Human papillomavirus E6 protein enriches the CD55(+) population in cervical cancer cells, promoting radioresistance and cancer aggressiveness

Leung, Thomas; Tang, Hermit Wai-Man; Siu, Michelle K.Y.; Chan, David; Chan, Ki; Cheung, Annie N.Y.; Ngan, Hextan Y.S.

doi:10.1002/path.4991

Cited by 28 publications

(27 citation statements)

References 42 publications

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“…Our previous report suggested that a cluster of differentiation (CD) marker, CD55, was upregulated in primary cervical cancer sphere cells. An enriched CD55 þ subpopulation was found in human papillomavirus (HPV)positive and HPV-E6-overexpressing clones that contributed to the aggressiveness of the cervical cancer cells (14). In this study, we identified CD71 as another potential cell surface marker that is also associated with the expression of the HPV-E6 protein.…”

Section: Introductionmentioning

confidence: 86%

“…For CRISPR/ Cas9 gene editing, SiHa cells were cotransfected with gRNA (GeneArt CRISPR U6 Strings DNA gRNA, Life Technologies) and Cas9 mRNA (GeneArt CRISPR Nuclease mRNA) using Lipofectamine 3000. The experimental procedures were performed as described previously (14). In addition, the potential off-targets were predicted using CRISPOR (http://crispor.org) and the Zhang Laboratory tool (MIT 2015; http://crispr.mit.edu/).…”

Section: Crispr Knockout Of the Cd71 Genementioning

confidence: 99%

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CD71+ Population Enriched by HPV-E6 Protein Promotes Cancer Aggressiveness and Radioresistance in Cervical Cancer Cells

Leung

Tang

Siu

et al. 2019

Molecular Cancer Research

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A subpopulation of cells within tumors has been suggested to possess the ability to initiate tumorigenesis and contribute to resistance to cancer therapy. Identification and isolation of this subpopulation in cancer cells can be achieved by detecting specific cell-surface markers. In this study, flow cytometry analysis revealed an abundant CD71 þ subpopulation in human papillomavirus (HPV)-positive cervical cancer cells, while limited CD71 þ cells were detected in HPV-negative cervical cancer cells. Furthermore, ectopic expression of the HPV-E6 protein in HPV-negative C33A cells enriched the CD71 þ subpopulation. The CD71 þ subpopulation isolated from the C33A cell line and an HPV-E6-overexpressing clone exhibited enhanced transforming ability, proliferation, and resistance to irradiation. In contrast, suppression of CD71 in HPV-positive SiHa cells and the HPV-E6-overexpressing stable clone inhibited spheroid formation and in vitro and in vivo tumorigenicity and sensitized cells to irradiation treatment. CRISPR/Cas9 knockout of CD71 in SiHa cells also produced similar inhibitory effects on tumorigenicity. Double knockout of CD71 and CD55 reversed the oncogenic properties of the HPV-E6-overexpressing clone. These findings suggest that the HPV-E6 protein enriches the subpopulation of CD71 þ cells in cervical cancer, which exhibit cancer stem-like cell properties and are resistant to irradiation treatment. Targeting the CD71 þ subpopulation in cervical cancer cells with siRNAs or CRISPR/ Cas9 may provide new insights for the development of novel therapeutic approaches for treating cervical cancer. Implications: We describe the enrichment of CD71 þ population by HPV-E6 protein in cervical cancer cells that promotes cancer aggressiveness and resistance to irradiation treatment.

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Section: Introductionmentioning

confidence: 86%

Section: Crispr Knockout Of the Cd71 Genementioning

confidence: 99%

CD71+ Population Enriched by HPV-E6 Protein Promotes Cancer Aggressiveness and Radioresistance in Cervical Cancer Cells

Leung

Tang

Siu

et al. 2019

Molecular Cancer Research

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“…We have demonstrated that CD55 is upregulated in spheroid cells derived from primary cervical cancer tissue and that these cells display a highly expressed 'dry' gene, suggesting that cervical cancer tissue may contain cells with CSC properties [37]. In recent years, mCRPs CD46, and CD55 have demonstrated that CD59 and CD59 are important factors in tumorigenesis in various types of tumors [38]. CRISPR / Cas9 targeting of CD55 may be able to completely abolish the oncogenic function of CD55 and enable radiation therapy of cervical cancer cells.…”

