Evidence map›Paper›PMID 22912826›Full record

ArticlePloS one2012

The effect of miR-338-3p on HBx deletion-mutant (HBx-d382) mediated liver-cell proliferation through CyclinD1 regulation.

Xiaoyu Fu, Deming Tan, Zhouhua Hou, Zhiliang Hu, Guozhen Liu, Yi Ouyang, Fei Liu

RetractedOpen access · goldAbstract readRetracted Publication
In one paragraph

Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.8field-weighted citation impact, top 15% 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

21 citing papers in PubMed, 34 citations in OpenAlex.

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  16. Regulation of viral oncogenesis by microRNAs.Molecular & cellular oncology · 2014
    Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 1 country.

Xiaoyu FuDepartment of Infectious Disease, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Deming Tan
Zhouhua Hou
Zhiliang Hu
Guozhen Liu
Yi Ouyang
Fei Liu
Xiangya Hospital Central South University · CNCentral South University · CNNanjing Second Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveHepatitis B Virus (HBV) DNA integration and HBV X (HBx) deletion mutation occurs in HBV-positive liver cancer patients, and C-terminal deletion in HBx gene mutants are highly associated with hepatocarcinogenesis. Our previous study found that the HBx-d382 deletion mutant (deleted at nt 382-400) can down-regulate miR-338-3p expression in HBx-expressing cells. The aim of the present study is to examine the role of miR-338-3p in the HBx-d382-mediated liver-cell proliferation.

methodsWe established HBx-expressing LO2 cells by Lipofectamine 2000 transfection. A miR-338-3p mimics or inhibitor was transfected into LO2/HBx-d382 and LO2/HBx cells using miR-NC as a control miRNA. In silico analysis of potential miR-338-3p targets revealed that miR-338-3p could target the cell cycle regulatory protein CyclinD1. To confirm that CyclinD1 is negatively regulated by miR-338-3p, we constructed luciferase reporters with wild-type and mutated CyclinD1-3'UTR target sites for miR-338-3p binding. We examined the CyclinD1 expression by real-time PCR and western blot, and proliferation activity by flow cytometric cell cycle analysis, Edu incorporation, and soft agar colony.

resultsHBx-d382 exhibited enhanced proliferation and CyclinD1 expression in LO2 cells. miR-338-3p expression inhibited cell proliferation in LO2/HBx-d382 cells (and LO2/HBx cells), and also negatively regulated CyclinD1 protein expression. Of the two putative miR-338-3p binding sites in the CyclinD1-3'UTR region, the effect of miR-338-3p on the second binding site (nt 2397-2403) was required for the inhibition.

conclusionmiR-338-3p can directly regulate CyclinD1 expression through binding to the CyclinD1-3'UTR region, mainly at nt 2397-2403. Down-regulation of miR-338-3p expression is required for liver cell proliferation in both LO2/HBx and LO2/HBx-d382 mutant cells, although the effect is more pronounced in LO2/HBx-d382 cells. Our study elucidated a novel mechanism, from a new miRNA-regulation perspective, underlying the propensity of HBx deletion mutants to induce hepatocarcinogenesis at a faster rate than HBx.

Indexed as

Blotting, WesternCell ProliferationColony-Forming Units AssayCyclin D1DNA PrimersFlow CytometryHepatitis B virusHumansLipidsLiver NeoplasmsLuciferasesMicroRNAsReal-Time Polymerase Chain ReactionReverse Transcriptase Polymerase Chain ReactionSequence DeletionTrans-ActivatorsCCND1 protein, humanCyclin D1DNA Primershepatitis B virus X proteinLipidsLipofectamineLuciferasesMicroRNAsMIRN338 microRNA, humanTrans-ActivatorsViral Regulatory and Accessory Proteins

Identifiers

PMID22912826
PMCPMC3422285
OpenAlexW1997355605

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.