Evidence map›Paper›PMID 25924900›Full record

ArticleBMC cancer2015

DNA Polymerases as targets for gene therapy of hepatocellular carcinoma.

Hao Liu, Qun Wei, Jia Wang, Xiaoming Huang, Chunchun Li, Qiaoli Zheng, Jiang Cao, Zhenyu Jia

Open access · goldAbstract read
In one paragraph

Article in BMC cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.0field-weighted citation impact, top 20% 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

6 citing papers in PubMed, 17 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 6 institutions in 1 country.

Hao LiuInstitute of Occupational Diseases, Zhejiang Academy of Medical Sciences, 182 Tianmushan Road, Hangzhou, 310013, Zhejiang, P.R. China. liuh_1985@163.com.
Qun WeiDepartment of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou, 310016, Zhejiang, P.R. China. ellequn@126.com.
Jia WangInstitute of Occupational Diseases, Zhejiang Academy of Medical Sciences, 182 Tianmushan Road, Hangzhou, 310013, Zhejiang, P.R. China. 845834078@qq.com.
Xiaoming HuangInstitute of Occupational Diseases, Zhejiang Academy of Medical Sciences, 182 Tianmushan Road, Hangzhou, 310013, Zhejiang, P.R. China. hxm349@yahoo.com.cn.
Chunchun LiClinical Research Center, The Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, 310009, Zhejiang, P.R. China. lichunchun.1@163.com.
Qiaoli ZhengClinical Research Center, The Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, 310009, Zhejiang, P.R. China. qlzheng@hotmail.com.
Jiang CaoClinical Research Center, The Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, 310009, Zhejiang, P.R. China. caoj@zju.edu.cn.
Zhenyu JiaInstitute of Occupational Diseases, Zhejiang Academy of Medical Sciences, 182 Tianmushan Road, Hangzhou, 310013, Zhejiang, P.R. China. zhenyujia@yahoo.com.
Second Affiliated Hospital of Zhejiang University · CNZhejiang Academy of Medical Sciences · CNChinese Academy of Medical Sciences & Peking Union Medical College · CNSir Run Run Shaw Hospital · CNWenzhou Medical University · CNZhejiang University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundHepatocyte carcinoma (HCC) is one of the most common malignancies worldwide. Despite many achievements in diagnosis and treatment, HCC mortality remains high due to the malignant nature of the disease. Novel approaches, especially for targeted therapy, are being extensively explored. Gene therapy is ideal for such purpose for its specific expression of exogenous genes in HCC cells driven by tissue-specific promoter. However strategies based on correction of mutations or altered expressions of genes responsible for the development/progression of HCC have limitations because these aberrant molecules are not presented in all cancerous cells. In the current work, we adopted a novel strategy by targeting the DNA replication step which is essential for proliferation of every cancer cell.

methodsA recombinant adenovirus with alpha fetoprotein (AFP) promoter-controlled expressions of artificial microRNAs targeting DNA polymerases α, δ, ε and recombinant active Caspase 3, namely Ad/AFP-Casp-AFP-amiR, was constructed.

resultsThe artificial microRNAs could efficiently inhibit the expression of the target polymerases in AFP-positive HCC cells at both RNA and protein levels, and HCC cells treated with the recombinant virus Ad/AFP-Casp-AFP-amiR exhibited significant G0/1 phase arrest. The proliferation of HCC cells were significantly inhibited by Ad/AFP-Casp-AFP-amiR with increased apoptosis. On the contrary, the recombinant adenovirus Ad/AFP-Casp-AFP-amiR did not inhibit the expression of DNA polymerases α, δ or ε in AFP-negative human normal liver cell HL7702, and showed no effect on the cell cycle progression, proliferation or apoptosis.

conclusionsInhibition of DNA polymerases α, δ and ε by AFP promoter-driven artificial microRNAs may lead to effective growth arrest of AFP-positive HCC cells, which may represent a novel strategy for gene therapy by targeting the genes that are essential for the growth/proliferation of cancer cells, avoiding the limitations set by any of the individually altered gene.

Indexed as

AdenoviridaeAnimalsApoptosisCarcinoma, HepatocellularCell Line, TumorDNA Polymerase IDNA Polymerase IIDNA Polymerase IIIGenetic TherapyHumansLiver NeoplasmsMiceMicroRNAsMolecular Targeted TherapyPromoter Regions, GeneticXenograft Model Antitumor AssaysDNA Polymerase IDNA Polymerase IIDNA Polymerase IIIMicroRNAs

Identifiers

PMID25924900
PMCPMC4423151
OpenAlexW2053762560

What OpenQuestion holds

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LicenceCC BY
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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.