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Article Open Access

Identification of circular RNA biomarkers for Pien Tze Huang treatment of CCl4‑induced liver fibrosis using RNA‑sequencing

  • Authors:
    • Ting Wang
    • Jinhang Zhu
    • Longhui Gao
    • Muyun Wei
    • Di Zhang
    • Luan Chen
    • Hao Wu
    • Jingsong Ma
    • Lixing Li
    • Na Zhang
    • Yanjing Wang
    • Qinghe Xing
    • Lin He
    • Fei Hong
    • Shengying Qin
  • View Affiliations / Copyright

    Affiliations: Bio‑X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200030, P.R. China, Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, P.R. China, State Key Laboratory of Microbial Metabolism, Joint Laboratory of International Cooperation in Metabolic and Developmental Sciences, School of Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, P.R. China, Institutes of Biomedical Sciences and Children's Hospital, Fudan University, Shanghai 201102, P.R. China, Fujian Provincial Key Laboratory of Pien Tze Huang Natural Medicine Research and Development, Zhangzhou Pien Tze Huang Pharmaceutical Co., Ltd., Zhangzhou, Fujian 363000, P.R. China
    Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 309
    |
    Published online on: August 12, 2022
       https://doi.org/10.3892/mmr.2022.12825
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Abstract

Pien Tze Huang (PZH), a common hepatoprotective Traditional Chinese Medicine that has been found to be an effective treatment for carbon tetrachloride‑induced hepatic damage, including liver fibrosis. Circular RNAs (circRNAs) serve a crucial role in regulating gene expression levels via circRNA/micro (mi)RNA/mRNA networks in several human diseases and biological processes. However, whether circRNAs are involved in the underlying mechanism of the therapeutic effects of PZH on liver fibrosis remains unclear. Therefore, the aim of the present study was to investigate these effects using circRNA expression profiles from PZH‑treated fibrotic livers in model mice. A case‑control study on >59,476 circRNAs from CCl4‑induced (control group, n=6) and PZH‑treated (case group, n=6) mice was performed using circRNA sequencing in liver tissues. PZH treatment resulted in the differential expression of 91 circRNAs, including 58 upregulated and 33 downregulated circRNAs. Furthermore, the construction of competing endogenous networks also indicated that differentially expressed circRNAs acted as miRNA sponges. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of miRNA targets demonstrated that PZH‑affected circRNAs were mainly involved in biological processes such as ‘positive regulation of fibroblast proliferation’, ‘cellular response to interleukin‑1’ and ‘regulation of DNA‑templated transcription in response to stress’ and in a number of important pathways, such as ‘TNF signaling pathway’, ‘PI3K‑Akt signaling pathway’, ‘IL‑17 signaling pathway’ and ‘MAPK signaling pathway’. To further validate the bioinformatics data, reverse transcription‑­quantitative PCR was performed on seven miRNA targets in a human hepatic stellate LX‑2 cell model. The results suggested that seven of the miRNAs exhibited regulatory patterns that were consistent with those of the transcriptome sequencing results. Kaplan‑Meier survival analysis demonstrated that the expression levels of dihydrodiol dehydrogenase and solute carrier family 7, member 11 gene were significantly associated with patient survival, 269 patients with liver hepatocellular carcinoma from The Cancer Genome Atlas database. To the best of our knowledge, this was the first study to provide evidence that PZH affects circRNA expression levels, which may serve important roles in PZH‑treated fibrotic liver through the regulation of functional gene expression. In conclusion, the present study provided new insights into the mechanism underlying the pathogenesis of liver fibrosis and identified potential novel, efficient, therapeutic targets against liver injury.
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Copy and paste a formatted citation
Spandidos Publications style
Wang T, Zhu J, Gao L, Wei M, Zhang D, Chen L, Wu H, Ma J, Li L, Zhang N, Zhang N, et al: Identification of circular RNA biomarkers for Pien Tze Huang treatment of CCl4‑induced liver fibrosis using RNA‑sequencing. Mol Med Rep 26: 309, 2022.
APA
Wang, T., Zhu, J., Gao, L., Wei, M., Zhang, D., Chen, L. ... Qin, S. (2022). Identification of circular RNA biomarkers for Pien Tze Huang treatment of CCl4‑induced liver fibrosis using RNA‑sequencing. Molecular Medicine Reports, 26, 309. https://doi.org/10.3892/mmr.2022.12825
MLA
Wang, T., Zhu, J., Gao, L., Wei, M., Zhang, D., Chen, L., Wu, H., Ma, J., Li, L., Zhang, N., Wang, Y., Xing, Q., He, L., Hong, F., Qin, S."Identification of circular RNA biomarkers for Pien Tze Huang treatment of CCl4‑induced liver fibrosis using RNA‑sequencing". Molecular Medicine Reports 26.4 (2022): 309.
Chicago
Wang, T., Zhu, J., Gao, L., Wei, M., Zhang, D., Chen, L., Wu, H., Ma, J., Li, L., Zhang, N., Wang, Y., Xing, Q., He, L., Hong, F., Qin, S."Identification of circular RNA biomarkers for Pien Tze Huang treatment of CCl4‑induced liver fibrosis using RNA‑sequencing". Molecular Medicine Reports 26, no. 4 (2022): 309. https://doi.org/10.3892/mmr.2022.12825
Copy and paste a formatted citation
x
Spandidos Publications style
Wang T, Zhu J, Gao L, Wei M, Zhang D, Chen L, Wu H, Ma J, Li L, Zhang N, Zhang N, et al: Identification of circular RNA biomarkers for Pien Tze Huang treatment of CCl4‑induced liver fibrosis using RNA‑sequencing. Mol Med Rep 26: 309, 2022.
APA
Wang, T., Zhu, J., Gao, L., Wei, M., Zhang, D., Chen, L. ... Qin, S. (2022). Identification of circular RNA biomarkers for Pien Tze Huang treatment of CCl4‑induced liver fibrosis using RNA‑sequencing. Molecular Medicine Reports, 26, 309. https://doi.org/10.3892/mmr.2022.12825
MLA
Wang, T., Zhu, J., Gao, L., Wei, M., Zhang, D., Chen, L., Wu, H., Ma, J., Li, L., Zhang, N., Wang, Y., Xing, Q., He, L., Hong, F., Qin, S."Identification of circular RNA biomarkers for Pien Tze Huang treatment of CCl4‑induced liver fibrosis using RNA‑sequencing". Molecular Medicine Reports 26.4 (2022): 309.
Chicago
Wang, T., Zhu, J., Gao, L., Wei, M., Zhang, D., Chen, L., Wu, H., Ma, J., Li, L., Zhang, N., Wang, Y., Xing, Q., He, L., Hong, F., Qin, S."Identification of circular RNA biomarkers for Pien Tze Huang treatment of CCl4‑induced liver fibrosis using RNA‑sequencing". Molecular Medicine Reports 26, no. 4 (2022): 309. https://doi.org/10.3892/mmr.2022.12825
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