Roles of E6 and E7 Human Papillomavirus Proteins in Molecular Pathogenesis of Cervical Cancer

Taghizadeh, Eskandar; Jahangiri, Sepideh; Rostami, Daryoush; Taheri, Forough; Renani, Pedram G.; Taghizadeh, Hassan; Hayat, Seyed Mohammad Gheibi

doi:10.2174/1389203720666190618101441

Cited by 20 publications

(19 citation statements)

References 100 publications

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“…E6 and E7 are highly expressed in HPV18-positive HeLa cells (30) and HPV16-and HPV18-positive ca Ski cells (31,32). E6 and E7, both encoded by HPV, play a critical role in the molecular pathogenesis of cervical cancer (6). High-risk HPV E6 and E7 are two viral oncoproteins that respectively, induce protein degradation of tumor suppressors p53 and pRb1 (37).…”

Section: Discussionmentioning

confidence: 99%

“…phase check point and then triggering abnormal chromosome replication. Suppressing the action of E6 and E7 is a key approach for cervical cancer therapy (6,18).…”

Section: Resveratrol Inhibits the Progression Of Cervical Cancer By Smentioning

confidence: 99%

“…The E region comprising E1-E8 encodes proteins essential for replication, transcription and transformation (5). E6 and E7 play a critical role in the molecular pathogenesis of cervical cancer (6). The expression level of HPV E6/E7 is closely related to the malignant degree of cervical cancer and the poor prognosis of patients (7,8).…”

Section: Introductionmentioning

confidence: 99%

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Resveratrol inhibits the progression of cervical cancer by suppressing the transcription and expression of HPV E6 and E7 genes

Sun

Xie

et al. 2020

Int J Mol Med

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Resveratrol is a representative polyphenol of diet-derived putative cancer chemopreventive agents, which have attracted increasing interest in the cancer chemoprevention community. The inhibition of the action of human papillomavirus (HPV) E6 and E7 has been considered a key approach for cervical cancer therapy. Resveratrol has been shown to induce the apoptosis, and reduce both the viability and mitotic index of a number of cancer cell lines, including human cervical cancer cells. In the present study, it was confirmed that resveratrol inhibited the HPV E6 mRNA, HPV E6 protein and phosphorylated retinoblastoma protein (p-pRb1) levels, and increased the p53 protein levels in HeLa and Ca Ski cells, as well as in subcutaneous tumor tissue grown from HeLa cells. High-risk HPV uses a bicistronic RNA to control E6 and E7 genes simultaneously. On the whole, the present study demonstrates that resveratrol inhibits cervical cancer development by suppressing the transcription and translation of E6 and E7, and also by promoting the apoptosis and G1/S phase transition arrest. These findings may provide the basis for the development of resveratrol as a candidate for cervical cancer therapy.

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Section: Discussionmentioning

confidence: 99%

“…phase check point and then triggering abnormal chromosome replication. Suppressing the action of E6 and E7 is a key approach for cervical cancer therapy (6,18).…”

Section: Resveratrol Inhibits the Progression Of Cervical Cancer By Smentioning

confidence: 99%

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Resveratrol inhibits the progression of cervical cancer by suppressing the transcription and expression of HPV E6 and E7 genes

Sun

Xie

et al. 2020

Int J Mol Med

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“…10 In addition to interfering with the p53 and Rb proteins, E6 and E7 also interfere with mammalian target of rapamycin (mTOR) signaling and senescence in the infected cells. 11,12 CIN grade 1 is considered a low-grade squamous intraepithelial lesion (LSIL), and the rate of spontaneous regression is 70-80%. 13 CIN grade 2 and CIN grade 3 are considered high-grade squamous intraepithelial lesions (HSIL).…”

