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

Hu, Mingming; Zhu, Shixuan; Xiong, Shengwei; Xue, Xingxing; Zhou, Xiaodong

doi:10.3892/or.2019.6962

Cited by 93 publications

(82 citation statements)

References 89 publications

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“…During cancer cell migration, Paluch et al [27] proposed that adhesion to the matrix through a speci c site is an essential step. Additionally, the PI3K-Akt signaling pathway plays an important role in cell migration, angiogenesis, and survival in GC [28,29]. In GSEA enrichment, cancerrelated pathways, such as the TGF-β, MAPK and JAK2 signaling pathways, were signi cantly identi ed.…”

Section: Discussionmentioning

confidence: 99%

The TCGA and GEO databases identify COL5A2 as a poorly prognostic gene in patients with advanced gastric cancer

Tan

Chen

Xing

et al. 2020

Preprint

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Background Gastric cancer (GC) metastasis determines the prognosis of patients, and exploring the molecular mechanism of GC metastasis is expected to provide a theoretical basis for clinical treatment. Recent studies have shown that extracellular matrix protein is closely related to GC metastasis. This study aimed to explore the expression profile and role of COL5A2 (Collagen V-type α2), as an extracellular matrix protein, in GC. Methods The expression, overall survival and progression-free survival data of COL5 family members were extracted from The Cancer Genome Atlas(TCGA)database, respectively. Paraffin immunohistochemistry and RT-qPCR in GC and matched normal tissues were used to analyze the expression of the target genes. Weighted gene co-expression network analysis of the GSE62229 database was performed out to identify modules and associated genes, and the functions were predicted by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Results COL5A2 was selected as our research target in the TCGA database, and was also verified in the GSE62229 and GSE15459 datasets. COL5A2 was upregulated in GC tissues by paraffin immunohistochemistry and RT-qPCR. The analysis of clinicopathological characteristics showed a significant difference in the Borrmann type (P = 0.036), histological type (P = 0.013) and T stage(P = 0.011). The prognosis of patients with low COL5A2 expression was better than that of patients with high COL5A2 expression. GSEA results showed that the TCGA and GSE62229 samples were significantly enriched in several well-known cancer-related pathways, such as the TGF-β, MAPK, and JAK2 signaling pathways. Conclusion COL5A2 was most closely related to advanced GC among COL5 family members. High COL5A2 expression is associated with a poor prognosis in GC, and may be a novel therapeutic target for GC.

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Section: Discussionmentioning

confidence: 99%

The TCGA and GEO databases identify COL5A2 as a poorly prognostic gene in patients with advanced gastric cancer

Tan

Chen

Xing

et al. 2020

Preprint

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“…The PI3K/AKT pathway can be activated by a variety of factors including hormone and ECM pathways, thereby regulating multiple fundamental cellular activities such as cell proliferation, apoptosis and metastasis [68]. As the most common dysregulation pathway in cancer, the PI3K/AKT pathway has received increasing attention due to its potential for target therapy in many malignancies [69]. We proposed that CKI plays a therapeutic role in the treatment of GC that is mediated by PI3K-AKT pathway, and it has been experimentally con rmed earlier.…”

Section: Discussionmentioning

confidence: 99%

A novel multi-scale bioinformatics strategy for identifying the molecular mechanism by insighting into ceRNA network integrating WGCNA and meta-analysis: compound kushen injection for treating gastric carcinoma as a proof

