Evidence map›Paper›PMID 27602489›Full record

ArticleOncotarget2016

Piwil2 is reactivated by HPV oncoproteins and initiates cell reprogramming via epigenetic regulation during cervical cancer tumorigenesis.

Dingqing Feng, Keqin Yan, Ying Zhou, Haiyan Liang, Jing Liang, Weidong Zhao, Zhongjun Dong, Bin Ling

Open access · diamondAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed, 1 pooled it
2.1field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

34 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 1 country.

Dingqing FengDepartment of Obstetrics and Gynecology, China-Japan Friendship Hospital, Beijing, China.
Keqin YanDepartment of Obstetrics and Gynecology, China-Japan Friendship Hospital, Beijing, China.
Ying ZhouDepartment of Obstetrics and Gynecology, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei, China.
Haiyan LiangDepartment of Obstetrics and Gynecology, China-Japan Friendship Hospital, Beijing, China.
Jing LiangDepartment of Obstetrics and Gynecology, China-Japan Friendship Hospital, Beijing, China.
Weidong ZhaoDepartment of Obstetrics and Gynecology, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei, China.
Zhongjun DongSchool of Medicine, Tsinghua University, Beijing, China.
Bin LingDepartment of Obstetrics and Gynecology, China-Japan Friendship Hospital, Beijing, China.
China-Japan Friendship Hospital · CNAnhui Medical University · CNTsinghua University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The human papillomavirus (HPV) oncoproteins E6 and E7 are risk factors that are primarily responsible for the initiation and progression of cervical cancer, and they play a key role in immortalization and transformation by reprogramming differentiating host epithelial cells. It is unclear how cervical epithelial cells transform into tumor-initiating cells (TICs). Here, we observed that the germ stem cell protein Piwil2 is expressed in pre-cancerous and malignant lesions of the cervix and cervical cancer cell lines with the exception of the non-HPV-infected C33a cell line. Knockdown of Piwil2 by shRNA led to a marked reduction in proliferation and colony formation, in vivo tumorigenicity, chemo-resistance, and the proportion of cancer stem-like cells. In contrast, Piwil2 overexpression induced malignant transformation of HaCaT cells and the acquisition of tumor-initiating capabilities. Gene-set enrichment analysis revealed embryonic stem cell (ESC) identity, malignant biological behavior, and specifically, activation targets of the cell reprogramming factors c-Myc, Klf4, Nanog, Oct4, and Sox2 in Piwil2-overexpressing HaCaT cells. We further confirmed that E6 and E7 reactivated Piwil2 and that E6 and E7 overexpression resulted in a similar gene-set enrichment pattern as Piwil2 overexpression in HaCaT cells. Moreover, Piwil2 overexpression or E6 and E7 activation induced H3K9 acetylation but reduced H3K9 trimethylation, which contributed to the epigenetic reprogramming and ESC signature maintenance, as predicted previously. Our study demonstrates that Piwil2, reactivated by the HPV oncoproteins E6 and E7, plays an essential role in the transformation of cervical epithelial cells to TICs via epigenetics-based cell reprogramming.

Indexed as

AnimalsArgonaute ProteinsCarcinogenesisCell Growth ProcessesCell Line, TumorCellular ReprogrammingEpigenetic RepressionFemaleGene Expression Regulation, NeoplasticHuman papillomavirus 16HumansKruppel-Like Factor 4MiceMice, NudeNeoplastic Stem CellsOncogene Proteins, ViralArgonaute ProteinsE6 protein, Human papillomavirus type 16KLF4 protein, humanKlf4 protein, mouseKruppel-Like Factor 4oncogene protein E7, Human papillomavirus type 16Oncogene Proteins, ViralPapillomavirus E7 ProteinsPIWIL2 protein, humanRepressor ProteinsRNA, Small Interferingcell reprogrammingcervical cancerHPV oncoproteinPiwil2tumor initiating cell

Identifiers

PMID27602489
PMCPMC5323100
OpenAlexW2507855701

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.