Competing endogenous RNA network and prognostic nomograms for hepatocellular carcinoma patients who underwent R0 resection

2019 ◽  
Vol 234 (11) ◽  
pp. 20342-20353 ◽  
Author(s):  
Yuntong Li ◽  
Bingfen Ma ◽  
Zhenyu Yin ◽  
Pingguo Liu ◽  
Jianming Liu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
R0 Resection ◽  
Competing Endogenous Rna ◽  
Competing Endogenous Rna Network

scholarly journals Competing endogenous RNA network: Potential entrants to gene editing in Hepatocellular Carcinoma Gene editing of ceRNA in Hepatocellular Carcinoma

2018 ◽  
Author(s):  
Ayman El-Sayed Shafei ◽  
Marwa Matboli ◽  
Mahmoud A. Ali ◽  
Ziad Nagy ◽  
Maged Reda ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Line ◽  
Hepg2 Cell ◽  
In Silico ◽  
Gene Editing ◽  
Hepg2 Cell Line ◽  
Competing Endogenous Rna ◽  
Competing Endogenous Rna Network ◽  
Synthetic Circuit ◽  
Polymerase Chain

AbstractBackgroundHepatocellular Carcinoma (HCC) is the leading cause of cancer deaths worldwide as well as in Egypt. We aimed to use Clustered Regulatory Interspaced Short Palindromic Repeats (CRISPR) gene editing technique to induce forced down-regulation of the circRNA which consequently modified miRNA expression in HepG2 cell line to prove the regulatory relationship between the RNA parts of an in silico-detected competing endogenous RNA network in HCCMethodWe first retrieved hsa_circ_0000064-miR-1285-TRIM2 mRNA from public microarray databases followed by in silico modelling to mimic the regulation kinetics of cirRNA associated ceRNA network. Secondly, we performed polymerase chain reaction (PCR)-based amplification of synthetic fragments, Gibson assembly of both CRISPR and non CRISPR based circuits, E-coli transformation, plasmid purification, HePG2 cell line transfection. Finally Expression levels of the chosen RNAs in hepatocellular carcinoma (HCC) cell line, HepG2, were examined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and the cytotoxic effect was validated by viability assay.TRIM2 protein expression was proved by immunohistochemistry and flowcytometry.ResultsInduction of hsa_circ_0000064 into HepG2 cell line via CRISPR-and non-CRISPR mediated synthetic circuit resulted in statistically significant decrease in cell number and, then, cellular viability with marked increase in hsa_circ_0000064 and TRIM2 mRNA levels and concomitant decrease in miR-1285 expression in HepG2 cell line compared with control (p<0.0). Moreover exogenous expression of hsa_circ_0000064 in HepG2 cell line showed increased expression of the tumor suppressor protein, TRIM2.ConclusionsOur integrative approach, including in silico data analysis and experimental validation proved that CRISPR-mediated synthetic circuit-based overexpression of hsa_circ_0000064 was more efficient than conventional transient transfection, representing a promising therapeutic strategy for HCC.Data AvailabilityOur Data was made available online on the IGEM wiki of team AFCM-EGYPT:http://2017.igem.org/Team:AFCM-Egypt. Synthetic parts have been submitted to IGEM Parts Registry.Financial DisclosureThe project was funded by Armed Forces College of Medicine AFCM, Zewail City of Science and Technology, National Research Center NRC, VitaBiotics, PHARCO Pharmaceuticals, Sim Era and DANUB Paintings. IDT provided 20 kb of DNA synthesis. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

scholarly journals Integrated analysis of competing endogenous RNA network revealing potential prognostic biomarkers of hepatocellular carcinoma

2019 ◽  
Vol 10 (14) ◽  
pp. 3267-3283 ◽  
Author(s):  
Xiwen Liao ◽  
Xiangkun Wang ◽  
Ketuan Huang ◽  
Chuangye Han ◽  
Jianlong Deng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Prognostic Biomarkers ◽  
Integrated Analysis ◽  
Competing Endogenous Rna ◽  
Competing Endogenous Rna Network

scholarly journals Comprehensive analyses of competing endogenous RNA networks reveal potential biomarkers for predicting hepatocellular carcinoma recurrence

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ping Yan ◽  
Zuotian Huang ◽  
Tong Mou ◽  
Yunhai Luo ◽  
Yanyao Liu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Malignant Tumors ◽  
Expression Profiles ◽  
Clinical Information ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
High Rate ◽  
Competing Endogenous Rna ◽  
Tissue Samples ◽  
Potential Biomarkers

