scholarly journals Interferon-β Induced microRNA-129-5p Down-Regulates HPV-18 E6 and E7 Viral Gene Expression by Targeting SP1 in Cervical Cancer Cells

PLoS ONE ◽  
2013 ◽  
Vol 8 (12) ◽  
pp. e81366 ◽  
Author(s):  
Jiarong Zhang ◽  
Shuangdi Li ◽  
Qin Yan ◽  
Xiaoyue Chen ◽  
Yixia Yang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cervical Cancer ◽  
Cancer Cells ◽  
Viral Gene Expression ◽  
Viral Gene ◽  
Interferon Β ◽  
Cervical Cancer Cells ◽  
E6 And E7 ◽  
Hpv 18

scholarly journals Human Papillomavirus E6/E7 and Long Noncoding RNA TMPOP2 Mutually Upregulated Gene Expression in Cervical Cancer Cells

2019 ◽  
Vol 93 (8) ◽  
Author(s):  
Hongpeng He ◽  
Xiang Liu ◽  
Yue Liu ◽  
Mengmeng Zhang ◽  
Yongwei Lai ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Cancer Cells ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Human Papillomaviruses ◽  
Cervical Cancer Cells ◽  
E6 And E7

ABSTRACT TMPOP2 was previously suggested to be an oncogenic long noncoding RNA which is excessively expressed in cervical cancer cells and inhibits E-cadherin gene expression by recruiting transcription repressor EZH2 to the gene promoter. So far, the function and regulation of TMPOP2 in cervical cancer remain largely unknown. Herein, we found that TMPOP2 expression was correlated with human papillomavirus 16/18 (HPV16/18) E6 and E7 in cervical cancer cell lines CaSki and HeLa. Tumor suppressor p53, which is targeted for degradation by HPV16/18, was demonstrated to associate with two p53 response elements in the TMPOP2 promoter to repress the transcription of the TMPOP2 gene. Reciprocally, ectopic expression of TMPOP2 was demonstrated to sequester tumor repressor microRNAs (miRNAs) miR-375 and miR-139 which target HPV16/18 E6/E7 mRNA and resulted in an upregulation of HPV16/18 E6/E7 genes. Thereby, HPV16/18 E6/E7 and the long noncoding RNA (lncRNA) TMPOP2 form a positive feedback loop to mutually derepress gene expression in cervical cancer cells. Moreover, results of RNA sequencing and cell cycle analysis showed that knockdown of TMPOP2 impaired the expression of cell cycle genes, induced cell cycle arrest, and inhibited HeLa cell proliferation. Together, our results indicate that TMPOP2 and HPV16/18 E6/E7 mutually strengthen their expression in cervical cancer cells to enhance tumorigenic activities. IMPORTANCE Human papillomaviruses 16 and 18 (HPV16/18) are the main causative agents of cervical cancer. Viral proteins HPV16/18 E6 and E7 are constitutively expressed in cancer cells to maintain oncogenic phenotypes. Accumulating evidences suggest that HPVs are correlated with the deregulation of long noncoding RNAs (lncRNAs) in cervical cancer, although the mechanism was unexplored in most cases. TMPOP2 is a newly identified lncRNA excessively expressed in cervical cancer. However, the mechanism for the upregulation of TMPOP2 in cervical cancer cells remains largely unknown and its relationship with HPVs is still elusive. The significance of our research is in revealing the mutual upregulation of HPV16/18 E6/E7 and TMPOP2 with the molecular mechanisms explored. This study will expand our understandings of the oncogenic activities of human papillomaviruses and lncRNAs.

scholarly journals Characterization of HPV integration, viral gene expression and E6E7 alternative transcripts by RNA-Seq: A descriptive study in invasive cervical cancer

Genomics ◽  
2019 ◽  
Vol 111 (6) ◽  
pp. 1853-1861 ◽  
Author(s):  
Ayslan C. Brant ◽  
Albert N. Menezes ◽  
Shayany P. Felix ◽  
Liz M. de Almeida ◽  
Michael Sammeth ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cervical Cancer ◽  
Invasive Cervical Cancer ◽  
Viral Gene Expression ◽  
Descriptive Study ◽  
Viral Gene ◽  
Rna Seq ◽  
Alternative Transcripts

