: reduced viability, colony formation, increased apoptosis rate, and miR-451a: reduced colony forming ability). To summarize, the present study identified that expression of miR-20b and miR-451a are deregulated in vitro and in vivo and have a tumor suppressive role in GC through regulation of the PI3K/AKT/mTOR signaling pathway.

The Role of miR-375-3p and miR-200b-3p in Gastrointestinal Stromal Tumors

“…MicroRNAs (miRNAs) are a class of small (22 nucleotides long), highly stable non-coding RNAs involved in post-transcriptional regulation of gene expression [ 7 ]. Deregulated miRNA expression profiles have been observed in virtually all major types of cancer, where they can act both as oncogenes or tumor suppressors and are associated with tumorigenesis, tumor progression, metastasis and drug resistance pathways [ 7 , 8 , 9 , 10 ]. Furthermore, miRNAs have been shown to exhibit a diagnostic or prognostic value and even have potential clinical implications for targeted gene therapy in cancer patients [ 11 , 12 , 13 ].…”

MiRNA-20b/SUFU/Wnt axis accelerates gastric cancer cell proliferation, migration and EMT

“…In addition, previous studies revealed that miRNA-20b expression was enhanced in GC tissue and was positively associated with lymph node metastasis [3]. Further, high level of miRNA-20b predicts poor survival for GC patients [24] and suppression of miRNA-20b displays an anti-tumor effect in vitro [25], suggesting the therapeutic potential of targeting miRNA-20b in GC. However, the oncogenic molecular mechanism of miRNA-20b is not well studied.…”

miR-20b-5p functions as tumor suppressor microRNA by targeting cyclinD1 in colon cancer

“…However, the role of miR-20b-5p in the pathogenesis of cancers is controversial. MiR-20b-5p has a tumor suppressive role in gastric cancer(GC) through regulation of the PI3K / AKT / mTOR signaling pathway [36] . Also, miR-20b-5p suppressed TGF-β1-induced migration and invasion of prostate cancer by up-regulating E-cadherin and down-regulating vimentin, leading to TGF-β1-induced inhibition of epithelial-to-mesenchymal transition (EMT) [31] .…”