HPV Oncoproteins and the Ubiquitin Proteasome System: A Signature of Malignancy?

Đukić, Anamaria; Lulić, Lucija; Thomas, Miranda; Skelin, Josipa; Saidu, Nathaniel Edward Bennett; Grce, Magdalena; Banks, Lawrence; Tomaić, Vjekoslav

doi:10.3390/pathogens9020133

Cited by 27 publications

(22 citation statements)

References 156 publications

(261 reference statements)

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“…16 Besides, human papillomavirus E6 and E7 interact with a broad spectrum of signaling pathways, including the mediation of cell cycle and the governance of apoptosis, which are of great importance in sustaining normal cell functions. 17 In the present study, we established that impairment of the CCNB1 function may offer a promising therapeutic option for treating CSCC by halting cell cycle progression and proliferation. Moreover, we proposed that FOXM1 directly bound to CCNB1 and recruited CBP/P300 to enhance the H3K27ac levels.…”

Section: Discussionmentioning

confidence: 56%

<p>CCNB1 Expedites the Progression of Cervical Squamous Cell Carcinoma via the Regulation by FOXM1</p>

Li¹,

Liu²,

Piao³

et al. 2020

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Background: Cervical squamous cell carcinoma (CSCC) is responsible for 80-85% of cervical cancer. Cyclin B1 (CCNB1) represents a hub gene during the development of cervical cancer. However, the oncogenic role of CCNB1 in CSCC remains unclear. Our study aims to explore the mechanism underlying CCNB1 regulation on cell cycle progression in CSCC cells. Methods: First, we analyzed differentially expressed genes from CSCC dataset GSE63678 and conducted gene function enrichment analysis. Subsequently, CCNB1 expression was knocked down in CSCC cell lines to assess cell proliferation, apoptosis, and cell cycle distribution. After the validation of the binding relationship between forkhead box protein M1 (FOXM1) and the promoter of CCNB1, the effect of FOXM1 on CCNB1 expression and on CSCC cell growth and apoptosis was verified. We further analyzed the histone ChIP-Seq data of CCNB1 in CSCC cells and measured the acetylation levels of the CCNB1 promoter histones. Results: CCNB1 was overexpressed in CSCC tissues and cells, and CCNB1 silencing inhibited the growth of CSCC cells, and promoted cell cycle arrest and apoptosis. FOXM1 potentiated CCNB1 transcription by binding to its promoter and recruiting CBP/P300, a histone acetyltransferase. Further increasing FOXM1 expression or increasing P300 activity in CSCC cells with CCNB1 knockdown elevated CCNB1 expression and proliferation and cell cycle progression of CSCC cells. Knockdown of CCNB1 activated the p53 pathway in cells. Conclusion: FOXM1 inhibited the activation of the p53 pathway by recruiting CBP/P300, which promoted the transcription of CCNB1, resulting in the growth and cell cycle progression of CSCC cells.

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Section: Discussionmentioning

confidence: 56%

<p>CCNB1 Expedites the Progression of Cervical Squamous Cell Carcinoma via the Regulation by FOXM1</p>

Li¹,

Liu²,

Piao³

et al. 2020

OTT

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“…Cervical cancer (CC), as one prevailing gynecological malignant tumor, ranks second among female malignancies following breast cancer, and even ranks first in some developing countries (1). Despite the employment of advanced radio-and chemo-therapy technologies, the prognosis of CC patients is still unsatisfactory because of regional recurrence and distant metastasis (2).…”

