Current perspectives on the dysregulated microRNAs in gastric cancer

Abstract

Since gastric cancer (GC) is diagnosed at advanced stages, the survival rate is low in affected people. In this regard, investigating the mechanisms underlying GC development, are so critical. MiRNAs, which are small non coding RNAs, as a post transcriptional repressor, regulate expression of target genes by stimulating breakage or transcription suppression of their targets therefore aberrant expression of miRNAs leading to GC carcinogenesis. In the last decades, there have been various studies approving the pivotal role of miRNAs in various phases of GC development including cancer initiation, proliferation, migration, invasion, metastasis, angiogenesis, apoptosis, and drug resistance. Therefore, the present review aimed at summarizing the dysregulated miRNAs which contribute to various cellular and developmental mechanisms such as, proliferation, apoptosis, invasion, migration, and angiogenesis. Moreover, it provides an overview on novel miRNAs involved in drug resistance and circular miRNAs as cancer biomarkers. Thereafter, it is hoped that the present study will shed more light on diagnostic and prognostic biomarkers of GC, and potential GC treatments based on miRNAs.

The Role and Expression of Angiogenesis-Related miRNAs in Gastric Cancer

“…PTEN is a tumor suppressor gene that negatively regulates mammalian target of rapamycin (mTOR) complex 1 (mTORC1) activity, which activates the translation of proteins. The restoration of PTEN expression may block angiogenesis in GC by inactivating the PI3K/protein kinase B (AKT) pathway [23]. Additionally, several miRNAs have been identified to target the Forkhead box O (FOXO) transcription factors and the tuberous sclerosis complex subunit 1 (TSC1) [23].…”

“…The restoration of PTEN expression may block angiogenesis in GC by inactivating the PI3K/protein kinase B (AKT) pathway [23]. Additionally, several miRNAs have been identified to target the Forkhead box O (FOXO) transcription factors and the tuberous sclerosis complex subunit 1 (TSC1) [23]. FOXO is a key substrate of AKT.…”

“…In this analysis, miR-1 was underexpressed in primary GC tissues when compared with adjacent normal mucosa and several GC cell lines. The restoration of miR-1 significantly inhibited endothelial cell tube formation by decreasing the expression of VEGF-A and endothelin 1 (EDN1), the main angiogenic factors contributing to the development and maintenance of blood vessels [23]. Additionally, the overexpression of miR-126 led to direct inhibition of VEGF-A expression, reduction of cell proliferation, and inhibition of the angiogenic process, thereby inhibiting tumor growth both in vitro and in vivo in GC [61][62][63].…”

“…In one study, miR-23a was augmented in HGC-27-derived exosomes, and facilitated angiogenesis by targeting PTEN, as verified by the elevated expression level of VEGF and the reduced expression level of the matricellular protein thrombospondin-1 (TSP-1) [23]. The same study demonstrated that the upregulation of another miRNA, miR-616-3p, in GC tissues resulted in the downregulation of PTEN and PI3K/AKT/mTOR pathway activation through PTEN, which then contributed to EMT and angiogenesis [23]. A second study confirmed the relevance of miR-23a, and a third study confirmed the relevance of miR-616-3p in GC [60,70].…”