Silencing of HPV 18 Oncoproteins With RNA Interference Causes Growth Inhibition of Cervical Cancer Cells

2007 ◽  
Vol 14 (1) ◽  
pp. 20-28 ◽  
Author(s):  
Jayanthi S. Lea ◽  
Noriaki Sunaga ◽  
Mitsuo Sato ◽  
Geetha Kalahasti ◽  
David S. Miller ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Rna Interference ◽  
Growth Inhibition ◽  
Cancer Cells ◽  
Cervical Cancer Cells ◽  
Hpv 18

scholarly journals Transcriptomic analyses of gene expression by CRISPR knockout of miR-214 in cervical cancer cells

Genomics ◽  
2020 ◽  
Vol 112 (2) ◽  
pp. 1490-1499 ◽  
Author(s):  
Prakriti Sen ◽  
Sayam Ghosal ◽  
Rudranil Hazra ◽  
Solomon Arega ◽  
Rimjhim Mohanty ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cervical Cancer ◽  
Cancer Cells ◽  
Cervical Cancer Cells

scholarly journals Endogenous Human Papillomavirus E6 and E7 Proteins Differentially Regulate Proliferation, Senescence, and Apoptosis in HeLa Cervical Carcinoma Cells

2003 ◽  
Vol 77 (2) ◽  
pp. 1551-1563 ◽  
Author(s):  
Rosa Anna DeFilippis ◽  
Edward C. Goodwin ◽  
Lingling Wu ◽  
Daniel DiMaio
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Cancer Cells ◽  
Cervical Carcinoma ◽  
Carcinoma Cells ◽  
Rb Pathway ◽  
Cervical Cancer Cells ◽  
E6 And E7 ◽  
E7 Proteins ◽  
E6 Protein

ABSTRACT Cervical cancer cells express high-risk human papillomavirus (HPV) E6 and E7 proteins, and repression of HPV gene expression causes the cells to cease proliferation and undergo senescence. However, it is not known whether both HPV proteins are required to maintain the proliferative state of cervical cancer cells, or whether mutations that accumulate during carcinogenesis eliminate the need for one or the other of them. To address these questions, we used the bovine papillomavirus E2 protein to repress the expression of either the E6 protein or the E7 protein encoded by integrated HPV18 DNA in HeLa cervical carcinoma cells. Repression of the E7 protein activated the Rb pathway but not the p53 pathway and triggered senescence, whereas repression of the E6 protein activated the p53 pathway but not the Rb pathway and triggered both senescence and apoptosis. Telomerase activity, cyclin-dependent kinase activity, and expression of c-myc were markedly inhibited by repression of either E6 or E7. These results demonstrate that continuous expression of both the E6 and the E7 protein is required for optimal proliferation of cervical carcinoma cells and that the two viral proteins exert distinct effects on cell survival and proliferation. Therefore, strategies that inhibit the expression or activity of either viral protein are likely to inhibit the growth of HPV-associated cancers.

Wogonin induces apoptosis by suppressing E6 and E7 expressions and activating intrinsic signaling pathways in HPV-16 cervical cancer cells

2013 ◽  
Vol 29 (4) ◽  
pp. 259-272 ◽  
Author(s):  
Man Sub Kim ◽  
Yesol Bak ◽  
Yun Sun Park ◽  
Dong Hun Lee ◽  
Jung Hee Kim ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Signaling Pathways ◽  
Hpv 16 ◽  
Cervical Cancer Cells ◽  
E6 And E7

scholarly journals Utilization of a cell-penetrating peptide-adaptor for delivery of HPV protein E2 into cervical cancer cells to arrest cell growth and promote cell death