Section: Discussionmentioning

confidence: 99%

LncRNA sequencing analysis of cervical cancer identifies radiotherapy sensitivity markers

Zhang

Dong

et al. 2020

Preprint

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Background Cervical cancer is one of the most common human cancers worldwide. However, the treatment of cervical cancer does not meet patient expectations. In recent years, long noncoding RNAs (lncRNAs), which are nonprotein-coding transcripts, have been shown to play important roles in tumorigenesis and tumor progression. Methods The function and mechanism of lncRNAs in cervical carcinoma are still rarely reported. We selected 15 patients with cervical cancer and a good prognosis (RS) and 15 patients with cervical cancer and a poor prognosis (RR), and we then performed lncRNA Sequencing analysis to detect differentially expressed lncRNAs. Subsequently, we used online bioinformatics databases to explore the potential function of these dysregulated lncRNAs. Finally, quantitative real-time PCR was performed to confirm the expression levels of these dysregulated lncRNAs in sub-RR and RS samples. Results We used lncRNA Sequencing technology to reveal differentially expression between the lncRNA profiles of the RR and RS tissues, and we found 1097 upregulated and 1189 downregulated lncRNAs in cervical cancer (fold change > 2.0), 247 upregulated and 189 downregulated lncRNAs in cervical cancer (fold change > 5.0), and 94 upregulated and 95 downregulated lncRNAs in cervical cancer (fold change > 10.0). Conclusions This study provides a map of lncRNA expression in RR and RS tissues and provides a database for further study of the function and mechanisms of action of key lncRNAs in cervical cancer. LncRNA TCONS_00081487 regulate CD55 and increase the radiation sensitivity of cervical cancer.

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“…The viral and host (patient) gene expression profiles of the 20 HPV16‐positive RNA‐seq data further suggest that the E2 and E7 genes of HPV, but not E6, play a major role in HPV‐induced HNSCC. The molecular mechanism of HPV oncogenesis in HNSCC differs from what has been reported in cervical carcinogenesis (Leung et al ., ). The viral/host gene expression profiles of HPV‐induced HNSCC elucidate HPV oncogenesis in HNSCC.…”

Section: Introductionmentioning

confidence: 97%

Detection of human papillomavirus in cases of head and neck squamous cell carcinoma by RNA‐seq and VirTect

et al. 2019

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Next‐generation sequencing provides an opportunity to detect viral species from RNA‐seq data of human tissues, but existing computational approaches do not perform optimally on clinical samples. We developed a bioinformatic method called VirTect for detecting viruses in neoplastic human tissues using RNA‐seq data. Here, we used VirTect to analyze RNA‐seq data from 363 head and neck squamous cell carcinoma (HNSCC) patients and identified 22 human papillomavirus (HPV)‐induced HNSCCs. These predictions were validated by manual review of pathology reports on histopathologic specimens. VirTect showed better performance in recall and accuracy compared to the two existing prediction methods, VirusFinder and VirusSeq, in identifying viral sequences from RNA‐seq data. The majority of HPV carcinogenesis studies thus far have been performed on cervical cancer and generalized to HNSCC. Our results suggest that carcinogenesis of HPV‐induced HNSCC and other cases of HNSCC involve different genes, so understanding the underlying molecular mechanisms will have a significant impact on therapeutic approaches and outcomes. In summary, RNA‐seq together with VirTect can be an effective solution for the detection of viruses from tumor samples and can facilitate the clinicopathologic characterization of various types of cancers with broad applications for oncology.

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Human papillomavirus E6 protein enriches the CD55(+) population in cervical cancer cells, promoting radioresistance and cancer aggressiveness

Cited by 28 publications

References 42 publications

CD71+ Population Enriched by HPV-E6 Protein Promotes Cancer Aggressiveness and Radioresistance in Cervical Cancer Cells

CD71+ Population Enriched by HPV-E6 Protein Promotes Cancer Aggressiveness and Radioresistance in Cervical Cancer Cells

LncRNA sequencing analysis of cervical cancer identifies radiotherapy sensitivity markers

Detection of human papillomavirus in cases of head and neck squamous cell carcinoma by RNA‐seq and VirTect

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