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High throughput circRNA sequencing analysis reveals novel insights into the mechanism of nitidine chloride against hepatocellular carcinoma.

ABSTRACT: Nitidine chloride (NC) has been demonstrated to have an anticancer effect in hepatocellular carcinoma (HCC). However, the mechanism of action of NC against HCC remains largely unclear. In this study, three pairs of NC-treated and NC-untreated HCC xenograft tumour tissues were collected for circRNA sequencing analysis. In total, 297 circRNAs were differently expressed between the two groups, with 188 upregulated and 109 downregulated, among which hsa_circ_0088364 and hsa_circ_0090049 were validated by real-time quantitative polymerase chain reaction. The in vitro experiments showed that the two circRNAs inhibited the malignant biological behaviour of HCC, suggesting that they may play important roles in the development of HCC. To elucidate whether the two circRNAs function as "miRNA sponges" in HCC, we identified circRNA-miRNA and miRNA-mRNA interactions by using the CircInteractome and miRwalk, respectively. Subsequently, 857 miRNA-associated differently expressed genes in HCC were selected for weighted gene co-expression network analysis. Module Eigengene turquoise with 423 genes was found to be significantly related to the survival time, pathology grade and TNM stage of HCC patients. Gene functional enrichment analysis showed that the 423 genes mainly functioned in DNA replication- and cell cycle-related biological processes and signalling cascades. Eighteen hubgenes (SMARCD1, CBX1, HCFC1, RBM12B, RCC2, NUP205, ECT2, PRIM2, RBM28, COPS7B, PRRC2A, GPR107, ANKRD52, TUBA1B, ATXN7L3, FUS, MCM8 and RACGAP1) associated with clinical outcomes of HCC patients were then identified. These findings showed that the crosstalk between hsa_circ_0088364 and hsa_circ_0090049 and their competing mRNAs may play important roles in HCC, providing interesting clues into the potential of circRNAs as therapeutic targets of NC in HCC.

SUBMITTER: Xiong DD

PROVIDER: S-EPMC6737102 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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High throughput circRNA sequencing analysis reveals novel insights into the mechanism of nitidine chloride against hepatocellular carcinoma.

Xiong Dan-Dan DD Feng Zhen-Bo ZB Lai Ze-Feng ZF Qin Yue Y Liu Li-Min LM Fu Hao-Xuan HX He Rong-Quan RQ Wu Hua-Yu HY Dang Yi-Wu YW Chen Gang G Luo Dian-Zhong DZ

Cell death & disease 20190910 9

Nitidine chloride (NC) has been demonstrated to have an anticancer effect in hepatocellular carcinoma (HCC). However, the mechanism of action of NC against HCC remains largely unclear. In this study, three pairs of NC-treated and NC-untreated HCC xenograft tumour tissues were collected for circRNA sequencing analysis. In total, 297 circRNAs were differently expressed between the two groups, with 188 upregulated and 109 downregulated, among which hsa_circ_0088364 and hsa_circ_0090049 were validat ...[more]

PMID: 31506425

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Project description:Circular RNAs (circRNAs) are differentially expressed in various cancer types. The present study aimed to investigate the expression and clinical implication of circRNAs in hepatocellular carcinoma (HCC) and to evaluate the potential of circRNAs as diagnostic biomarkers for HCC. CircRNA expression was profiled in 19 patients with HCC and 19 normal controls using ribosomal RNA-depleted RNAs. Differentially expressed circRNAs (DE-circRNAs) between HCC and controls were identified using CIRI2 and distinct circRNA expression signatures were screened. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were used to predict the potential functions of these DE-circRNAs and the circRNA-miRNA-mRNA regulatory networks were then constructed. Several DE-circRNAs were selected and confirmed by RT-qPCR. A total of 40 DE-circRNAs (27 upregulated and 13 downregulated) were identified between patients with HCC and controls. Functional annotation indicated that these DE-circRNAs were involved in cellular components, molecular functions and cancer-associated pathways related to HCC. These included pathways in cancer, TNF signaling pathway, hepatitis B, hepatitis C and hepatocyte differentiation. The circRNA-miRNA-mRNA regulatory network was generated based on 11 candidate circRNAs. Receiver operating characteristic curve analysis indicated that Homo sapiens (hsa)_circ_0073239, hsa_circ_007090, hsa_circ_0008304, hsa_circ_0017586, hsa_circ_0000369 and hsa_circ_0001181 may serve as potential biomarkers for HCC. Results from Cell Counting Kit-8 assay suggested that small interfering RNA targeting hsa_circ_0001181 reduced the proliferation of HepG2 cells, which implicated it as a potential therapeutic target for HCC. Therefore, in the present study, the differential expression pattern and important role of circRNAs in HCC were determined. The present results highlight the diagnostic potential of circRNAs in HCC and provide novel insight into the development of and treatment approaches for HCC.

Dataset Information

High throughput circRNA sequencing analysis reveals novel insights into the mechanism of nitidine chloride against hepatocellular carcinoma.

Publications

High throughput circRNA sequencing analysis reveals novel insights into the mechanism of nitidine chloride against hepatocellular carcinoma.

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