Construction and Comprehensive Analysis of a circRNA-miRNA-mRNA Regulatory Network to Reveal the Pathogenesis of Hepatocellular Carcinoma

Mo, Meile; Liu, Bihu; Luo, Yihuan; Tan, Jennifer Hui Juan; Zeng, Xi; Zeng, Xianmin; Huang, Dongping; Li, Changhua; Liu, Shun; Qiu, Xiaoqiang

doi:10.3389/fmolb.2022.801478

Cited by 4 publications

(3 citation statements)

References 65 publications

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“…The discovery of circRNA subsets has added a new layer of complexity to the alterations of gene expression associated with epigenetic changes, primarily via the ceRNA network comprised of various circRNA-miRNA-mRNA axes (Shen et al, 2015;Fontemaggi et al, 2021). The dysfunction of circRNA-miRNA-mRNA regulatory signal represents another important epigenetic-controlled mechanism of the pathogenic gene expression in human cancer, which are important nodes in cancer development (Tang et al, 2021;Mo et al, 2022). Mapping the circRNA-miRNA-mRNA network is an important way to elucidate the regulatory role of circRNA being investigated (Rengganaten et al, 2020;Pang et al, 2022).…”

Section: Discussionmentioning

confidence: 99%

Identification of circRNA-miRNA-mRNA network in luminal breast cancers by integrated analysis of microarray datasets

Huang¹,

Qian²,

Chu³

et al. 2023

Front. Mol. Biosci.

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Introduction: Circular RNAs (circRNAs) regulatory network is important in human cancer. We, therefore, mapped the regulatory networks driven by circRNA in luminal-subtype breast cancer.Methods: Breast cancer-related microarray datasets from GEO database were analyzed for the differentially expressed circRNAs, miRNAs, and mRNAs. The potential downstream RNAs were collected using Circular RNA Interactome or Targetscan database. Protein-protein interaction (PPI) analysis was performed for the filtered genes to identify hub genes. The functions were annotated by the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. CircRNA-miRNA-mRNA networks were mapped using Cytoscape software. Hsa_circ_0086735-miR-1296-5p-STAT1 axis was used for verification. The expression levels of hsa_circ_0086735, miR-1296-5p, and STAT1 mRNA were confirmed by qRT-PCR in luminal-subtype tissues and cell lines. The interactions among them were verified by Luciferase reporter assay and RNA pull-down assay. Cell proliferation and apoptosis were assayed. Overall and distant metastasis-free survival was analyzed.Results: A total of 70 genes were finally targeted and enriched in multi-process and multi-pathway. Networks containing 96 circRNA-miRNA-mRNA axes were constructed. Hsa_circ_0086735 and STAT1 mRNA was upregulated in luminal breast cancer, while miR-1296-5p was downregulated. Hsa_circ_0086735-miR-1296-5p-STAT1 axis promotes breast cancer progression and contributes to tamoxifen resistance. High hsa_circ_0086735 was associated with poor overall and distant metastasis-free survival.Discussion: This study identified the hsa_circ_0086735-miR-1296-5p-STAT1 as an important regulatory axis in luminal-subtype breast cancer, aiding to determine potential therapeutic targets.

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Section: Discussionmentioning

confidence: 99%

Identification of circRNA-miRNA-mRNA network in luminal breast cancers by integrated analysis of microarray datasets

Huang¹,

Qian²,

Chu³

et al. 2023

Front. Mol. Biosci.

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“…Circular RNA (circRNA) is a type of non-coding RNA with a closed-loop structure that was first discovered in eukaryotes in 1976 [6]. Circular RNAs (circRNAs) have a high expression level, high stability, and tissue specificity [7,8]. They regulate linear RNA transcription and protein translation, performing a variety of different biological functions [9].…”

Section: Introductionmentioning

confidence: 99%

CircRNA Hsa_circ_0120175 Promotes Ovarian Cancer Tumorigenesis and Predicts a Poor Prognosis