2020 ◽  
Author(s):  
Julia C. LeCher ◽  
Hope L. Didier ◽  
Robert L. Dickson ◽  
Lauren R. Slaughter ◽  
Juana C. Bejarano ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Cell Penetrating Peptides ◽  
Viral Integration ◽  
E2 Protein ◽  
Cell Penetrating ◽  
Cervical Cancer Cells ◽  
E6 And E7

AbstractCervical cancer is the second leading cause of cancer deaths in women worldwide. Human papillomavirus (HPV) is the causative agent of nearly all forms of cervical cancer, which arises upon viral integration into the host genome and concurrent loss of regulatory gene E2. E2 protein regulates viral oncoproteins E6 and E7. Loss of E2 upon viral integration results in unregulated expression and activity of E6 and E7, which promotes carcinogenesis. Previous studies using gene-based delivery show that reintroduction of E2 into cervical cancer cell lines can reduce proliferative capacity and promote apoptosis. However, owing in part to limitations on transfection in vivo, E2 reintroduction has yet to achieve therapeutic usefulness. A promising new approach is protein-based delivery systems utilizing cell-penetrating peptides (CPPs). CPPs readily traverse the plasma membrane and are able to carry with them biomolecular ‘cargos’ to which they are attached. Though more than two decades of research have been dedicated to their development for delivery of biomolecular therapeutics, the full potential of CPPs has yet to be realized as the field is hindered by the tendency of CPP-linked cargos to be trapped in endosomes as well as having significant off-target potential in vivo. Using a CPP-adaptor system that reversibly binds cargo thereby overcoming the endosomal entrapment that hampers other CPP methods, bioactive E2 protein was delivered into living cervical cancer cells, resulting in inhibition of cellular proliferation and promotion of cell death in a time- and dose-dependent manner. The results suggest that this nucleic acid- and virus-free delivery method could be harnessed to develop novel, effective protein therapeutics for treatment of cervical cancer.

scholarly journals Human papillomavirus type 18 oncoproteins exert their oncogenicity in esophageal and tongue squamous cell carcinoma cell lines distinctly

2019 ◽  
Author(s):  
Siaw Shi Boon ◽  
Zigui Chen ◽  
Karen Lee Yin Ching ◽  
Liuyang Cai ◽  
Jintao Li ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Tongue Cancer ◽  
Cancer Cell Lines ◽  
Cervical Cancer Cells ◽  
Esophageal Cancer Cell ◽  
Hpv18 E6 ◽  
E6 And E7

Abstract Background: Increasing evidence indicates an etiological role of human papillomavirus (HPV) in head and neck cancers, particularly oropharyngeal squamous cell carcinoma (OPSCC). However, the association between HPV and other cancers, including esophageal and tongue remains unclear. Methods: We compared the molecular characteristics of HPV18 E6 and E7 in esophageal (EC109 and EC9706) and tongue (Tca83) cancer cell lines with reference to cervical cancer (HeLa). We studied the expression of HPV transcripts using Next Generation RNA sequencing. We used small interference RNA (siRNA) against HPV18 oncoproteins to verify their oncogenic roles in molecular signaling, targeting metalloproteases and apoptotic pathways in these cancers. Results: We observed that the HPV transcription profiles of esophageal and tongue cancer cells mimicked that of cervical cancer cells, with notable disruption of E2, and expression of E6, spliced E6 (E6 * ), E7, E1 and L1 transcripts. As with cervical cancer cells, p53 and its downstream transactivation target, p21, were found to be the major targets of E6 in esophageal and tongue cancer cell lines. Intriguingly, E7 preferentially targeted p130 in the two esophageal cancer cell lines, instead of pRb as in cervical cancer. Tca83 exhibited an E7 to E6 transcript ratio comparable to HeLa (cervix), targeted the ERK1/2 and MMP2 pathways, and was dependent on E6 and E7 to survive and proliferate. In contrast, both the esophageal cancer cell lines were distinct from HeLa in these aspects. Conclusion: This is the first study to delineate the transcripts expression and role of HPV18 E6 and E7 in esophageal and tongue cancer cell lines. This findings suggest that HPV18 plays an oncogenic role in inducing these cancers, albeit via distinct pathways than those observed in cervical cancer.

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