Post-Transcriptional Dysregulation of microRNA and Alternative Polyadenylation in Colorectal Cancer

Mao, Zhanrui; Zhao, Hui; Qin, Yanmin; Wei, Jianming; Sun, Jingyong; Zhang, Weiwei; Kang, Yani

doi:10.3389/fgene.2020.00064

Cited by 29 publications

(22 citation statements)

References 37 publications

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“…This study found that hsa-mir-1200 was signi cantly associated with poor survival. hsa-mir-145 affected circular RNA expression in prostate cancer [24], glioblastoma cell [25], bladder cancer [26,27], and colorectal cancer [28]. In CSCC, we showed that hsa-mir-145 overexpression had a better overall survival.…”

Section: Discussionmentioning

confidence: 80%

Identification of a novel circRNA, hsa_circ_0065898, that regulates tumor growth in cervical squamous cell carcinoma

Liu

Deng³

2020

Preprint

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Background: Circular RNAs (circRNAs) have been reported to play an important role in regulating tumor pathogenesis and progression. The molecular mechanism of circRNAs in cervical squamous cell carcinoma (CSCC) remains poorly understood. We aimed to identify the circRNAs differentially expressed, and to investigate the role of a novel circRNA, hsa_circ_0065898, in regulating proliferation, migration, and invasion in CSCC.Methods: The online Kaplan-Meier Plotter was used to analyze the relationship between miRNA expression and overall survival. Bioinformatics tools, such as R, Cytoscape, and Perl, were used to analyze the Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, protein-protein interaction (PPI) network, and regulatory network. The expression level of hsa_circ_0065898 in CSCC cell lines was evaluated using quantitative polymerase chain reaction in vitro. The cell counting kit-8 (CCK-8) and transwell assays were used to assess cell proliferation, migration, and invasion. Results: circRNA expression data (GSE102686) was downloaded from the Gene Expression Omnibus database, and this included data from 5 CSCC patients and 5 normal tissues. Thirteen differentially expressed circRNAs were identified, which included 9 upregulated circRNAs and 4 downregulated circRNAs. GO enrichment analysis showed that the target genes of miRNAs associated with hsa_circ_0065898 were enriched in ubiquitin-protein transferase activity, ubiquitin-like protein transferase activity, core promoter sequence-specific DNA binding, mRNA 3′-UTR AU-rich region binding, core promoter binding, AU-rich element binding, ubiquitin-like protein ligase activity, and transcription corepressor activity. KEGG results showed that the Hippo and p53 signaling pathways played significant role in the pathway network. Hsa_circ_0065898 was significantly overexpressed in the CSCC cell lines. Hsa_circ_0065898 facilitated cell proliferation, migration, and invasion in CSCC.Conclusions: This study identified differentially expressed circRNAs and constructed the regulatory network of hsa_circ_0065898 targeting microRNAs and mRNAs. We demonstrated that hsa_circ_0065898 promoted CSCC cell proliferation, migration, and invasion. Hence, hsa_circ_0065898 might be useful as a biomarker for CSCC diagnosis and targeted therapy.

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Section: Discussionmentioning

confidence: 80%

Identification of a novel circRNA, hsa_circ_0065898, that regulates tumor growth in cervical squamous cell carcinoma

Liu

Deng³

2020

Preprint

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“…Even more, the same related immune pathway, Cytokines pathway, was found among MEG8 and SOBP. In previous studies, hsa-miR-378d was upregulated in colorectal cancer and might be a potential biomarker in diagnosis [52,53]. MEG8 suppresses activation of epithelial-mesenchymal transition of hepatocytes by the Notch pathway [54].…”

Section: Discussionmentioning

confidence: 94%

Identification of MEG8-miR378d-SOBP Axis as a Novel Regulatory Network and Associated With Immune Infiltrates in Ovarian Carcinoma by Integrated Bioinformatics Analysis