Xing,

Chen,

Ding

et al. 2024

Discovery Medicine

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Background: Circular RNA is a type of non-coding RNA that is commonly found in eukaryotic genomes. They play an essential role in the biological processes of cell proliferation and cell apoptosis involved in normal development and abnormal tumorigenesis. In this study, we examined whether that the circular RNA GENE hsa_circ_0120175 is substantially expressed in epithelial ovarian cancer, and then explored whether hsa_circ_0120175 plays an important role in the occurrence and development of ovarian cancer. Methods: A total of 40 patients with ovarian cancer were included in this study, and tissue samples were collected from both ovarian cancer tissues and paracancer tissues. The levels of hsa_circ_0120175 expression were determined using qRT-PCR in both varian cancer cells and tissues. This study assessed the impact of hsa_circ_0120175 on cellular proliferation, migration, and invasion using various in vitro assays with cultured ovarian carcinoma cells. Results: Hsa_circ_0120175 was highly expressed in both human tissues and ovarian cancer cells. In ovarian cancer patients, the expression level of hsa_circ_0120175 was significantly different among The International Federation of Gynecology and Obstetrics (FIGO) stages (p = 0.03), and the difference was statistically significant. Multivariate Cox regression analysis showed that lymph node metastasis was independently related to Overall Survival (OS), and the difference was statistically significant (p = 0.033). In vitro, decreasing hsa_circ_0120175 significantly reduced ovarian carcinoma cell proliferation, migration, and invasion (p < 0.05).Conclusions: Hsa_circ_0120175 has the potential to serve as a biomarker for diagnosing and treating ovarian carcinoma. This is because it promotes cellular proliferation, migration, and invasion in epithelial ovarian carcinoma.

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“…Notably, previous studies revealed that circRNAs participate in cancer pathogenesis by sponging miRNAs that target mRNA and circRNAs exhibit potential as predictive biomarkers and therapeutic targets for cancer treatment (5,6). In addition, a previous study demonstrated that circRNA/miRNA/mRNA networks are involved in the development and progression of multiple types of malignancy (7). Results of a meta-analysis demonstrated that nine circRNAs may serve as potential prognostic markers for HNSCC and these are associated with lower overall survival (OS) and poor clinicopathological outcomes in patients with HNSCC (8).…”

Section: Introductionmentioning

confidence: 99%

Integrated analysis of high‑throughput sequencing reveals the regulatory potential of hsa_circ_0035431 in HNSCC

Liu,

Zeng,

Wang

et al. 2023

Oncol Lett

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Circular RNAs (circRNAs) are molecular sponges that are involved in regulation of multiple types of cancer. The present study aimed to screen and explore the key circRNA/microRNA (miRNA or miR)/mRNA interactions in head and neck squamous cell carcinoma (HNSCC) using bioinformatics. A total of six pairs of cancerous and adjacent healthy tissue were obtained from patients with HNSCC and genome-wide transcriptional sequencing was performed. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed on differentially expressed genes (DEGs). Moreover, expression levels of DEGs were verified in HNSCC cells and tissues using reverse transcription-quantitative (RT-q)PCR. A molecular regulatory network consisting of three circRNAs, seven miRNAs and seven mRNAs was constructed, resulting in identification of two signaling axes, hsa_circ_0035431/hsa-miR-940/fucosyltransferase 6 (FUT6) and hsa_circ_0035431/hsa-miR-940/cingulin-like 1 (CGNL1). FUT6 and CGNL1 were downregulated in HNSCC compared with adjacent healthy tissue and the expression levels of these genes were associated with tumor stage. Low FUT6 and CGNL1 expression levels were associated with lower overall survival rate and progression-free intervals in HNSCC.RT-qPCR demonstrated that hsa_circ_0035431, FUT6 and CGNL1 were downregulated in HNSCC cells and tissue and hsa-miR-940 was upregulated. Notably, these results were consistent with those obtained using high-throughput sequencing. In conclusion, hsa_circ_0035431 may participate in regulation of FUT6 and CGNL1 expression by sponging hsa-miR-940, thus, impacting the occurrence, development and prognosis of HNSCC.

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Construction and Comprehensive Analysis of a circRNA-miRNA-mRNA Regulatory Network to Reveal the Pathogenesis of Hepatocellular Carcinoma

Cited by 4 publications

References 65 publications

Identification of circRNA-miRNA-mRNA network in luminal breast cancers by integrated analysis of microarray datasets

Identification of circRNA-miRNA-mRNA network in luminal breast cancers by integrated analysis of microarray datasets

CircRNA Hsa_circ_0120175 Promotes Ovarian Cancer Tumorigenesis and Predicts a Poor Prognosis

Integrated analysis of high‑throughput sequencing reveals the regulatory potential of hsa_circ_0035431 in HNSCC

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