HBx-induced miR-21 suppresses cell apoptosis in hepatocellular carcinoma by targeting interleukin-12

Ding, Yin; Wang, Yilang; Wang, Sai; Zhang, Liang; Miao, Yajun; Cao, Lili; Zhai, Xiaolu; Feng, Xiu; Yang, Li

doi:10.3892/or.2016.5026

Cited by 37 publications

(26 citation statements)

References 35 publications

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“…Some small RNAs could be induced or exploited by viruses to favor the viral infection and persistence by attenuating the immune response, ceasing cell apoptosis, and promoting cell growth [52][53][54]. Interestingly, this strategy, as employed by a virus, was observed in HSV-1 and its host interactions [55][56][57]. Based on the roles of miRNAs during HSV-1 infection, we presumed that circRNAs functioned as miRNA sponges to indirectly regulate the host transcriptional responses.…”

Section: Discussionmentioning

confidence: 99%

Deep RNA Sequencing Reveals a Repertoire of Human Fibroblast Circular RNAs Associated with Cellular Responses to Herpes Simplex Virus 1 Infection

Shi¹,

Hu²,

Mo³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Circular RNAs (circRNAs), a new class of regulators of gene expression, are involved in diverse physiological and pathogenic processes. However, their role in cellular responses to virus infection is yet unclear. Methods: A human lung fibroblast cell line was infected or mock infected by herpes simplex virus 1 (HSV-1). Deep RNA sequencing was used to profile the global changes in circRNAs, genes, and miRNAs following HSV-1 infection. Altered circRNAs, genes, and miRNAs were validated using quantitative reverse transcription polymerase chain reaction (RT-qPCR). An integration analysis of circRNAs, genes, and miRNAs was applied to investigate the putative function of the dysregulated circRNAs. Results: A total of 536 circRNAs, 3,885 genes, and 207 miRNAs were significantly dysregulated after HSV-1 infection. An integration analysis of circRNAs, genes, and miRNAs revealed the alleged involvement of dysregulated circRNAs in cellular responses to HSV-1 infection via the circRNA-miRNA-gene regulatory axis. These genes regulated by circRNAs were enriched to NOD-like receptor/JAK-STAT signaling pathway, and pathways of apoptosis, cell cycle progression, and cell death, all of which may be implicated in the viral pathogenesis and cellular immunity. Conclusions: These data present a comprehensive view for circRNAs induced by HSV-1 and their interplay with miRNAs and genes during HSV-1 infection, thus offering new insights into the mechanisms of interactions between HSV-1 and the host.

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Section: Discussionmentioning

confidence: 99%

Deep RNA Sequencing Reveals a Repertoire of Human Fibroblast Circular RNAs Associated with Cellular Responses to Herpes Simplex Virus 1 Infection

Shi¹,

Hu²,

Mo³

et al. 2018

Cell Physiol Biochem

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“…116 HBx-mediated miR-21 induction inhibited cell apoptosis by suppressing IL-12 and programmed cell death 4 (PDCD4), thereby promoting HCC. 117,118 miR-21-mediated PDCD4 repression indirectly activated AP-1, which increased miR-21 transcription, creating an miR-21-PDCD4-AP-1 positive feedback loop that enhances HCC migration and invasion. 119 CCL2, which is induced by myeloid-derived angiogenic endothelial progenitor cells, increased miR-21 levels through the CCR2/JNK/AP-1 signaling pathway, promoting HCC migration, invasion, and metastasis.…”

Section: Micrornas Regulate Hcc Development By Functioning As Inflammmentioning

confidence: 99%

Inflammation and Liver Cancer: Molecular Mechanisms and Therapeutic Targets

2019

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Hepatocellular carcinoma (HCC) is associated with chronic inflammation and fibrosis arising from different etiologies, including hepatitis B and C and alcoholic and nonalcoholic fatty liver diseases. The inflammatory cytokines tumor necrosis factor-α and interleukin-6 and their downstream targets nuclear factor kappa B (NF-κB), c-Jun N-terminal kinase (JNK), and signal transducer and activator of transcription 3 drive inflammation-associated HCC. Further, while adaptive immunity promotes immune surveillance to eradicate early HCC, adaptive immune cells, such as CD8+ T cells, Th17 cells, and B cells, can also stimulate HCC development. Thus, the role of the hepatic immune system in HCC development is a highly complex topic. This review highlights the role of cytokine signals, NF-κB, JNK, innate and adaptive immunity, and hepatic stellate cells in HCC and discusses whether these pathways could be therapeutic targets. The authors will also discuss cholangiocarcinoma and liver metastasis because biliary inflammation and tumor-associated stroma are essential for cholangiocarcinoma development and because primary tumor-derived inflammatory mediators promote the formation of a “premetastasis niche” in the liver.

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“…In addition, IL-12 reduces the probability of cancer development in CHB, which is a common cause of death in CHB. A study indicated that microRNA-21 could inhibit expression of IL-12, thereby increasing the proliferation of HCC (Yin et al, 2016). Another study demonstrated that genetic variants in IL-12 were associated with an increased risk of HBV-related HCC (Tan et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

The influence of therapeutic vaccine candidate against HBeAg pEGFP-N1-C (472-507)-ecdCD40L on dendritic cells

Zheng¹,

Xue²,

Zhang³

et al. 2018

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Hepatitis B virus (HBV) infection is a major public health problem and immune tolerance is responsible for persistent HBV infection. HBV therapeutic vaccines targeting HBV e antigen (HBeAg) may have an excellent effect in overcoming HBV immune tolerance. Thus, there is urgency for designing therapeutic vaccine candidates that target HBeAg. In this research, we fused the C (472-507) gene sequence of HBV with the extracellular domain of human CD40 ligand sequence and ligated this fused sequence into the pEGFP-N1 vector to construct the recombinant plasmid pEGFP-N1-C (472-507)-ecdCD40L. Then, the dendritic cells (DCs) generated from human peripheral blood were transfected with this recombinant plasmid. After this, the phenotype and function of DCs were assessed. Compared with the three control groups of pEGFP-N1-C (472-507), pEGFP-N1 and phosphate buffered saline (PBS), we found that DCs transfected with the recombinant plasmid pEGFP-N1-C (472-507)-ecdCD40L enhanced the expression of costimulatory molecules (CD80, CD86 and HLA-DR) and secretion of cytokine IL-12p70. Furthermore, the capacity of inducing the proliferation of allogeneic lymphocytes was also improved. Our study validated that transfecting DCs with recombinant plasmid pEGFP-N1-C (472-507)-ecdCD40L could activate DCs and enhance their functions. Therefore, C (472-507)-ecdCD40L fusion sequence may be a promising vaccine candidate for chronic hepatitis B therapythat targets HBeAg.

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HBx-induced miR-21 suppresses cell apoptosis in hepatocellular carcinoma by targeting interleukin-12

Cited by 37 publications

References 35 publications

Deep RNA Sequencing Reveals a Repertoire of Human Fibroblast Circular RNAs Associated with Cellular Responses to Herpes Simplex Virus 1 Infection

Deep RNA Sequencing Reveals a Repertoire of Human Fibroblast Circular RNAs Associated with Cellular Responses to Herpes Simplex Virus 1 Infection

Inflammation and Liver Cancer: Molecular Mechanisms and Therapeutic Targets

The influence of therapeutic vaccine candidate against HBeAg pEGFP-N1-C (472-507)-ecdCD40L on dendritic cells

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