Archives

  • 2018-07
  • 2019-04
  • 2019-05
  • 2019-06
  • 2019-07
  • 2019-08
  • 2019-09
  • 2019-10
  • 2019-11
  • 2019-12
  • 2020-01
  • 2020-02
  • 2020-03
  • 2020-04
  • 2020-05
  • 2020-06
  • 2020-07
  • 2020-08
  • 2020-09
  • 2020-10
  • 2020-11
  • 2020-12
  • 2021-01
  • 2021-02
  • 2021-03
  • 2021-04
  • 2021-05
  • 2021-06
  • 2021-07
  • 2021-08
  • 2021-09
  • 2021-10
  • 2021-11
  • 2021-12
  • 2022-01
  • 2022-02
  • 2022-03
  • 2022-04
  • 2022-05
  • 2022-06
  • 2022-07
  • 2022-08
  • 2022-09
  • 2022-10
  • 2022-11
  • 2022-12
  • 2023-01
  • 2023-02
  • 2023-03
  • 2023-04
  • 2023-05
  • 2023-06
  • 2023-07
  • 2023-08
  • 2023-09
  • 2023-10
  • 2023-11
  • 2023-12
  • 2024-01
  • 2024-02
  • 2024-03
  • HCC is one of the

    2022-07-01

    HCC is one of the most prevalent malignant tumors and a leading cause of cancer-related death, globally [[11], [12], [13]]. Hepatitis B virus (HBV) infection is closely related to the development of liver diseases [[14], [15], [16], [17]]. More than 350 million people are chronically infected with HBV worldwide, and of these, about one-third develop severe HBV-related complications [[18], [19], [20]]. Upon HBV infection, cccDNA, which harbors a chromatin-like structure, dwells in the nuclei of infected cells. There, cccDNA serves as a template for the transcription of all viral RNAs, and thus, it sustains viral persistence [[21], [22], [23]]. The DNA cytidine deaminases, APOBEC3A (termed A3A) and APOBEC3B (termed A3B), are responsible for the deamination (i.e., destruction) of HBV cccDNA [24,25]. The interactions between HBV and host factors play crucial roles in the development of HCC [26]. However, the effect of lncRNAs on HBV is unclear.
    Material and methods
    Results
    Discussion HULC was the first identified lncRNA that was specifically overexpressed in liver cancer [7]. We previously reported that HULC played pivotal roles in aberrant lipid metabolism and tumor angiogenesis in HCC [8,10]. The interplay between HBV and host factor plays vital roles in the development of hepatoma. However, the significance of HULC in HBV-related HCC is poorly understood. In this study, we investigated the mechanism underlying the HULC enhancement of hepatocarcinogenesis in HBV-related-HCC. We first observed that HULC could activate HBV replication in hepatoma cells. It has been known that the Anti-Inflammatory Peptide 1 deaminization activity of APOBEC3A or APOBEC3B is essential for inducing cccDNA degradation [24]. Strikingly, we demonstrated that HULC was able to maintain the stability of HBV cccDNA by down-regulating APOBEC3B. We showed that HULC increased miR-539 -expression, which targeted the APOBEC3B mRNA 3′UTR. It was previously reported that HULC might act as an endogenous sponge, which down-regulated the miR-372 and miR-107 [8,9]. Moreover, our previous data showed that HULC suppressed the miR-9 by inducing CpG island methylation of the miR-9 promoter [10]. It has been reported that HBx constitutively enhances tyrosine phosphorylation on STAT3 [32]. Here, our data revealed that HULC elevated HBx, which transcriptionally co-activated STAT3 to activate the miR-539 promoter. Functionally, we demonstrated that HULC could activate HBV replication by HBx/miR-539/APOBEC3B signaling, leading to the growth of hepatoma cell in vitro and in vivo. To better understand the effect of HBV on gene expression, we profiled HBV-modulated genes with cDNA microarrays. Our data showed that HBV globally affected cellular gene expression. HBV is known to be a key driver in hepatocarcinogenesis. However, the deletion of APOBEC3B might promote persistent HBV infection, and therefore, increases the risk of developing HCC [25]. In this study, we found that APOBEC3B reduced the growth of HBV-expressing hepatoma cells in vitro and in vivo. It suggests that APOBEC3B may serve as a potential tumor suppressor in HBV-related HCC. Thus, we conclude that HULC is able to activate HBV by HBx/STAT3/miR-539/APOBEC3B signaling in HBV-related HCC. Previous studies showed that antiviral treatments for viral hepatitis appeared to reduce the risk of HCC in patients chronically infected with HBV [34,35]. In this study, we failed to observe that ETV and LdT could affect the expression of HULC, miR-539 or APOBEC3B in HBV-expressing hepatoma cells. It implies that no-response to the HULC/miR-539/APOBEC3B signaling might contribute to the failure of nucleos(t)ide analogues in eliminating HBV. Therapeutically, HULC may serve as a therapeutic target for HCC. However, the detailed mechanism by which HULC modulates HBV cccDNA is not well documented, largely due to the lack of animal models that reproduce clinical HBV-associated HCC. Overall, our finding suggests that the interaction between host factors and HBV plays a crucial role in hepatocarcinogenesis.