CircRNA circBACH1 facilitates hepatitis B virus replication and hepatoma development by regulating the miR-200a-3p/MAP3K2 axis

• Na Du ^[1] ; Kailin Li ^[1] ; Yu Wang ^[1] ; Bo Song ^[1] ; Xuan Zhou ^[1] ; Shaoqiong Duan ^[1]
  1. [1] Suizhou Central Hospital Affiliated to Hubei Medical College, Suizhou, China
• Localización: Histology and histopathology: cellular and molecular biology, ISSN-e 1699-5848, ISSN 0213-3911, Vol. 37, Nº. 9, 2022, págs. 863-877
• Idioma: inglés
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• Resumen

  • Background. Hepatitis B virus (HBV) is a top contributor to hepatoma. Circular RNAs (circRNAs) have been elucidated to have a close connection with HBV-induced hepatoma. This study aimed to explore the role of circRNA BTB domain and CNC homolog 1 (circBACH1) in HBV replication and hepatoma progression, as well as the potential mechanistic pathway.

    Methods. Quantitative real-time polymerase chain reaction (qRT-PCR) assay was performed to assess the expression of circBACH1, microRNA (miR)-200a-3p, and mitogen-activated protein kinase kinase kinase 2 (MAP3K2). HBV replication was determined by enzyme-linked immunosorbent assay (ELISA) and qRTPCR assay. Cell viability and clonogenicity were detected via Cell Counting Kit-8 (CCK-8) assay and colony formation assay, respectively. Cell metastasis was examined by Transwell assay and wound healing assay.

    Annexing-V/PI staining was employed to monitor cell apoptosis using flow cytometry. Levels of MAP3K2, proliferation- and apoptosis-related proteins were analyzed by Western blotting. Target interaction between miR-200a-3p and circBACH1 or MAP3K2 was confirmed by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. The role of circBACH1 in vivo was investigated by xenograft model assay.

    Results. Expression of circBACH1 and MAP3K2 was increased, while miR-200a-3p expression was decreased in HCC tissues and HBV-transfected hepatoma cells. Depletion of circBACH1 or miR-200a3p overexpression impeded HBV replication, proliferation, and metastasis in HBV-transfected hepatoma cells. CircBACH1 was able to regulate MAP3K2 expression by sponging miR-200a-3p.

    CircBACH1 regulated HBV replication and hepatoma progression through the miR-200a-3p/MAP3K2 pathway. Moreover, circBACH1 deficiency hampered tumor growth in vivo.

    Conclusion. CircBACH1 knockdown had inhibitory effects on HBV replication and hepatoma progression, at least partly by modulating the miR-200a-3p/MAP3K2 axis.