Section: Introductionmentioning

confidence: 99%

<p>Therapeutic Vaccines for HPV-Associated Malignancies</p>

Rumfield

Roller

Pellom

et al. 2020

ITT

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Human papillomavirus (HPV)-related malignancies are responsible for almost all cases of cervical cancer in women, and over 50% of all cases of head and neck carcinoma. Worldwide, HPV-positive malignancies account for 4.5% of the global cancer burden, or over 600,000 cases per year. HPV infection is a pressing public health issue, as more than 80% of all individuals have been exposed to HPV by age 50, representing an important target for vaccine development to reduce the incidence of cancer and the economic cost of HPVrelated health issues. The approval of Gardasil ® as a prophylactic vaccine for high-risk HPV 16 and 18 and low-risk HPV6 and 11 for people aged 11-26 in 2006, and of Cervarix ® in 2009, revolutionized the field and has since reduced HPV infection in young populations. Unfortunately, prophylactic vaccination does not induce immunity in those with established HPV infections or HPV-induced neoplasms, and there are currently no therapeutic HPV vaccines approved by the US Food and Drug Administration. This comprehensive review will detail the progress made in the development of therapeutic vaccines against high-risk HPV types, and potential combinations with other immunotherapeutic agents for more efficient and rational designs of combination treatments for HPV-associated malignancies.

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“…Cervical cancer is the second leading cause of cancer deaths in women worldwide, and its clinical management remains a challenge [1]. Human papilloma virus (HPV) infection is the leading cause of cervical cancer, and HPV DNA is found in 70% of cervical cancers [2]. Expression of two HPV types (16 and 18) plays an essential role in cervical carcinogenesis through deregulating expression and activities of cell‐cycle‐related proteins, such as p16, retinoblastoma (RB) tumor suppressor protein, cyclin D1, p53, and ProEx C, which lead to unscheduled cell‐cycle activation and survival in HPV‐positive cervical cancer cells [3].…”

Section: Introductionmentioning

confidence: 99%

Abemaciclib sensitizes HPV‐negative cervical cancer to chemotherapy via specifically suppressing CDK4/6‐Rb‐E2F and mTOR pathways

Liu

Zhao

Fang

et al. 2020

Fundamemntal Clinical Pharma

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Cervical cancer is the second most common malignancy in women, and the novel therapeutic treatment is needed. Abemaciclib is a FDA‐approved drug for breast cancer treatment. In this work, we identified that abemaciclib has potent anti‐cervical cancer activity. We demonstrate that abemaciclib is the most effective drug against human papillomavirus (HPV)‐negative cervical cancer cells compared to ribociclib and palbociclib, with its IC50 at nanomolar concentration range. This is achieved by the inhibition of proliferation and induction of apoptosis, through specifically suppressing CDK4/6‐Rb‐E2F and mTOR pathways by abemaciclib in HPV‐negative cervical cancer cells. Of note, the combination of abemaciclib with paclitaxel and cisplatin at sublethal concentration results in much greater efficacy than chemotherapy alone. In addition, we confirm the efficacy of abemaciclib and its combination with paclitaxel or cisplatin at the doses that are not toxic to mice in HPV‐negative cervical cancer xenograft mouse model. Interestingly, we show that abemaciclib and other CDK4/6 inhibitors are not effective in targeting HPV‐positive cervical cancer cells, and this is likely to be associated with the high p16 and low Rb expression in HPV‐positive cervical cancer cells. Our work is the first to provide the preclinical evidence to demonstrate the potential of abemaciclib for the treatment of HPV‐negative cervical cancer. The mechanism analysis highlights the therapeutic value of inhibiting CDK4/6 in HPV‐negative but not HPV‐positive cervical cancer.

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Roles of E6 and E7 Human Papillomavirus Proteins in Molecular Pathogenesis of Cervical Cancer

Cited by 20 publications

References 100 publications

Resveratrol inhibits the progression of cervical cancer by suppressing the transcription and expression of HPV E6 and E7 genes

Resveratrol inhibits the progression of cervical cancer by suppressing the transcription and expression of HPV E6 and E7 genes

<p>Therapeutic Vaccines for HPV-Associated Malignancies</p>

Abemaciclib sensitizes HPV‐negative cervical cancer to chemotherapy via specifically suppressing CDK4/6‐Rb‐E2F and mTOR pathways

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