Hepatitis B Virus X Protein-Induced ROR<i>γ</i> Expression to Promote the Migration and Proliferation of Hepatocellular Carcinoma

Huang, Yu; Liang, Huasheng; He, Chuanxiong; Peng, Fang

doi:10.1155/2019/5407126

Cited by 8 publications

(5 citation statements)

References 33 publications

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“…Huang reported that RORc is highly expressed in liver tumor tissues, and its expression is closely associated with HBV infection, suggesting that RORc is an oncogene involved in the proliferation and migration of hepatocellular carcinoma. 18 Some reports also described RORc overexpression in lung cancer, breast cancer, and melanoma. As a subtype of RORc, RORct was reported to inhibit the development of colon cancer, 36 and RORct expression in colon cancer remains controversial.…”

Section: Discussionmentioning

confidence: 99%

“… 16 , 17 However, RORγ was identified as an oncogene in liver cancer, lung cancer, prostate cancer, gastric cancer, cervical cancer, and multiple myeloma. 18 – 22 Some researchers also indicated that RORγ could exert pro-tumor effects in breast cancer through regulating LC3, 15 , 23 suggesting that the function of RORγ varies among different cancers.…”

Section: Introductionmentioning

confidence: 99%

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Identification of RORγ as a favorable biomarker for colon cancer

Pan¹,

Li²,

Zhang³

et al. 2021

J Int Med Res

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Objective To evaluate the expression of retinoid-related orphan receptor gamma (RORγ) and its potential role in the prognosis of colon cancer. Methods The Cancer Genome Atlas and GSE117606 were used to evaluate to RORγ levels in colon cancer, and real-time quantitative polymerase chain reaction was applied for validation. UALCAN and MEXPRESS were used to analyze the associations of RORγ expression with clinical parameters. The survival analysis was conducted in GEPIA. Results RORγ expression was significantly lower in colon tumors than in adjacent normal mucosa tissues. RORγ expression was significantly associated with tumor stage, lymph node metastasis, and liver metastasis. The area under the curve for diagnosis was 0.71. Decreased RORγ expression was positively correlated with the incidence of lymphatic invasion, microsatellite instability, the presence of residual tumor, venous invasion, and copy number variation. Overall survival was longer in patients with higher RORγ expression, especially those with microsatellite instability-high features. Methylation analysis revealed that hypermethylation of the RORγ promoter was associated with the colon cancer stage. Conclusions RORγ downregulation could be a potential biomarker for colon cancer, especially for predicting prognosis. Decreased RORγ expression in colon tumor may be associated with promoter hypermethylation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Identification of RORγ as a favorable biomarker for colon cancer

Pan¹,

Li²,

Zhang³

et al. 2021

J Int Med Res

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“…RORγ overexpression is associated with promoter methylation and HBx protein. Furthermore, HBx-induced RORγ may facilitate the proliferation and migration of hepatoma cells[ 93 ], and RORα may be a possible diagnostic and prognostic biomarker for disease severity[ 94 ]. Overexpression of RORα , CRY2 , and PER1 is associated with a better survival of HCC patients, and regulating the circadian rhythm gene may help in the chronotherapy of such patients[ 94 ].…”

Section: Circadian Rhythmmentioning

confidence: 99%

“…Moreover, CLOCK and BMAL1 control transcription of the pattern recognition receptor, which is involved in nucleic acid detection during viral infections[ 104 ]. RORγ regulates the differentiation of Th17 cells, which secrete IL-17, an essential regulator of pro-inflammatory signaling[ 93 ]. REV-ERBα has a protective effect in various inflammatory processes[ 105 ].…”

Section: Circadian Rhythmmentioning

confidence: 99%

Hepatitis B and circadian rhythm of the liver

Škrlec¹,

Talapko²

2022

WJG

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The circadian rhythm in humans is determined by the central clock located in the hypothalamus’s suprachiasmatic nucleus, and it synchronizes the peripheral clocks in other tissues. Circadian clock genes and clock-controlled genes exist in almost all cell types. They have an essential role in many physiological processes, including lipid metabolism in the liver, regulation of the immune system, and the severity of infections. In addition, circadian rhythm genes can stimulate the immune response of host cells to virus infection. Hepatitis B virus (HBV) infection is the leading cause of liver disease and liver cancer globally. HBV infection depends on the host cell, and hepatocyte circadian rhythm genes are associated with HBV replication, survival, and spread. The core circadian rhythm proteins, REV-ERB and brain and muscle ARNTL-like protein 1, have a crucial role in HBV replication in hepatocytes. In addition to influencing the virus’s life cycle, the circadian rhythm also affects the pharmacokinetics and efficacy of antiviral vaccines. Therefore, it is vital to apply antiviral therapy at the appropriate time of day to reduce toxicity and improve the effectiveness of antiviral treatment. For these reasons, understanding the role of the circadian rhythm in the regulation of HBV infection and host responses to the virus provides us with a new perspective of the interplay of the circadian rhythm and anti-HBV therapy. Therefore, this review emphasizes the importance of the circadian rhythm in HBV infection and the optimization of antiviral treatment based on the circadian rhythm-dependent immune response.

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“…ROR expression is enhanced in HCC patients with HBV infection and overexpression of ROR in liver cancer cells can enhance their migration and proliferation in vitro (Y. Huang et al, 2019). Thus, we wanted to rule out a possible contribution of knocking out RORc expression in hepatocytes to the phenotype of IKK RORc KO mice.…”

Section: Intrahepatic Cholangiocarcinoma (Icca) Load Is Decreased In ...mentioning

confidence: 99%

RORc expressing immune cells negatively regulate tertiary lymphoid structure formation and support their pro-tumorigenic functions

Cinnamon

Stein

Zino

et al. 2022

Preprint

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Tertiary lymphoid structures (TLSs) are formed in many cancer types and have been correlated with better prognosis and response to immunotherapy. In liver cancer, TLSs have been reported to be pro-tumorigenic as they harbor tumor progenitor cells and nurture their growth. The processes involved in TLS development and acquisition of pro- or anti-tumorigenic phenotype in cancer are largely unknown. RORc expressing immune cells have been previously implicated in TLS formation, however we find that they are not necessary for TLS neogenesis in the liver under chronic inflammation conditions. On the contrary, RORc expressing cells rather negatively regulate TLS formation, since in their absence TLSs form in excess. Importantly, in chronically inflamed livers lacking RORc expressing cells, pro-tumorigenic TLSs become anti-tumorigenic, resulting in reduction of tumor load. Comparing liver pro- and anti-tumorigenic TLSs by transcriptional, proteomic and immunohistochemical analyses, revealed an enrichment of exhausted CD8 cells that retained effector functions and had a progenitor-like proliferative phenotype in anti-tumorigenic TLSs. Similar observations were found when comparing pro- and anti-tumorigenic TLSs in human tissues. Thus, RORc expressing cells negatively regulate CD8 cell abundance, and facilitate the pro-tumorigenic functions of hepatic TLSs.

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Hepatitis B Virus X Protein-Induced RORγ Expression to Promote the Migration and Proliferation of Hepatocellular Carcinoma

Cited by 8 publications

References 33 publications

Identification of RORγ as a favorable biomarker for colon cancer

Identification of RORγ as a favorable biomarker for colon cancer

Hepatitis B and circadian rhythm of the liver

RORc expressing immune cells negatively regulate tertiary lymphoid structure formation and support their pro-tumorigenic functions

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