Dataset Information

PHLPP2 is regulated by competing endogenous RNA network in pathogenesis of colon cancer.

ABSTRACT: Recently, homologous pleckstrin-homology (PH)-domain leucine-rich-repeat protein phosphatases (PHLPP2) has been reported as a tumor suppressor in colon cancer. This study aimed to unravel the possible involvement of long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) regulating PHLPP2 in colon cancer. Expressions of candidate lncRNAs and miRNAs were verified by the RT-qPCR and Western blot analyses in colon cancer. The roles of candidate genes in colon cancer were investigated in HT-29 cells in vitro and in mouse tumor xenograft model in vivo. PHLPP2, a target of miR-141 and miR-424, was downregulated in colon cancer. PHLPP2 upregulation and miR-141 and miR-424 downregulation suppressed the colon cancer cell proliferation, migration, invasion, and epithelial-mesenchymal transition, and promote cell apoptosis, which also resulted in suppression of tumor metastasis and formation. Furthermore, LINC00402, LINC00461, and SFTA1P were identified as the targets of miR-141 and miR-424 and acted as competitive endogenous RNAs (ceRNAs) of PHLPP2. The upregulation of LINC00402, LINC00461, and SFTA1P was verified to enhance the suppressive effects of PHLPP2 in the pathogenesis of colon cancer. Conjointly, our results demonstrated the suppressive effects of PHLPP2 in colon cancer and proved that LINC00402, LINC00461, and SFTA1P acted as ceRNAs of PHLPP2 by competitive binding to miR-141 and miR-424.

SUBMITTER: Wu HK

PROVIDER: S-EPMC7377866 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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PHLPP2 is regulated by competing endogenous RNA network in pathogenesis of colon cancer.

Wu Hong-Kun HK Liu Chang C Li Xin-Xing XX Ji Wei W Xin Chen-De CD Hu Zhi-Qian ZQ Zhou Lin L

Aging 20200707 13

Recently, homologous pleckstrin-homology (PH)-domain leucine-rich-repeat protein phosphatases (PHLPP2) has been reported as a tumor suppressor in colon cancer. This study aimed to unravel the possible involvement of long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) regulating PHLPP2 in colon cancer. Expressions of candidate lncRNAs and miRNAs were verified by the RT-qPCR and Western blot analyses in colon cancer. The roles of candidate genes in colon cancer were investigated in HT-29 cells <i ...[more]

PMID: 32633726

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Project description:Phospholipase C epsilon 1 (PLCE1) and the competing endogenous RNA (ceRNA) network are crucial for tumorigenesis and the progression of esophageal squamous cell carcinoma (ESCC). However, whether PLCE1 can regulate the ceRNA network in ESCC has not been clarified. In the present study, we aimed to identify the PLCE1‑regulated ceRNA network and further elucidate the regulatory mechanisms by which ESCC is promoted. Microarray analysis was used to identify differentially expressed lncRNAs (DELs) and differentially expressed genes (DEGs) from three pairs of samples of PLCE‑silenced Eca109 and control Eca109 cells. Next, the ceRNA regulatory network was established and visualized in Cytoscape, and functional enrichment analysis was performed to analyze DEGs from ceRNAs. Protein‑protein interaction (PPI) networks among the DEGs were established by the STRING database to screen hub genes. Kaplan‑Meier survival analysis was used to validate hub genes. Finally, PLCE1‑related hub gene/lncRNA/miRNA axes were also constructed based on the ceRNA network. A total of 105 DELs and 346 DEGs were found to be dysregulated in the microarray data (|log2FC| >1.5, adjusted P<0.05). We constructed a PLCE1‑regulated ceRNA network that incorporated 12 lncRNAs, 43 miRNAs, and 169 mRNAs. Functional enrichment analysis indicated that the DEGs might be associated with ESCC onset and development. A PPI network was established, and 9 hub genes [WD and tetratricopeptide repeats 1 (WDTC1), heat shock protein family A (Hsp70) member 5 (HSPA5), N‑ethylmaleimide sensitive factor, vesicle fusing ATPase (NSF), fibroblast growth factor 2 (FGF2), cyclin dependent kinase inhibitor 1A (CDKN1A or P21), bone morphogenetic protein 2 (BMP2), complement C3 (C3), GM2 ganglioside activator (GM2A) and discs large MAGUK scaffold protein 4 (DLG4)] were determined from the network. Kaplan‑Meier survival analysis validated four hub genes (BMP2, CDKN1A, GM2A, and DLG4) that were treated as prognostic factors. Ultimately, hub gene/lncRNA/miRNA subnetworks were obtained based on the 4 hub genes, 13 DEmiRNAs, and 10 DELs. In conclusion, the PLCE1‑regulated ceRNA contributes to the onset and progression of ESCC and the underlying molecular mechanisms may provide insights into personalized prognosis and new therapies for ESCC patients.

Project description:BackgroundOsteoarthritis (OA) is one of the most common diseases in elderly people; however, the correlation between molecular alterations and the occurrence and progression of OA are still not well understood. We conducted this study to investigate the molecular changes in OA via the competing endogenous ribonucleic acid (ceRNA) network.MethodsWe downloaded the messenger RNA (mRNA) data set, GSE48556, the microRNA (miRNA) data set, GSE105027, and the long non-coding (lncRNA) data set, GSE126963 from the Gene Expression Omnibus (GEO) database, and examined the differentially expressed genes (DEGs) in these data sets. Further, we constructed a ceRNA network of the differentially expressed miRNAs, mRNAs, and lncRNAs. To determine the biological functions of the ceRNA network, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses. Finally, we conducted an immune cell infiltration analysisusing single-sample gene set enrichment analysis to examine the abundance of immune cells in healthy and OA patients, and compared the infiltration of 28 immune cells between the healthy and OA samples. We also analyzed the relationship between the abundance of immune cells and mRNA expression levels in the ceRNA network.ResultsUltimately hsa-mir-425-3p, dual specificity phosphatase 1, and 24 lncRNAs were identified in the ceRNA network. The functional enrichment analyses showed that these lncRNAs, miRNAs, and mRNAs are involved in various significant biological process, such as the regulation of leukocyte migration, Mitogen-Activated Protein (MAP) kinase tyrosine/serine/threonine phosphatase activity, the interleukin-17 signaling pathway, the tumor necrosis factor signaling pathway, and osteoclast differentiation, and can also have a strong effect on immune cell infiltration.ConclusionsThe dual-specificity phosphatase 1-specific ceRNA network can be used as a diagnostic tool to assess the progression of OA patients.

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PHLPP2 is regulated by competing endogenous RNA network in pathogenesis of colon cancer.

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PHLPP2 is regulated by competing endogenous RNA network in pathogenesis of colon cancer.

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