Discovering master regulators in hepatocellular carcinoma: one novel MR, SEC14L2 inhibits cancer cells

Li, Zhihui; Liu, Yi; Tian, Guoyan; Wu, Jianyue; Lu, Anqian; Chen, Jin; Xu, Beibei; Shi, Junping; Yang, Jin

doi:10.18632/aging.102579

Cited by 15 publications

(10 citation statements)

References 56 publications

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“…For the analysis, we used CoRegNet 24 , a tool for network inference based on TF influence estimation. The tool CoRegNet has successfully been used to identify driver regulators for bladder cancer 36 , master regulators in fatty liver disease 37 and hepatocellular carcinoma 38 and sex-specific gene regulation in drosophila 39 , among other studies. Two additional software was used for calculating TF activities of the samples, for seeing if we could retrieve the TFs already identified with CoRegNet, independently of the reference network.…”

Section: Discussionmentioning

confidence: 99%

Identification of putative master regulators in rheumatoid arthritis synovial fibroblasts using gene expression data and network inference

Zerrouk

Miagoux

Dispot

et al. 2020

Sci Rep

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Rheumatoid arthritis (RA) is a systemic autoimmune disease that affects the synovial joints of the body. Rheumatoid arthritis fibroblast-like synoviocytes (RA FLS) are central players in the disease pathogenesis, as they are involved in the secretion of cytokines and proteolytic enzymes, exhibit invasive traits, high rate of self-proliferation and an apoptosis-resistant phenotype. We aim at characterizing transcription factors (TFs) that are master regulators in RA FLS and could potentially explain phenotypic traits. We make use of differentially expressed genes in synovial tissue from patients suffering from RA and osteoarthritis (OA) to infer a TF co-regulatory network, using dedicated software. The co-regulatory network serves as a reference to analyze microarray and single-cell RNA-seq data from isolated RA FLS. We identified five master regulators specific to RA FLS, namely BATF, POU2AF1, STAT1, LEF1 and IRF4. TF activity of the identified master regulators was also estimated with the use of two additional, independent software. The identified TFs contribute to the regulation of inflammation, proliferation and apoptosis, as indicated by the comparison of their differentially expressed target genes with hallmark molecular signatures derived from the Molecular Signatures Database (MSigDB). Our results show that TFs influence could be used to identify putative master regulators of phenotypic traits and suggest novel, druggable targets for experimental validation.

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Section: Discussionmentioning

confidence: 99%

Identification of putative master regulators in rheumatoid arthritis synovial fibroblasts using gene expression data and network inference

Zerrouk

Miagoux

Dispot

et al. 2020

Sci Rep

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“…SEC14L2-like phosphatidylinositol transfer proteins SEC14L3/SEC14L2 mediated Wnt/Ca 2+ signaling by acting as GTPase proteins. 95 SLC6A1 is overexpressed in prostate cancer and is associated with drug resistance and a poor prognosis 96 but is downregulated in HCC. 97 SEC14L2 and SLC6A1 mRNAs serve as novel transcriptional targets related to Myc and suppress HCC progression and thus may be a promising target for the treatment of Myc-driven HCC.…”

Section: Discussionmentioning

confidence: 99%

Construction of a Myc-associated ceRNA network reveals a prognostic signature in hepatocellular carcinoma

