HPV16 early gene E5 specifically reduces miRNA-196a in cervical cancer cells

Liu, Chanzhen; Lin, Jianfei; Li, Lianqin; Zhang, Yonggang; Chen, Weiling; Cao, Zijian; Zuo, Huancong; Chen, Chunling; Kee, Kehkooi

doi:10.1038/srep07653

Cited by 29 publications

(21 citation statements)

References 53 publications

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“…Cervical cancer (CC) has a high death rate and is the third most common type of cancer worldwide [ 1 ]. It is estimated that over 529,000 people are diagnosed with cervical cancer every year, with most cases occurring in developing countries.…”

Section: Introductionmentioning

confidence: 99%

Overexpression of microRNA-132 enhances the radiosensitivity of cervical cancer cells by down-regulating Bmi-1

Zhang

Cao

et al. 2017

Oncotarget

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We examined the effects of microRNA-132 (miR-132) on Bmi-1 expression and radiosensitivity in HeLa, SiHa, and C33A cervical cancer (CC) cells and 104 CC patients. MiR-132 expression was decreased and Bmi-1 expression was increased in tumor tissues compared to adjacent normal tissues and in radiotherapy-resistant patients compared to radiotherapy-sensitive patients. MiR-132 expression and Bmi-1 mRNA expression were also negatively correlated in tumor tissues. HeLa, SiHa, and C33A cells were divided into blank, miR-132 negative control (NC), miR-132 inhibitor, miR-132 mimics, siBmi-1, and miR-132 inhibitor + siBmi-1 groups, after which expression of miR-132 and Bmi-1, and the interaction between them and cell survival, proliferation, and apoptosis were examined. Bmi-1 was confirmed as a target of miRNA-132. Survival was higher and apoptosis lower in the miR-132 inhibitor group than the blank group after various doses of radiation. By contrast, survival was lower and apoptosis higher in the miRNA-132 mimics and siBmi-1 groups than in the blank group. Moreover, miR-132 expression increased and Bmi-1 mRNA expression decreased in each group at radiation doses of 6 and 8 Gy. Finally, co-administration of radiotherapy and exogenous miR-132 inhibited the growth of HeLa cell transplant-induced tumors in nude mice more effectively than radiotherapy alone. These results suggest overexpression of miR-132 enhances the radiosensitivity of CC cells by down-regulating Bmi-1 and that miR-132 may be a useful new target for the treatment of CC.

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Section: Introductionmentioning

confidence: 99%

Overexpression of microRNA-132 enhances the radiosensitivity of cervical cancer cells by down-regulating Bmi-1

Zhang

Cao

et al. 2017

Oncotarget

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“…To evaluate the efficacy of Z HPV16 E7 affitoxin384, cell viability assay was performed with CCK-8 kit (Dojindo) as described in a previous study with minor modifications 30 . Briefly, SiHa, CaSki, HeLa and A375 cells were plated onto a 96-well plate at 1×10 4 cells per well, followed by treatment with Z HPV16 E7 affitoxin384 at different concentrations (0.1, 0.25, 0.5, 1.0 and 2.0 μM).…”

Section: Methodsmentioning

confidence: 99%

A novel HPV16 E7-affitoxin for targeted therapy of HPV16-induced human cervical cancer

et al. 2018

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Cervical cancer, the second most common cause of cancer death in women worldwide, is significantly associated with infection of high-risk human papillomaviruses (HPVs), especially the most common genotype, HPV 16. To date, there is no established noninvasive therapy to treat cervical cancer.Methods: Here, we report a novel affitoxin that targets HPV16 E7 protein, one of the primary target proteins in molecular targeted therapy for HPV-induced cervical cancer. The affitoxin, ZHPV16E7 affitoxin384 was generated by fusing the modified Pseudomonas Exotoxin A (PE38KDEL) to the HPV16 E7-specific affibody. The expressed and purified ZHPV16E7 affitoxin384 was characterized using numerous methods. SPR assay, indirect immunofluorescence assay, and near-infrared (NIR) optical imaging were respectively performed to assess the targeting ability of ZHPV16E7 affitoxin384 to HPV16 E7 protein both in vitro and in vivo. Cell viability assays and SiHa tumor-bearing nude mice were used to evaluate the efficacy of ZHPV16 E7 affitoxin384 in vitro and in vivo, respectively.Results: Using in vitro methods the SPR assay and indirect immunofluorescence assay showed that ZHPV16E7 affitoxin384 targeted HPV16 E7 with high binding affinity and specificity. Significant reduction of cell viability in HPV16 positive cells was observed in the presence of ZHPV16 E7 affitoxin384. By NIR optical imaging, ZHPV16 E7 affitoxin384 specifically targeted HPV16 positive tumors in vivo. ZHPV16E7 affitoxin384 showed significant in vivo antitumor efficacy in two kinds of tumor-bearing nude mouse models.Conclusions: ZHPV16E7 affitoxin384 is a potent anti-cervical cancer therapeutic agent that could be effective against HPV16 positive tumors in humans.

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“…It has been suggested that HPV16 E5 specifically down-regulates miR196a upon infection of the human cervix facilitating the transformation of normal cervix cells to cervical carcinoma. 68,69 Further, miR-34a showed also a reduced expression occurring in an early-onset event in the development of HPV associated cervical cancer. The oncoprotein E6 was suggested to reduce miR-34a expression in the p53-dependent pathway during precancerous lesions, although the exact mechanisms remain unclear.…”

Section: Cervical Cancer and Mirnasmentioning

confidence: 99%

HPV epigenetic mechanisms related to Oropharyngeal and Cervix cancers

Domenico

Giovane

Kouidhi

et al. 2018

Cancer Biology & Therapy

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Human Papilloma Virus infection is very frequent in humans and is mainly transmitted sexually. The majority of infections are transient and asymptomatic, however, if the infection persists, it can occur with a variety of injuries to skin and mucous membranes, depending on the type of HPV involved. Some types of HPV are classified as high oncogenic risk as associated with the onset of cancer. The tumors most commonly associated with HPV are cervical and oropharyngeal cancer, epigenetic mechanisms related to HPV infection include methylation changes to host and viral DNA and chromatin modification in host species. This review is focused about epigenethic mechanism, such as MiRNAs expression, related to cervix and oral cancer. Specifically it discuss about molecular markers associated to a more aggressive phenotype. In this way we will analyze genes involved in meiotic sinaptonemal complex, transcriptional factors, of orthokeratins, sinaptogirin, they are all expressed in cancer in a way not more dependent on cell differentiation but HPV-dependent.

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HPV16 early gene E5 specifically reduces miRNA-196a in cervical cancer cells

Cited by 29 publications

References 53 publications

Overexpression of microRNA-132 enhances the radiosensitivity of cervical cancer cells by down-regulating Bmi-1

Overexpression of microRNA-132 enhances the radiosensitivity of cervical cancer cells by down-regulating Bmi-1

A novel HPV16 E7-affitoxin for targeted therapy of HPV16-induced human cervical cancer

HPV epigenetic mechanisms related to Oropharyngeal and Cervix cancers

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