Evidence map›Paper›PMID 24708873›Full record

ArticleMolecular cancer2014

miR-375 activates p21 and suppresses telomerase activity by coordinately regulating HPV E6/E7, E6AP, CIP2A, and 14-3-3ζ.

Hyun Min Jung, Brittany L Phillips, Edward Kl Chan

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

Article in Molecular cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed, 1 pooled it
4.9field-weighted citation impact, top 4% 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

50 citing papers in PubMed, 1 synthesis or guideline pooled it, 97 citations in OpenAlex.

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  15. New insights of epigenetics in vascular and cellular senescence.Journal of translational internal medicine · 2021
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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

3 authors at 1 institution in 1 country.

Hyun Min Jung
Brittany L Phillips
Edward Kl ChanDepartment of Oral Biology, University of Florida, 1395 Center Drive, Gainesville, FL 32610, USA. echan@ufl.edu.
University of Florida · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundWhile microRNAs (miRNAs) are extensively studied in post-transcriptional regulation of gene expressions in many biological processes, cellular miRNA-mediated regulation of viral genes remains unclear. In particular, the interplay between human papillomavirus (HPV) genes and miRNAs and how these interactions contribute to HPV-associated cancers remain elusive.

methodsTransient transfection of miR-375-mimic was used to compensate the loss-of-function of miR-375 in HPV-positive cancer. Regulation of oncogenic molecules and their downstream molecules via miR-375 in HPV-positive cancer was investigated using qRT-PCR, western blot, dual luciferase assay, indirect immunofluorescence analysis. All experiments were conducted at least three times to achieve statistical significance determined by Student t-test.

resultsIn this study, we demonstrated how miR-375 negatively regulates HPV16 and 18 transcripts. We also found a cellular protein, E6-associated protein (E6AP), directly regulated by miR-375. miR-375-mediated repression of HPV transcripts and E6AP elevated major tumor suppressors p53, p21, and retinoblastoma protein 1 (RB). Cooperative regulation of miR-375 targets along with the increase of tumor suppressors led to ~60% reduction of telomerase reverse transcriptase (TERT) transcription followed by ~35% decrease of telomerase activity. Furthermore, miR-375-mediated regulation of 14-3-3ζ contributes to decrease telomerase activity by altering nuclear translocation of TERT.

conclusionTaken together, miR-375-mediated suppression of multiple oncogenic components in HPV-associated carcinogenesis generates a cumulative biological response to rescue key tumor suppressors and diminish telomerase activity, which results in cell cycle arrest and cell proliferation inhibition.

Indexed as

14-3-3 ProteinsAutoantigensCell Line, TumorDNA-Binding ProteinsFemaleGene Expression Regulation, NeoplasticGene Expression Regulation, ViralHumansIntracellular Signaling Peptides and ProteinsMembrane ProteinsMicroRNAsOncogene Proteins, ViralPapillomavirus E7 ProteinsRepressor ProteinsRetinoblastoma Proteinrho GTP-Binding Proteins14-3-3 ProteinsAutoantigensCIP2A protein, humanDNA-Binding ProteinsE6 protein, Human papillomavirus type 16E6 protein, Human papillomavirus type 18Intracellular Signaling Peptides and ProteinsMembrane ProteinsMicroRNAsMIRN375 microRNA, humanoncogene protein E7, Human papillomavirus type 16Oncogene Proteins, ViralPapillomavirus E7 ProteinsRepressor ProteinsRetinoblastoma Proteinrho GTP-Binding ProteinsUBE3A protein, humanUbiquitin-Protein Ligases

Identifiers

PMID24708873
PMCPMC4021670
OpenAlexW2139975735

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.