Zhang

Shi

Liu

et al. 2021

Molecular Therapy - Nucleic Acids

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Hepatocellular carcinoma (HCC) remains an extremely lethal disease worldwide. High-throughput methods have revealed global transcriptome dysregulation; however, a comprehensive investigation of the complexity and behavioral characteristics of the competing endogenous RNA (ceRNA) network in HCC is lacking. In this study, we extracted the transcriptome (RNA) sequencing data of 371 HCC patients from The Cancer Genome Atlas platform. With the comparison of the high Myc expression (Myc high ) tumor and low Myc expression (Myc low ) tumor groups in HCC, we identified 1,125 differentially expressed (DE) mRNAs, 589 long non-coding RNAs (lncRNAs), and 93 microRNAs (miRNAs). DE RNAs predicted the interactions necessary to construct an associated Myc ceRNA network, including 19 DE lncRNAs, 5 miRNAs, and 72 mRNAs. We identified a significant signature (long intergenic non-protein-coding [LINC] RNA 2691 [LINC02691] and LINC02499) that effectively predicted overall survival and had protective effects. The target genes of microRNA (miR)-212-3p predicted to intersect with DE mRNAs included SEC14-like protein 2 (SEC14L2) and solute carrier family 6 member 1 (SLC6A1), which were strongly correlated with survival and prognosis. With the use of the lncRNA-miRNA-mRNA axis, we constructed a ceRNA network containing four lncRNAs (LINC02691, LINC02499, LINC01354, and NAV2 antisense RNA 4), one miRNA (miR-212-3p), and two mRNAs (SEC14L2 and SLC6A1). Overall, we successfully constructed a mutually regulated ceRNA network and identified potential precision-targeted therapies and prognostic biomarkers.

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“…ENG (CD105), a transmembrane glycoprotein, is a transforming growth factor-β co-receptor [ 32 ]. ENG is involved in angiogenesis in solid tumors including HCC [ 33 ]. Several studies have shown that ENG downregulation in HCC tissue and its serum levels potentially serve as a poor prognostic marker in patients with HCC [ 32 , 34 , 35 ].…”

Section: Discussionmentioning

confidence: 99%

Circulating Exosomal MicroRNA-1307-5p as a Predictor for Metastasis in Patients with Hepatocellular Carcinoma

Eun

Seo

Baek

et al. 2020

Cancers

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Exosomal microRNAs (exo-miRs) contribute to cancer metastasis. To identify pro-metastatic circulating exo-miRs in hepatocellular carcinoma (HCC), next-generation sequencing-based plasma exo-miR profiles of 14 patients with HCC (eight non-metastatic and six with metastasis within 1 year of follow-up) were analyzed. Sixty-one miRs were significantly overexpressed among patients with metastatic HCC. Candidate miRs were selected through integrative analyses of two different public expression datasets, GSE67140 and The Cancer Genome Atlas liver hepatocellular carcinoma (TCGA_LIHC). Integrative analyses revealed 3 of 61 miRs (miR-106b-5p, miR-1307-5p, and miR-340-5p) commonly overexpressed both in metastasis and vascular invasion groups, with prognostic implications. Validation was performed using stored blood samples of 150 patients with HCC. Validation analysis showed that circulating exo-miR-1307-5p was significantly overexpressed in the metastasis group (p = 0.04), as well as in the vascular invasion and tumor recurrence groups. Circulating exo-miR-1307-5p expression was significantly correlated with tumor stage progression (p < 0.0001). Downstream signaling pathways of miR-1307 were predicted using TargetScan and Ingenuity Pathway Analysis. On comprehensive bioinformatics analysis, the downstream pathway of miR-1307-5p, promoting epithelial–mesenchymal transition (EMT), showed SEC14L2 and ENG downregulation. Our results show that circulating exo-miR-1307-5p promotes metastasis and helps predict metastasis in HCC, and SEC14L2 and ENG are target tumor suppressor genes of miR-1307 that promote EMT.

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Discovering master regulators in hepatocellular carcinoma: one novel MR, SEC14L2 inhibits cancer cells

Cited by 15 publications

References 56 publications

Identification of putative master regulators in rheumatoid arthritis synovial fibroblasts using gene expression data and network inference

Identification of putative master regulators in rheumatoid arthritis synovial fibroblasts using gene expression data and network inference

Construction of a Myc-associated ceRNA network reveals a prognostic signature in hepatocellular carcinoma

Circulating Exosomal MicroRNA-1307-5p as a Predictor for Metastasis in Patients with Hepatocellular Carcinoma

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