Evidence map›Paper›PMID 29706629›Full record

ArticleCell death & disease2018

Targeting the miR-665-3p-ATG4B-autophagy axis relieves inflammation and apoptosis in intestinal ischemia/reperfusion.

Zhenlu Li, Guangzhi Wang, Dongcheng Feng, Guo Zu, Yang Li, Xue Shi, Yan Zhao, Huirong Jing, Shili Ning, Weidong Le and 2 more

Open access · goldAbstract read
In one paragraph

Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed
9.1field-weighted citation impact, top 1% 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

46 citing papers in PubMed, 88 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

12 authors at 1 institution in 1 country.

Zhenlu LiDepartment of General Surgery, The Second Hospital of Dalian Medical University, 116023, Dalian, China.
Guangzhi WangDepartment of General Surgery, The Second Hospital of Dalian Medical University, 116023, Dalian, China.
Dongcheng FengDepartment of General Surgery, The Second Hospital of Dalian Medical University, 116023, Dalian, China.
Guo ZuDepartment of General Surgery, The Second Hospital of Dalian Medical University, 116023, Dalian, China.
Yang LiDepartment of General Surgery, The Second Hospital of Dalian Medical University, 116023, Dalian, China.
Xue ShiDepartment of Pharmacology, Dalian Medical University, 116044, Dalian, China.
Yan ZhaoDepartment of Pharmacology, Dalian Medical University, 116044, Dalian, China.
Huirong JingDepartment of General Surgery, The Second Hospital of Dalian Medical University, 116023, Dalian, China.
Shili NingDepartment of General Surgery, The Second Hospital of Dalian Medical University, 116023, Dalian, China.
Weidong LeClinical Research Center on Neurological Diseases, the First Affiliated Hospital of Dalian Medical University, 116011, Dalian, China.
Jihong YaoDepartment of Pharmacology, Dalian Medical University, 116044, Dalian, China. yaojihong65@hotmail.com.
Xiaofeng TianDepartment of General Surgery, The Second Hospital of Dalian Medical University, 116023, Dalian, China. txfdl@dmu.edu.cn.ORCID 0000-0002-6654-2270
Dalian Medical University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Autophagy is an essential cytoprotective response against pathologic stresses that selectively degrades damaged cellular components. Impaired autophagy contributes to organ injury in multiple diseases, including ischemia/reperfusion (I/R), but the exact mechanism by which impaired autophagy is regulated remains unclear. Several researchers have demonstrated that microRNAs (miRNAs) negatively regulate autophagy by targeting autophagy-related genes (ATGs). Therefore, the effect of ATG-related miRNAs on I/R remains a promising research avenue. In our study, we found that autophagy flux is impaired during intestinal I/R. A miRNA microarray analysis showed that miR-665-3p was highly expressed in the I/R group, which was confirmed by qRT-PCR. Then, we predicted and proved that miR-665-3p negatively regulates ATG4B expression in Caco-2 and IEC-6 cells. In ileum biopsy samples from patients with intestinal infarction, there was an inverse correlation between miR-665-3p and ATG4B expression, which supports the in vitro findings. Moreover, based on miR-665-3p regulation of autophagy in response to hypoxia/reoxygenation in vitro, gain-of-function and loss-of-function approaches were used to investigate the therapeutic potential of miR-665-3p. Additionally, we provide evidence that ATG4B is indispensable for protection upon inhibition of miR-665-3p. Finally, we observed that locked nucleic acid-modified inhibition of miR-665-3p in vivo alleviates I/R-induced systemic inflammation and apoptosis via recovery of autophagic flux. Our study highlights miR-665-3p as a novel small molecule that regulates autophagy by targeting ATG4B, suggesting that miR-665-3p inhibition may be a potential therapeutic approach against inflammation and apoptosis for the clinical treatment of intestinal I/R.

Indexed as

ApoptosisAutophagyAnimalsAutophagy-Related ProteinsCaco-2 CellsCysteine EndopeptidasesDisease Models, AnimalEnterocytesGene Expression RegulationHumansIleumInflammationMaleMice, Inbred C57BLMicroRNAsReperfusion InjuryATG4B protein, humanAtg4b protein, mouseAutophagy-Related ProteinsCysteine EndopeptidasesMicroRNAsMIRN665 microRNA, human

Identifiers

PMID29706629
PMCPMC5924757
OpenAlexW2800443090

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.