The oncogenic role of HBXIP

Xiu, Mengxi; Zeng, Xiaohong; Shan, Renfeng; Wen, Wu; Li, Jianfeng; Wan, Renhua

doi:10.1016/j.biopha.2020.111045

Cited by 13 publications

(16 citation statements)

References 64 publications

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“…Several mechanisms have been proposed to account for HBXIP’s oncogenic roles. Among these mechanisms, metabolism reprogramming has been validated to be associated with METTL3 in HCC ( Yang N. et al, 2020 ; Xiu et al, 2021 ). Liver cancer cells is metabolically characterized by the Warburg effect (or aerobic glycolysis), with enhanced glycolysis and increased level of lactic acid ( Koppenol et al, 2011 ; Vaupel et al, 2019 ).…”

Section: Mechanisms Underlying the Carcinogenesis And Progression Of Hccmentioning

confidence: 99%

The Role of RNA Methyltransferase METTL3 in Hepatocellular Carcinoma: Results and Perspectives

Fan

Lin

Hao

et al. 2021

Front. Cell Dev. Biol.

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Hepatocellular carcinoma (HCC) is the 6th most prevalent cancer and the 4th leading cause of cancer-related death worldwide. Mechanisms explaining the carcinogenesis of HCC are not clear yet. In recent years, rapid development of N6-methyladenosine (m6A) modification provides a fresh approach to disclosing this mystery. As the most prevalent mRNA modification in eukaryotes, m6A modification is capable to post-transcriptionally affect RNA splicing, stability, and translation, thus participating in a variety of biological and pathological processes including cell proliferation, apoptosis, tumor invasion and metastasis. METTL3 has been recognized as a pivotal methyltransferase and essential to the performance of m6A modification. METTL3 can regulate RNA expression in a m6A-dependent manner and contribute to the carcinogenesis, tumor progression, and drug resistance of HCC. In the present review, we are going to make a clear summary of the known roles of METTL3 in HCC, and explicitly narrate the potential mechanisms for these roles.

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Section: Mechanisms Underlying the Carcinogenesis And Progression Of Hccmentioning

confidence: 99%

The Role of RNA Methyltransferase METTL3 in Hepatocellular Carcinoma: Results and Perspectives

Fan

Lin

Hao

et al. 2021

Front. Cell Dev. Biol.

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“…5 and Supplementary Fig. 1K ) and reinforce their respective tumor-promoting actions 32 , 33 . Therefore, simultaneous inhibition of HBXIP/Nrf2 is a promising therapeutic approach to enhance the efficacy of breast cancer chemo-/radiotherapy.…”

Section: Discussionmentioning

confidence: 56%

HBXIP induces anoikis resistance by forming a reciprocal feedback loop with Nrf2 to maintain redox homeostasis and stabilize Prdx1 in breast cancer

Zhou

Guo

et al. 2022

npj Breast Cancer

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Anoikis resistance is an essential prerequisite for tumor metastasis, but the underlying molecular mechanisms remain unknown. Herein, we report that the oncoprotein hepatitis B X-interacting protein (HBXIP) is prominently upregulated in breast cancer cells following ECM detachment. Altering HBXIP expression can impair the anchorage-independent growth ability of tumor cells. Mechanistically, HBXIP, which binds to Kelch-like ECH-associated protein 1 (Keap1) to activate nuclear factor E2-related factor 2 (Nrf2), contains a cis-acting antioxidant response element (ARE) in the gene promoter and is a target gene of Nrf2. The HBXIP/Nrf2 axis forms a reciprocal positive feedback loop that reinforces the expression and tumor-promoting actions of each protein. In response to ECM detachment, Nrf2 reduces reactive oxygen species (ROS) accumulation, protects the mitochondrial membrane potential and increases cellular ATP, GSH and NADPH levels to maintain breast cancer cell survival. Meanwhile, the reinforcement of HBXIP induced by Nrf2 inhibits JNK1 activation by inhibiting ubiquitin-mediated degradation of Prdx1, which also plays an essential role in promoting ECM-detached cell survival. Furthermore, a strong positive correlation was identified between HBXIP expression and Prdx1 expression in clinical breast cancer tissues and TCGA Pan-Cancer Atlas clinical data of breast invasive carcinoma based on the cBioPortal cancer genomics database. Co-expression of HBXIP and Prdx1 predicts a poor prognosis for breast cancer patients. Collectively, our findings reveal a significant mechanism by which the HBXIP/Nrf2 feedback loop contributes to anoikis resistance by maintaining redox homeostasis and inhibiting JNK1 activation and support the likely therapeutic value of the HBXIP/Nrf2 axis in breast cancer patients.