Section: Introductionmentioning

confidence: 99%

RETRACTED: LncRNA LIPE-AS1 Predicts Poor Survival of Cervical Cancer and Promotes Its Proliferation and Migration via Modulating miR-195-5p/MAPK Pathway

et al. 2021

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Aims: A growing number of studies have unveiled that long non-coding RNA (lncRNA) is conductive to cervical cancer (CC) development. However, the effect of LIPE-AS1 is remained to be studied in CC.Main Methods: Reverse transcription-polymerase chain reaction (RT-PCR) was employed to measure LIPE-AS1 expression in CC tissues and the adjacent normal tissues. Additionally, we conducted gain- and loss-of functional experiments of LIPE-AS1 and adopted CCK8 assay, BrdU assay, and in vivo tumor formation experiment to test the proliferation of CC cells (HCC94 and HeLa). Besides, the apoptosis, invasion, and epithelial-mesenchymal transformation (EMT) of CC cells were estimated using flow cytometry, transwell assay, and western blot, respectively. Further, LIPE-AS1 downstream targets were analyzed through bioinformatics, and the binding relationships between LIPE-AS1 and miR-195-5p were verified via dual-luciferase activity experiment and RNA Protein Immunoprecipitation (RIP) assay. Moreover, rescue experiments were conducted to confirm the effects of LIPE-AS1 and miR-195-5p in regulating CC development and the expressions of MAPK signaling pathway related proteins were detected by RT-PCR, western blot, and immunofluorescence.Key Findings: LIPE-AS1 was over-expressed in CC tissues (compared to normal adjacent tissues) and was notably related to tumor volume, distant metastasis. Overexpressing LIPE-AS1 accelerated CC cell proliferation, migration and EMT, inhibited apoptosis; while LIPE-AS1 knockdown had the opposite effects. The mechanism studies confirmed that LIPE-AS1 sponges miR-195-5p as a competitive endogenous RNA (ceRNA), which targets the 3′-untranslated region (3′-UTR) of MAP3K8. LIPE-AS1 promoted the expression of MAP3K8 and enhanced ERK1/2 phosphorylation, which were reversed by miR-195-5p.Significance: LIPE-AS1 regulates CC progression through the miR-195-5p/MAPK signaling pathway, providing new hope for CC diagnosis and treatment.

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“…IFN-I production is controlled at multiple layers to ensure appropriate mounting of antiviral and antitumor immune responses. It is clear that both host and viral ubiquitin systems play pivotal roles in IFN-I-mediated innate immunity and in cellular transformation mediated by oncogenic viruses represented by EBV (Epstein-Barr Virus), KSHV (Kaposi’s sarcoma-associated herpesvirus), and HPV (human papillomavirus) [ 36 , 37 , 38 , 39 , 40 , 41 ]. This review focuses on IFN-Is, and we summarize the current research on the TRIM family in modulating IFN-I-mediated innate immune response in antiviral and antitumor defense.…”

Section: Introductionmentioning

confidence: 99%

TRIMming Type I Interferon-Mediated Innate Immune Response in Antiviral and Antitumor Defense

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2021

Viruses

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The tripartite motif (TRIM) family comprises at least 80 members in humans, with most having ubiquitin or SUMO E3 ligase activity conferred by their N-terminal RING domain. TRIMs regulate a wide range of processes in ubiquitination- or sumoylation-dependent manners in most cases, and fewer as adaptors. Their roles in the regulation of viral infections, autophagy, cell cycle progression, DNA damage and other stress responses, and carcinogenesis are being increasingly appreciated, and their E3 ligase activities are attractive targets for developing specific immunotherapeutic strategies for immune diseases and cancers. Given their importance in antiviral immune response, viruses have evolved sophisticated immune escape strategies to subvert TRIM-mediated mechanisms. In this review, we focus on their regulation of IFN-I-mediated innate immune response, which plays key roles in antiviral and antitumor defense.

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HPV Oncoproteins and the Ubiquitin Proteasome System: A Signature of Malignancy?

Cited by 27 publications

References 156 publications

<p>CCNB1 Expedites the Progression of Cervical Squamous Cell Carcinoma via the Regulation by FOXM1</p>

<p>CCNB1 Expedites the Progression of Cervical Squamous Cell Carcinoma via the Regulation by FOXM1</p>

RETRACTED: LncRNA LIPE-AS1 Predicts Poor Survival of Cervical Cancer and Promotes Its Proliferation and Migration via Modulating miR-195-5p/MAPK Pathway

TRIMming Type I Interferon-Mediated Innate Immune Response in Antiviral and Antitumor Defense

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