HPV: Molecular pathways and targets

Gupta, Shilpi; Kumar, Prabhat; Das, Bhudev C.

doi:10.1016/j.currproblcancer.2018.03.003

Cited by 136 publications

(130 citation statements)

References 86 publications

Supporting

Mentioning

115

Contrasting

Unclassified

Order By: Relevance

“…Even though E1, E2, L1 and L2 are always encountered in all HPVs, the other genes may vary (Stubenrauch et al, 2007;Nobre et al, 2009). The major oncogenes are considered to be E5, E6 and E7, which are also known for altering a variety of signaling pathways, such as Wnt, Notch, PI3K/Akt, MAPK, IFN and NF-κB and others (Gupta et al, 2018;Xu et al, 2018;Wang and Chen, 2019). However, studies have demonstrated that the HPV infection could alter the interaction between miRNAs and some of these pathways.…”

Section: Microrna Signaling In Hpv Infectionmentioning

confidence: 99%

MicroRNA Involvement in Signaling Pathways During Viral Infection

Barbu

Condrat

Thompson

et al. 2020

Front. Cell Dev. Biol.

115

View full text Add to dashboard Cite

Section: Microrna Signaling In Hpv Infectionmentioning

confidence: 99%

MicroRNA Involvement in Signaling Pathways During Viral Infection

Barbu

Condrat

Thompson

et al. 2020

Front. Cell Dev. Biol.

115

View full text Add to dashboard Cite

“…However, the molecular mechanism underlying EMT remains complex, and a series of signaling molecules regulating EMT has been identified, including TGF-β, ERK/p-ERK, MAPK/p-MAPK, AKT/p-AKT, Smad/p-Smad, Notch and WNT/β-catenin [22,23]. In recent years, the WNT/βcatenin pathway has gradually gained attention in HR-HPV induced cervical cancer [24][25][26]. The classical cadherin family is comprised of various proteins, including E-cadherin, Ncadherin and P-cadherin, all of which are required for normal cell-cell adhesion.…”

Section: Discussionmentioning

confidence: 99%

WNT1, a target of miR-34a, promotes cervical squamous cell carcinoma proliferation and invasion by induction of an E-P cadherin switch via the WNT/β-catenin pathway

Guo

et al. 2020

Cell Oncol.

View full text Add to dashboard Cite

Purpose Persistent infection with high-risk human papillomavirus (HR-HPV) is thought to play a prominent role in the initiation and progression of almost all cases of cervical cancer. Previously, we and others found that microRNA 34a (miR-34a) may be regulated by HR-HPV E6 to contribute to the development of cervical cancer. Here, we aimed to identify the oncogenic potential and clinical significance of a known miR-34a target, WNT1, in cervical squamous cell carcinoma (SCC) development and to investigate the associated mechanisms underlying cervical SCC cell proliferation and invasion. Methods WNT1 and miR-34a expression levels were assessed in primary cervical lesions using immunohistochemistry and qRT-PCR, respectively. The cellular effects and the expression of its associated genes were examined in cervical SCC-derived Siha and Caski cells after siRNA-WNT1 (downregulation) or miR-34a mimic (upregulation) treatment. A cervical SCC xenograft mouse model was used to investigate the in vivo effects of miR-34a overexpression. HPV-16 E6/E7 expression was inhibited by gene promoter siRNA targeting, after which the levels of miR-34a and WNT1 were examined. Results WNT1 protein upregulation was found to be associated with a poor prognosis in cervical SCC patients. In vitro assays in Siha and Caski cells revealed that WNT1 downregulation decreased cell proliferation and invasion, inhibited WNT/β-catenin activation and affected the expression of E-cadherin and P-cadherin. MiR-34a upregulation resulted in decreased WNT1 expression. An inverse correlation between miR-34a and WNT1 expression was also observed in primary cervical SCC tissues. In addition, we found that MiR-34a could regulate an E-cadherin to P-cadherin switch (E-P cadherin switch) to inhibit cell proliferation and tumorigenesis in vitro and in vivo via inactivation of the WNT1/β-catenin pathway. Finally, we found that decreased HPV-16 E6/E7 expression resulted in miR-34a upregulation and WNT1 downregulation in Siha and Caski cells. Conclusions From our results we conclude that WNT1, as a target of miR-34a, can promote cervical SCC cell proliferation and invasion by induction of an E-P cadherin switch via the WNT1/β-catenin pathway. Our results may provide new options for the treatment of patients with cervical SCC.Keywords Cervical squamous cell carcinoma . miR-34a . WNT1 . E-cadherin . P-cadherin . Cadherin switch Electronic supplementary material The online version of this article (https://doi.

show abstract

“…HPVs persistent infection is the causative cause of cervical cancer . Some of the hrHPV persistent infection will be followed by viral DNA integration with human genome, resulting in over expression of two viral oncogene E6 and E7 .…”

Section: Discussionmentioning

confidence: 99%

“…HPVs persistent infection is the causative cause of cervical cancer. [32][33][34][35] Some of the hrHPV persistent infection will be followed by viral DNA integration with human genome, resulting in over expression of two viral oncogene E6 and E7. [36][37][38][39][40] These oncoproteins bind to the tumor suppressor genes p53 and the retinoblastoma protein (pRB), destroy their function, leading to dysplasia and invasive cancer.…”

Section: Discussionmentioning

confidence: 99%

REBACIN® as a noninvasive clinical intervention for high‐risk human papillomavirus persistent infection

Yang

Duan

et al. 2019

Intl Journal of Cancer

View full text Add to dashboard Cite

The development of highly sensitive HPV‐genotyping tests has opened the possibility of treating HPV‐infected women before high‐grade lesions appear. The lack of efficient intervention for persistent high‐risk HPV infection necessitates the need for development of novel therapeutic strategy. Here we demonstrate that REBACIN®, a proprietary antiviral biologics, has shown potent efficacy in the clearance of persistent HPV infections. Two independent parallel clinical studies were investigated, which a total of 199 patients were enrolled and randomly divided into a REBACIN®‐test group and a control group without treatment. The viral clearance rates for the REBACIN® groups were 61.5% (24/39) and 62.5% (35/56), respectively, for the two independent parallel studies. In contrast, the nontreatment groups showed self‐clearance rates at 20.0% (8/40) and 12.5% (8/64). We further found that REBACIN® was able to significantly repress the expression of HPV E6 and E7 oncogenes in TC‐1 and Hela cells. The two viral genes are well known for the development of high‐grade premalignancy lesion and cervical cancer. In a mouse model, REBACIN® was indicated to notably suppress E6/E7‐induced tumor growth, suggesting E6 and E7 oncogenes as a potential target of REBACIN®. Taken together, our studies shed light into the development of a novel noninvasive therapeutic intervention for clearance of persistent HPV infection with significant efficacy.

show abstract

HPV: Molecular pathways and targets

Cited by 136 publications

References 86 publications

MicroRNA Involvement in Signaling Pathways During Viral Infection

MicroRNA Involvement in Signaling Pathways During Viral Infection

WNT1, a target of miR-34a, promotes cervical squamous cell carcinoma proliferation and invasion by induction of an E-P cadherin switch via the WNT/β-catenin pathway

REBACIN® as a noninvasive clinical intervention for high‐risk human papillomavirus persistent infection

Contact Info

Product

Resources

About