Abstract Background Hepatocellular carcinoma (HCC) is one of the most common and deadly malignant tumors, with a high rate of recurrence worldwide. This study aimed to investigate the mechanism underlying the progression of HCC and to identify recurrence-related biomarkers. Methods We first analyzed 132 HCC patients with paired tumor and adjacent normal tissue samples from the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs). The expression profiles and clinical information of 372 HCC patients from The Cancer Genome Atlas (TCGA) database were next analyzed to further validate the DEGs, construct competing endogenous RNA (ceRNA) networks and discover the prognostic genes associated with recurrence. Finally, several recurrence-related genes were evaluated in two external cohorts, consisting of fifty-two and forty-nine HCC patients, respectively. Results With the comprehensive strategies of data mining, two potential interactive ceRNA networks were constructed based on the competitive relationships of the ceRNA hypothesis. The ‘upregulated’ ceRNA network consists of 6 upregulated lncRNAs, 3 downregulated miRNAs and 5 upregulated mRNAs, and the ‘downregulated’ network includes 4 downregulated lncRNAs, 12 upregulated miRNAs and 67 downregulated mRNAs. Survival analysis of the genes in the ceRNA networks demonstrated that 20 mRNAs were significantly associated with recurrence-free survival (RFS). Based on the prognostic mRNAs, a four-gene signature (ADH4, DNASE1L3, HGFAC and MELK) was established with the least absolute shrinkage and selection operator (LASSO) algorithm to predict the RFS of HCC patients, the performance of which was evaluated by receiver operating characteristic curves. The signature was also validated in two external cohort and displayed effective discrimination and prediction for the RFS of HCC patients. Conclusions In conclusion, the present study elucidated the underlying mechanisms of tumorigenesis and progression, provided two visualized ceRNA networks and successfully identified several potential biomarkers for HCC recurrence prediction and targeted therapies.

scholarly journals Downstaging and Resection of Initially Unresectable Hepatocellular Carcinoma with Tyrosine Kinase Inhibitor and Anti-PD-1 Antibody Combinations

Liver Cancer ◽  
2021 ◽  
pp. 1-10 ◽  
Author(s):  
Xiao-Dong Zhu ◽  
Cheng Huang ◽  
Ying-Hao Shen ◽  
Yuan Ji ◽  
Ning-Ling Ge ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Partial Response ◽  
Adverse Effects ◽  
Tyrosine Kinase ◽  
Stable Disease ◽  
Tumor Response ◽  
R0 Resection ◽  
Tumor Diameter ◽  
Remnant Liver ◽  
Unresectable Hepatocellular Carcinoma

<b><i>Background:</i></b> Combined therapy with tyrosine kinase inhibitors (TKIs) and anti-PD-1 antibodies has shown high tumor response rates for patients with unresectable hepatocellular carcinoma (HCC). However, using this treatment strategy to convert initially unresectable HCC to resectable HCC was not reported. <b><i>Methods:</i></b> Consecutive patients with unresectable HCC who received first-line therapy with combined TKI/anti-PD-1 antibodies were analyzed. Tumor response and resectability were evaluated via imaging every 2 months (±2 weeks) using RECIST v1.1. Resectability criteria were (1) R0 resection could be achieved with sufficient remnant liver volume and function; (2) intrahepatic lesions were evaluated as partial responses or stable disease for at least 2 months; (3) no severe or persistent adverse effects occurred; and (4) hepatectomy was not contraindicated. <b><i>Results:</i></b> Sixty-three consecutive patients were enrolled. Of them, 10 (15.9%) underwent R0 resection in 3.2 months (range: 2.4–8.3 months) after the initiation of combination therapy. At baseline, these 10 patients had a median largest tumor diameter of 9.3 cm, 7 had Barcelona Clinic Liver Cancer stage C (vascular invasion) disease, 2 had stage B, and 1 had stage A. Before surgery, 6 patients were evaluated as a partial response, 3 stable disease, and 1 partial response in the intrahepatic lesion but a new metastatic lesion in the right adrenal gland. Six patients (60%) achieved a pathological complete response. One patient died from immune-related adverse effects 2.4 months after hepatectomy. After a median follow-up of 11.2 months (range: 7.8–15.9 months) for other 9 patients, 8 survived without disease recurrence, and 1 experienced tumor recurrence. <b><i>Conclusions:</i></b> Combination of TKI/anti-PD-1 antibodies is a feasible conversion therapy for patients with unresectable HCC to become resectable. This study represents the largest patient cohort on downstaging role of combinational systemic therapy on TKI and PD-1 antibody for HCC.

scholarly journals The long noncoding RNA TUG1 acts as a competing endogenous RNA to regulate the Hedgehog pathway by targeting miR-132 in hepatocellular carcinoma

Oncotarget ◽  
2017 ◽  
Vol 8 (39) ◽  
pp. 65932-65945 ◽  
Author(s):  
Jingjing Li ◽  
Qinghui Zhang ◽  
Xiaoming Fan ◽  
Wenhui Mo ◽  
Weiqi Dai ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Hedgehog Pathway ◽  
Competing Endogenous Rna
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