Lei

Wang

et al. 2020

Preprint

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BackgroundTo investigate the potential molecular mechanism of ovarian cancer (OC) evolution and immunological correlation using the integrated bioinformatics analysis.MethodsData from the Gene Expression Omnibus (GEO) was used to gain differentially expressed genes (DEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analysis were completed by utilizing the Database for Annotation, Visualization, and Integrated Discovery (DAVID). After multiple validation via The Cancer Genome Atlas (TCGA), Gene Expression Profiling Interactive Analysis 2 (GEPIA 2), the Human Protein Atlas (HPA) and Kaplan-Meier (KM) plotter, immune logical relationships of the key gene SOBP were evaluated based on Tumor Immune Estimation Resource (TIMER), and Gene Set Enrichment Analysis (GSEA) software. Finally, the lncRNAs-miRNAs-mRNAs sub-network was predicted by starBase, Targetscan, miRBD, and LncBase, individually. Correlation of expression and prognosis for mRNAs, miRNAs and lncRNAs were confirmed by TCGA, GEPIA 2, starBase, and KM.ResultsA total of 192 shared DEGs were discovered from the four data sets, including 125 upregulated and 67 downregulated genes. Functional enrichment analysis presented that they were mainly enriched in cartilage development, pathway in PI3K-Akt signaling pathway. Lower expression of SOBP was the independent prognostic factor for inferior prognosis in OC patients. Intriguingly, downregulated SOBP enhanced the infiltration levels of B cells, CD8+ T cells, Macrophage, Neutrophil and Dendritic cells. GSEA also disclosed low SOBP showed significantly association with the activation of various immune-related pathways. Finally, we firstly reported that MEG8-miR378d-SOBP axis was linked to development and prognosis of ovarian cancer through regulating cytokines pathway.Conclusions Our study establishes a novel MEG8-miR378d-SOBP axis in the development and prognosis of OC, and the triple sub-network probably affects the progression of ovarian tumor by regulating cytokines pathway.

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“…There have already been various studies providing ideas about the importance of miRNA-mRNA interacting pairs in CRC from different directions. Zhou et al, obtained 372 pairs of miRNA-mRNA, furtherly analyzed the potential roles in CRC development, and finally determined the significant influence of three miRNAs on the prognosis of CRC patients (Zhou et al, 2015); Mao et al revealed the post-transcriptional dysregulation of miRNAs in CRC partly through assessing the interactions between miRNAs and alternative polyadenylation (Mao et al, 2020). In this study, overlapping the predicted targets of DE miRNAs with the reversely expressed DE mRNAs, the networks were successfully established of DE miRNAs and DE mRNAs consisting of 42 upregulated DE-miRNAs/212 downregulated DE-mRNAs and 23 downregulated DE-miRNAs/103 upregulated DE mRNAs.…”

Section: Discussionmentioning

confidence: 99%

Establishment of a Colorectal Cancer-Related MicroRNA-mRNA Regulatory Network by Microarray and Bioinformatics

Jiang

Xie

et al. 2020

Front. Genet.

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Colorectal cancer (CRC) is one of the most malignant cancers with high morbidity and mortality. MicroRNAs (miRNAs) are small non-coding RNAs that affect biological processes by binding to mRNAs and regulating their expression, and epigenetic alterations including miRNA dysregulation are significantly involved in CRC development. Determining the effect of the miRNA-mRNA network on CRC could be helpful for developing novel therapeutic targets and prognostic biomarkers, and even improving survival. In this study, microarray assays were used to screen differentially expressed miRNAs (DE miRNAs) and mRNAs (DE mRNAs) in CRC and the adjacent normal tissues. Among the detected genes, 42 miRNAs and 142 mRNAs were significantly upregulated in CRC, while 23 miRNAs and 279 mRNAs were significantly downregulated. Through overlapping of predicted targets of DE miRNAs and anti-expressed DE mRNAs, networks of DE miRNAs and DE mRNAs in CRC were established. Additionally, the formation of a protein-protein interaction network of DE mRNAs possibly targeted by DE miRNAs, functional annotation and pathway analysis, stable subnetwork mining, and determination of hub genes provided the probable mechanism used by DE miRNAs and DE mRNAs to regulate CRC growth. Finally, validation of expression and prognostic potential of hub genes provided further support for the results above and indicated that CCL-28, GPR15, PNOC, NUSAP1, and their interacted miRNAs may be a potential signature for prognosis of CRC patients. In sum, we successfully established miRNA-mRNA regulatory networks based on microarray results targeting CRC, and these findings may elucidate the mechanisms used for CRC growth and identify miRNA-related signatures for prognosis and treatment of CRC.

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Post-Transcriptional Dysregulation of microRNA and Alternative Polyadenylation in Colorectal Cancer

Cited by 29 publications

References 37 publications

Identification of a novel circRNA, hsa_circ_0065898, that regulates tumor growth in cervical squamous cell carcinoma

Identification of a novel circRNA, hsa_circ_0065898, that regulates tumor growth in cervical squamous cell carcinoma

Identification of MEG8-miR378d-SOBP Axis as a Novel Regulatory Network and Associated With Immune Infiltrates in Ovarian Carcinoma by Integrated Bioinformatics Analysis

Establishment of a Colorectal Cancer-Related MicroRNA-mRNA Regulatory Network by Microarray and Bioinformatics

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