Integrated analysis of the miRNA, gene and pathway regulatory network in gastric cancer

Abstract

Gastric cancer is one of the most common malignant tumors worldwide; however, the efficacy of clinical treatment is limited. MicroRNAs (miRNAs) are a class of small non-coding RNAs that have been reported to play a key role in the development of cancer. They also provide novel candidates for targeted therapy. To date, in-depth studies on the molecular mechanisms of gastric cancer involving miRNAs are still absent. We previously reported that 5 miRNAs were identified as being significantly increased in gastric cancer, and the role of these miRNAs was investigated in the present study. By using bioinformatics tools, we found that more than 4,000 unique genes are potential downstream targets of gastric cancer miRNAs, and these targets belong to the protein class of nucleic acid binding, transcription factor, enzyme modulator, transferase and receptor. Pathway mapping showed that the targets of gastric cancer miRNAs are involved in the MAPK signaling pathway, pathways in cancer, the PI3K-Akt signaling pathway, the HTLV-1 signaling pathway and Ras signaling pathway, thus regulating cell growth, differentiation, apoptosis and metastasis. Analysis of the pathways related to miRNAs may provides potential drug targets for future therapy of gastric cancer.

MicroRNAs and the PTEN/PI3K/Akt pathway in gastric cancer (Review)

“…Identifying molecular causes of GC is of great importance in pattern recognition and therapeutic strategies. The poor prognosis of patients with GC primarily results from late detection, aggressive progression, poor response to available therapies and relapse (6,8,49). Therefore, in the present review, it was discussed how miRNAs are involved in the regulation of gastric CSCs and tumor environment through PTEN/PI3K/Akt signaling, which bears resemblance to the 'seed' and 'soil' in GC pathogenesis (91), respectively.…”

“…MicroRNAs (miRNAs) represent a large group of conserved small non-coding RNAs (ncRNAs) with a length of 17-25 nucleotides, which bind to the 3'-untranslated region (UTR) of mRNAs of their target genes, silencing expression by cleaving the mRNA molecules or inhibiting their translation (1,5). In this manner, ~30% human genes are modulated by miRNAs; the majority are directly or indirectly implicated in signaling pathways fundamental in cellular activities, including proliferation, differentiation, apoptosis and migration (7,8). As a result, miRNAs are crucial regulators in the initiation and progression of various diseases, particularly cancer.…”

“…Genetic and epigenetic alterations occurring in a number of components of this pathway lead to its constitutive activation in human cancer, including GC (11,16). Furthermore, the PTEN/PI3K/Akt pathway may be regulated by miRNAs in GC, suggesting that this signaling serves an essential role in mediating oncogenic effects of dysregulated miRNAs during the onset and development of this disease (6,8). In the present review, the dysregulation and function of miRNAs, in addition to genetic alterations and the roles of the PTEN/PI3K/Akt pathway in GC are summarized.…”

Combining multi-dimensional data to identify key genes and pathways in gastric cancer

“…HTLV-1 is a retrovirus which has been implicated in the occurrence of adult T-cell leukaemia and tropical spastic paraparesis. Zhang et al (2016b) also identified HTLV-1 signaling pathway in gastric cancer, but the role of HTLV-1 in gastric cancer still needs further study. Progesterone-mediated oocyte maturation is a nongenomic signaling mediated by steroids.…”

MicroRNA-145 Inhibits Cell Migration and Invasion and Regulates Epithelial-Mesenchymal Transition (EMT) by Targeting Connective Tissue Growth Factor (CTGF) in Esophageal Squamous Cell Carcinoma

“…Regulating gene expression at the transcriptional level is the main function of miRNA; growing evidence indicates that miRNAs are abnormally expressed in various human cancers and they have significant effects on cancer progression and carcinogenesis [8–10]. As predicted by bioinformatic analyses, single miRNA has various targets; therefore, miRNAs are able to mediate numerous protein-coding genes and approximately one-third of human genes are regulated by miRNAs [11,12]. Among all miRNAs, down-regulated miR-145 has been observed in multiple types of cancers, including lung cancer [13], renal cell cancer [14], prostate cancer [15], bladder cancer [16], and colon cancer [17].…”