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“…HBsAg positive patients with cancer, including nasopharyngeal carcinoma [12], lung cancer [13], breast cancer [14], ovarian cancer [15], diffuse large B cell lymphoma [16][17][18], and pancreatic cancer [19] have an inferior OS. Previous studies speculated that it may be linked to certain types of immunological dysfunction [20] HBV reactivation [21], or the presence of Hepatitis B X-interacting protein [22]. Given that HBV can be transmitted by sexual contact, it is plausible that HBV may be present in the epithelium of the cervix and promote the progression of cervical cancer.…”

Section: Discussionmentioning

confidence: 99%

“…Current or past HBV infection was shown to be an adverse prognostic Ivyspring International Publisher factor in patients with nasopharyngeal carcinoma [12], lung cancer [13], breast cancer [14], ovarian cancer [15], diffuse large B cell lymphoma [16][17][18], and pancreatic cancer [19]. The latent mechanism leading to the unfavorable prognosis in HBV-infected patients with malignancies may be linked to certain types of immunological dysfunction [20], HBV reaction [21] or the presence of Hepatitis B X-interacting protein, which plays an oncogenic role in cancer progression [22]. Given that HBV can be transmitted by sexual contact, it is plausible that HBV may interact with human papillomavirus to promote the development and progression of cervical cancer.…”

Section: Introductionmentioning

confidence: 99%

Prognostic value of serological markers of hepatitis B virus infection in squamous cell cervical cancer

Wu¹,

Li²,

Li³

et al. 2021

J. Cancer

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Objective: The current study aimed to investigate the prognostic value of serological markers of hepatitis B virus (HBV) infection in squamous cell cervical cancer. Methods: Squamous cell cervical cancer patients treated by concurrent chemoradiotherapy from January 2013 to December 2015 at Yunnan Cancer Hospital were retrospectively reviewed. Results: Of a total of 277 patients, 12 (4.33%), 93 (33.57%), 2 (0.72%), 25 (9.02%), and 36 patients (13.00%) were seropositive for hepatitis B surface antigen (HBsAg), anti-hepatitis B surface antibodies (anti-HBs), hepatitis B envelope antigen (HBeAg), anti-hepatitis B envelope antibodies (anti-HBe), and anti-hepatitis B core antibodies (anti-HBc), respectively. No patients experienced more than mild hepatic adverse events during treatment. The five-year overall survival (OS) rates for patients with anti-HBs positive or negative status were 85.8% and 66.2% (p = 0.039), respectively. No statistically significant difference in the five-year OS rates was observed in HBsAg positive and negative, HBeAg positive and negative, anti-HBe positive and negative, anti-HBc positive and negative patients. The multivariable analysis revealed that anti-HBs positivity was an independent favorable prognostic factor for OS (HR= 0.279; 95%CI: 0.083-0.936; p = 0.039) in patients younger than 50 years. Conclusions: The presence of anti-HBs predicts a superior OS for squamous cell cervical cancer patients aged younger than 50 years.

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The oncogenic role of HBXIP

Cited by 13 publications

References 64 publications

The Role of RNA Methyltransferase METTL3 in Hepatocellular Carcinoma: Results and Perspectives

The Role of RNA Methyltransferase METTL3 in Hepatocellular Carcinoma: Results and Perspectives

HBXIP induces anoikis resistance by forming a reciprocal feedback loop with Nrf2 to maintain redox homeostasis and stabilize Prdx1 in breast cancer

Prognostic value of serological markers of hepatitis B virus infection in squamous cell cervical cancer

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