Three-microRNA signature identified by bioinformatics analysis predicts prognosis of gastric cancer patients

Zhang, Cheng; Ma, Ming; Dai, Dong‐Qiu

doi:10.3748/wjg.v24.i11.1206

Cited by 36 publications

(28 citation statements)

References 35 publications

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“…In addition, Pan et al (34) highlighted that the expression levels of miR-374 were decreased in glioma tissues and were associated with the prognosis of glioma patients, which is consistent with the results of the present study. It has been reported that the aberrant expression of certain miRNAs is associated with the development of cancer via the abnormal regulation of multiple BPs and signaling pathways (35). To further elucidate the molecular function of miR-374a and its target genes, functional enrichment analyses of the target genes in GO terms and KEGG pathways were performed.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of microRNA‑374a predicts poor prognosis in human glioma

et al. 2019

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Certain microRNAs (miRNAs/miRs) may be used as prognostic biomarkers in various types of cancer. The purpose of the present study was to identify miRNAs that were abnormally expressed in glioma of different grades, and to evaluate their clinical implications in patients with glioma. The differentially expressed miRNAs were evaluated from the expression profiles of six glioma tissues (three low-grade and three high-grade gliomas) determined using a microarray platform. Reverse transcription-quantitative polymerase chain reaction analysis was used to further verify the aberrant expression of the candidate miRNA in a set of 42 patients and 5 healthy controls. The miRNA target genes were predicted and the protein-protein interaction network was generated; furthermore, functional enrichment analysis of the target genes in Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways was performed. Kaplan-Meier curves and Log-rank analysis, as well as multivariate Cox regression analysis were performed to assess the association of the candidate miRNA with patient survival. A total of 15 differentially expressed miRNAs, including 13 downregulated and 2 upregulated miRNAs, were identified by comparison of low-grade and high-grade glioma tissues. The miR-374a expression of high-grade gliomas was significantly lower than that of low-grade gliomas (fold change, -4.43; P=0.027). The expression levels of miR-374a gradually decreased with the increase of the pathological grade of glioma. Pearson's Chi-square test was used to determine the association of miR-374a expression with several clinicopathological factors. Furthermore, low expression of miR-374a was determined to be an independent prognostic marker and that it was significantly associated with overall survival (P=0.0213). GO and KEGG pathway analysis revealed that the target genes of miR-374a may be involved in the regulation of the RNA polymerase II promoter and mTOR signaling pathway. The four hub genes (CCND1, SP1, CDK4, CDK6) were also identified by PPI network analysis. In conclusion, the present study indicated that miR-374a may be used as a promising prognostic biomarker for the screening of high-risk populations and for the assessment of the prognosis of patients with glioma.

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Section: Discussionmentioning

confidence: 99%

Downregulation of microRNA‑374a predicts poor prognosis in human glioma

et al. 2019

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“…MiR-23b-3p was downregulated in colon cancer and mediated tumor metastasis by regulating FZD7 and MAP3K1 [57]. In addition, studies also found that miR-23b-3p was upregulated in GC tissues [58]. Previous studies indicated that miR-130a-3p was downregulated and inhibited cancer in many cancers [59][60][61][62].…”

Section: Discussionmentioning

confidence: 98%

Identification of Key Genes and MicroRNAs in Gastric Cancer via miRNA-mRNA Regulatory Network