Zhou

Zhang

Guo

et al. 2020

Preprint

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BackgroundGastric carcinoma (GC) is a severe digestive system tumor with high morbidity and mortality and poor prognosis, of which the novel treatments are urgently needed. Compound kushen injection (CKI), a classic Chinese medicine injection, has been widely used to treat a variety of tumors in clinical for decades. In recent years, a growing number of studies have confirmed that CKI has a favorable therapeutic effect on GC, but there are few reports on the potential molecular mechanism of action.MethodsHere, using network pharmacology as the core concept, we identified the ceRNA network and key targets of CKI in the treatment of GC. In order to further explore the impact of key targets, we conducted a meta-analysis of them and compared the expression differences between GC tissues and normal tissues. Functional analysis was utilized to understand the biological regulation pathways involved in key genes. Moreover, we further detected the significance of key genes for the prognosis of GC through survival analysis and immune infiltration analysis. Finally, molecular docking simulation was adopted so as to verify the combination of CKI components and key targets.ResultsAnalysis of the ceRNA network of CKI on GC illustrated that the potential molecular mechanism of CKI was possible to regulate PI3K-AKT and Toll-like receptor signaling pathways by intervening hub genes including AKR1B1, MMP2 and PTGERR3.ConclusionsIn conclusion, this study not only partially highlighted the molecular mechanism of CKI in GC therapy but also provided a novel strategy for exploring the effective mechanisms of traditional Chinese medicine formulations.

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“…Though the role of miR-107 is controversial in GC, our study proved that miR-107 was up-regulated in GC and was negatively correlated with the expression of PCAT18. Multiple miRNAs has been found to regulate PTEN/PI3K/Akt pathway in GC, 23 activated PI3K phosphorylates phosphatidylinositol-4,5-bisphosphate (PIP2) to form phosphatidylinositol-3,4,5-trisphosphate (PIP3). Akt is the downstream of PIP3, in which Akt is phosphorylated and stimulated by other kinases.…”

Section: Discussionmentioning

confidence: 99%

<p>The Down-Regulation of lncRNA PCAT18 Promotes the Progression of Gastric Cancer via MiR-107/PTEN/PI3K/AKT Signaling Pathway</p>

Chen

Zhao

Wang

et al. 2019

OTT

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Purpose: LncRNAs are important regulators in cancers. In this study, we investigated the role of lncRNA PCAT18 in gastric cancer (GC). Patients and Methods: The level of PCAT18 in GC tissues and cells was determined by qRT-PCR. The cellular behaviors of GC cells with knockdown or overexpression of PCAT18 were respectively detected by CCK-8 assays, colony formation assays, flow cytometry and Western blot. A GC mice model was established by subcutaneous injection of MGC-803 and HGC-27 cells with the knockdown or overexpression of PCAT18. The tumor size and weight were measured, and IHC was performed to determine ki-67 level. Predicted by bioinformatics software and confirmed by dual-luciferase reporter assay, PCAT18 was involved in miR-107/PTEN axis, thus, the expression of and relationship among PCAT18, miR-107 and PTEN pathway were explored in clinical cases and GC cell lines. Rescue assay was performed in GC cells by co-transfection with miR-107 mimic or PCAT18. The PTEN/ PI3K/AKT pathway was then detected by Western blot. Results: PCAT18 was down-regulated in GC tissues and cells, and it had a significant diagnostic value for GC. The expression of PCAT18 was highly associated with tumor size, and PCAT18 was found to inhibit GC growth in vitro and in vivo. It was also found that PCAT18 was involved in PTEN/PI3K/AKT signaling pathway through targeting miR-107. Conclusion: PCAT18 inhibits the progression of GC via miR-107/PTEN/PI3K/AKT signaling pathway. Additionally, PCAT18 is possibly a promising target for treatment of GC.

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

Cited by 93 publications

References 89 publications

The TCGA and GEO databases identify COL5A2 as a poorly prognostic gene in patients with advanced gastric cancer

The TCGA and GEO databases identify COL5A2 as a poorly prognostic gene in patients with advanced gastric cancer

A novel multi-scale bioinformatics strategy for identifying the molecular mechanism by insighting into ceRNA network integrating WGCNA and meta-analysis: compound kushen injection for treating gastric carcinoma as a proof

<p>The Down-Regulation of lncRNA PCAT18 Promotes the Progression of Gastric Cancer via MiR-107/PTEN/PI3K/AKT Signaling Pathway</p>

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