Extended effects of human papillomavirus 16 E6-specific short hairpin RNA on cervical carcinoma cells

Li, Bai; Wei, Lanlan; Wang, Jianliu; Li, X.; He, Ping‐an

doi:10.1111/j.1525-1438.2006.00380.x

Cited by 16 publications

(20 citation statements)

References 36 publications

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“…4A). The findings were coherent with that reported previously for HPV-16 E6 effect on cell growth (1,8). In addition, the cell growth was increased from 67 to 88% of the control after the transfection of SiHa cells with HPV-16 E6 siRNA alone and together with DNMT1 cDNA (Fig.…”

Section: Dnmt1 Suppresses the Hpv-16 E6 Effect On Cell Growthsupporting

confidence: 82%

“…Cervical cancer is considered as a kind of viral cancer because persistent infection with human papillomavirus (HPV) is regarded as its most important risk factor. Although the infection of HPV does not necessarily cause cervical cancer, it is the prerequisite for its development (1)(2)(3).…”

Section: Introductionmentioning

confidence: 99%

“…In terms of cancer development, HPV-16 early proteins E6 and E7 are often believed to act as oncoproteins since both of the proteins are crucial for host cell immortalization and transformation (9). Particularly, E6 targets p53 tumor suppressor directly and enhances p53 degradation via the action of ubiquitin (1,9,10). The process of epigenetic silencing involves the methylation of specific CpG dinucleotides in the promoter region of the target gene.…”

Section: Introductionmentioning

confidence: 99%

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HPV-16 E6 upregulation of DNMT1 through repression of tumor suppressor p53

Yeung¹,

Tsang

et al. 2010

Oncol Rep

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Abstract. The HPV-16 early proteins E6 and E7 are considered to function as oncoproteins in cervical cancer. DNA methyltransferase 1 (DNMT1) is one of the enzymes involved in epigenetic silencing of tumor suppressor genes. In the present study, the functional role and regulation of DNMT1 in HPV-16 E6 associated cervical cancer development were examined. Knockdown of E6 in HPV-16 positive human cervical carcinoma SiHa and CaSki cells led to the increase in p53, repression of DNMT1 protein and promoter activity. Moreover, p53 knockdown increased the DNMT1 protein as well as promoter activity, indicating that p53 may mediate E6 upregulation of DNMT1. In addition, E6 knockdown induced growth retardation in SiHa cells, and the effect was partially reverted by DNMT1 overexpression. The results suggest that HPV-16 E6 may act through p53/ DNMT1 to regulate the development of cervical cancer.

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Section: Dnmt1 Suppresses the Hpv-16 E6 Effect On Cell Growthsupporting

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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HPV-16 E6 upregulation of DNMT1 through repression of tumor suppressor p53

Yeung¹,

Tsang

et al. 2010

Oncol Rep

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“…Among the promising gene approaches developed thus far to specifically target E6 and/or E7 (5), it was found that siRNA led to ablation of E6 in HPV18-positive HeLa cells leading to apoptosis, albeit under harsh conditions of cell transfection (7,10). Studies done with siE6 or short hairpin RNA showed that treated HeLa or SiHa cells did not die but stopped proliferating and became more sensitive to chemotherapy (9,22,32). This suggests that additional cell type -specific pathways probably need to be involved if therapeutic applications are to be achieved.…”

Section: Discussionmentioning

confidence: 99%

Suppression of cervical carcinoma cell growth by intracytoplasmic codelivery of anti-oncoprotein E6 antibody and small interfering RNA

Courtête¹,

Sibler²,

Zeder‐Lutz³

et al. 2007

Molecular Cancer Therapeutics

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Cervical cancer is caused by high-risk types of human papillomaviruses (HPV) that encode the E6 and E7 oncogenes. Silencing of E6 gene expression in HPVpositive cell lines by transfection of small interfering RNA (siRNA) with cationic lipids restores the dormant p53 tumor suppressor pathway. Because cationic lipids can also be used for intracytoplasmic delivery of proteins, we tested whether the delivery of monoclonal antibodies that bind to HPV16 E6 and neutralize its biological activity in vitro could restore p53 function in tumor cells. Here, we show that the 4C6 antibody is efficiently delivered into the cell cytoplasm using a lipidic reagent used for siRNA transfection. The delivery of 4C6 resulted in the nuclear accumulation of p53 protein in CaSki and SiHa cells but not in HeLa cells. Furthermore, the antibody-mediated p53 response was dramatically increased when a peptide corresponding to the 4C6 epitope and bearing a COOHterminal cysteine residue was added to the transduction mixture. We found that a fraction of the added peptides were dimers that allowed the formation of antibody polymers adsorbed onto the lipidic matrix. With this system, the proliferation of CaSki and SiHa cells was strongly diminished, but no apoptosis was detectable. Remarkably, cell growth was almost totally suppressed by the addition of E6-specific siRNA to the transduction complex. The results indicate that the activity of E6 oncoprotein can be down-regulated in vivo by lipidmediated antibody delivery and that antibodies and siRNA act synergistically when codelivered. This novel targeting strategy is simple to implement and may find therapeutic applications.

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“…Persistent infection with human papillomavirus (HPV) is regarded as its most important risk factor (Walboomers et al, 1999;Soliman et al, 2004;Bai et al, 2006). Infection with oncogenic high-risk subtypes of HPV may lead to cervical cancer (zur Hausen, 2002;Munoz et al, 2003) and over 50% of the cases are HPV-16 (Walboomers et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Human papillomavirus type 16 E6 induces cervical cancer cell migration through the p53/microRNA-23b/urokinase-type plasminogen activator pathway

et al. 2011

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Deregulation of microRNA (miRNA or miR) expression in human cervical cancer is associated frequently with human papillomavirus (HPV) integration. miR-23b is often downregulated in HPV-associated cervical cancer. Interestingly, urokinase-type plasminogen activator (uPA), the miR-23b target, is detected in cervical cancer, but not in normal cervical tissues. Thus, the importance of miR-23b and uPA in HPV-associated cervical cancer development is investigated. In this study, the high-risk subtype HPV-16 E6 oncoprotein was found to decrease the expression of miR-23b, increase the expression of uPA, and thus induce the migration of human cervical carcinoma SiHa and CaSki cells. uPA is the target gene for miR-23b as the miR repressed uPA expression and interacted with the 3 0 -untranslated region of uPA mRNA. The tumor suppressor p53 is known to be inactivated by HPV-16 E6. A consensus p53 binding site is detected in the promoter region of miR-23b, whereas p53 transactivated and also interacted with the miR's promoter. Therefore, p53 is believed to mediate the HPV-16 E6 downregulation of miR-23b. From the above, miR-23b/ uPA are confirmed to be involved in HPV-16 E6-associated cervical cancer development.

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Extended effects of human papillomavirus 16 E6-specific short hairpin RNA on cervical carcinoma cells

Cited by 16 publications

References 36 publications

HPV-16 E6 upregulation of DNMT1 through repression of tumor suppressor p53

HPV-16 E6 upregulation of DNMT1 through repression of tumor suppressor p53

Suppression of cervical carcinoma cell growth by intracytoplasmic codelivery of anti-oncoprotein E6 antibody and small interfering RNA

Human papillomavirus type 16 E6 induces cervical cancer cell migration through the p53/microRNA-23b/urokinase-type plasminogen activator pathway

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