Huang

Zhu

Zhao

et al. 2020

Preprint

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Background Gastric cancer (GC) is a malignant tumor with high mortality. MicroRNAs (miRNAs) participate in various biological processes and disease pathogenesis by targeting messenger RNA (mRNA). The purpose of this study was to identify potential prognostic molecular markers of GC and to characterize the molecular mechanisms of GC. Methods A gene expression profiling dataset (GSE54129) and miRNA expression profiling dataset (GSE113486) were downloaded from the Gene Expression Omnibus (GEO) database. A miRNA-mRNA interaction network was established. Functional and pathway enrichment analyses were performed for differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) using FunRich, the clusterProfiler package, and DIANA-mirPath. Survival analysis of key molecular markers was performed using the online tool Kaplan-Meier Plotter and the database OncomiR. Finally, experiments were carried out to verify the expression levels and biological functions of a key gene. Results A total of 390 DEMs and 341 DEGs were identified. Ultimately, 45 genes and 31 miRNAs were selected to establish a miRNA-mRNA regulatory network. Four hub genes (ZFPM2, FUT9, NEUROD1 and LIPH) and six miRNAs (hsa-let-7d-5p, hsa-miR-23b-3p, hsa-miR-23a-3p, hsa-miR-133b, hsa-miR-130a-3p and hsa-miR-124-3p) were identified in the network. DEGs and DEMs were associated with ECM-receptor interactions and metabolic pathways. Two genes (ZFPM2 and LIPH) and two miRNAs (hsa-miR-23a-3p and hsa-miR-130a-3p) were observed to be related to the prognosis of GC. ZFPM2 was highly expressed in GC tissues and various GC cell lines and could promote the proliferation, invasion and migration of GC cells. Conclusion The expression levels of ZFPM2, LIPH, hsa-miR-23a-3p and hsa-miR-130a-3p were closely related to the prognosis of GC. ZFPM2 may serve as a potential molecular marker and therapeutic target for GC. ECM receptor interactions and metabolic abnormalities play a critical role in the GC progression.

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“…Potential targets of miR-4429 were predicted based on TargetScan and miRDB databases. 18 WT-FOXM1 and Mut-FOXM1 plasmids were constructed. ME-180 and C33A cells were seeded into a 24-well plate at 5×10 3 per well, and transfected when their confluency reached 90%.…”

Section: Luciferase Reporter Gene Assaymentioning

confidence: 99%

<p>miR-4429 Regulates the Proliferation, Migration, Invasion, and Epithelial-Mesenchymal Transition of Cervical Cancer by Targeting FOXM1</p>

Liang¹,

Zheng²,

Wang³

2020

CMAR

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Background: miR-4429 acts as an inhibitor in many malignant tumors and participates in the biological processes of them, but the clinical value and potential molecular mechanism of miR-4429 in cervical cancer (CC) are still under investigation. Objective: To analyze the clinical value and molecular mechanism of miR-4429 in CC. Materials and Methods: A qRT-PCR assay was employed to determine the levels of miR-4429 and forkhead-box M1 (FOXM1) in CC tissues, CC cell lines (SiHa, CaSki, ME-180, and C33A) and human normal immortalized epithelial cell lines (HaCaT). The proliferation, migration, invasion, and apoptosis abilities of ME-180 and C33A cells were detected, and the epithelial-to-mesenchymal transition (EMT)-related proteins in the cells were also determined. Results: MiR-4429 acted as a tumor suppressor gene in CC tissues and cells and was linked to lymph node metastasis and International Federation of Gynecology and Obstetrics (FIGO) staging. The survival analysis revealed that lymph node metastasis, high FIGO staging, and low miR-4429 expression were all related to the unfavorable prognosis of the patients, and the dual-luciferase reporter assay revealed that FOXM1 was the target of miR-4429. Both overexpression of miR-4429 and knock-down of FOXM1 inhibited the proliferation, migration, invasion, and EMT of CCCs, and accelerated the apoptosis of them. Conversely, both knockdown of miR-4429 and overexpression of FOXM1 promoted those biological behaviors of the cells. Moreover, the rescue experiment revealed that the overexpression of FOXM1 reversed the influences of miR-4429 overexpression on the proliferation, migration, invasion, and EMT of CCCs. Conclusion: miR-4429 acts as a tumor suppressor in CC and can directly target FOXM1 to regulate the proliferation, migration, invasion, apoptosis and EMT of CCCs, so miR-4429 is expected to be a new therapeutic target for CC.

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Three-microRNA signature identified by bioinformatics analysis predicts prognosis of gastric cancer patients

Cited by 36 publications

References 35 publications

Downregulation of microRNA‑374a predicts poor prognosis in human glioma

Downregulation of microRNA‑374a predicts poor prognosis in human glioma

Identification of Key Genes and MicroRNAs in Gastric Cancer via miRNA-mRNA Regulatory Network

<p>miR-4429 Regulates the Proliferation, Migration, Invasion, and Epithelial-Mesenchymal Transition of Cervical Cancer by Targeting FOXM1</p>

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