Evidence map›Paper›PMID 35312836›Full record

ArticleCancer chemotherapy and pharmacology2022

ATF4-mediated microRNA-145/HDAC4/p53 axis affects resistance of colorectal cancer cells to 5-fluorouracil by regulating autophagy.

Lin Zhao, Hong Chen, QingYi Zhang, Jin Ma, Hao Hu, Lu Xu

Abstract read
PubMed Publisher
In one paragraph

Article in Cancer chemotherapy and pharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.6field-weighted citation impact, top 18% 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

11 citing papers in PubMed, 20 citations in OpenAlex.

  1. Review
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  5. Article
  6. HDAC-driven mechanisms in anticancer resistance: epigenetics and beyond.Cancer drug resistance (Alhambra, Calif.) · 2024
    Review
  7. The Potential of Senescence as a Target for Developing Anticancer Therapy.International journal of molecular sciences · 2023
    Review
  8. Review
  9. Article
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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

6 authors at 1 institution in 1 country.

Lin Zhao *Department of Gastrointestinal Surgery, The First Affiliated Hospital of Soochow University, No. 899, Pinghai Road, Suzhou, 215006, Jiangsu, China.
Hong Chen *Department of General Surgery, Suzhou Dushu Lake Hospital Affiliated to Soochow University, Suzhou, 215000, China.
QingYi ZhangDepartment of Gastrointestinal Surgery, The First Affiliated Hospital of Soochow University, No. 899, Pinghai Road, Suzhou, 215006, Jiangsu, China.
Jin MaDepartment of Gastrointestinal Surgery, The First Affiliated Hospital of Soochow University, No. 899, Pinghai Road, Suzhou, 215006, Jiangsu, China.
Hao HuDepartment of Gastrointestinal Surgery, The First Affiliated Hospital of Soochow University, No. 899, Pinghai Road, Suzhou, 215006, Jiangsu, China. hhsuzhou@126.com.ORCID http://orcid.org/0000-0001-9271-2897
Lu XuDepartment of Gastrointestinal Surgery, The First Affiliated Hospital of Soochow University, No. 899, Pinghai Road, Suzhou, 215006, Jiangsu, China. luxu@suda.edu.cn.
Soochow University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe impact of activating transcription factor 4 (ATF4), differentially expressed in colorectal cancer (CRC), on 5-Fluorouracil (5-FU) chemoresistance has not been fully explained. The purpose of this study is to evaluate the clinical significance of ATF4-mediated microRNA-145 (miR-145)/histone deacetylase 4 (HDAC4)/p53 axis in CRC.

methodsInitially, the expression of ATF4, miR-145, HDAC4, and p53 in CRC tissues and cells was quantified by RT-qPCR and immunoblotting. Next, luciferase activity and chromatin immunoprecipitation assays were performed to verify the binding affinity among miR-145, ATF4, and HDAC4. Moreover, proliferation, clone formation, and apoptosis in CRC cells treated with 5-FU were assessed after gain- or loss-of-function of ATF4, miR-145, and/or HDAC4. Furthermore, the tumorigenicity and chemoresistance of CRC cells in mice were assayed for validating the in vitro findings.

resultsATF4 and HDAC4 were highly expressed, while miR-145 and p53 were poorly expressed in CRC tissues and cells. miR-145 targeted and negatively regulated HDAC4 to activate p53, and miR-145 expression was suppressed by ATF4. Of note, ATF4 facilitated cell proliferation and clone formation ability and repressed apoptosis to promote autophagy and chemoresistance of CRC cells by regulating the miR-145/HDAC4/p53 axis. In vivo experiment elucidated that ATF4-mediated miR-145/HDAC4/p53 axis enhanced tumorigenesis and resistance of CRC cells to 5-FU.

conclusionIn conclusion, ATF4-mediated miR-145 inhibition accelerated autophagy of CRC cells and boosted their resistance to 5-FU via the HDAC4/p53 axis.

Indexed as

Colorectal NeoplasmsMicroRNAsActivating Transcription Factor 4AnimalsAutophagyCell Line, TumorDrug Resistance, NeoplasmFluorouracilGene Expression Regulation, NeoplasticHistone DeacetylasesHumansMiceRepressor ProteinsTumor Suppressor Protein p53Activating Transcription Factor 4ATF4 protein, humanFluorouracilHDAC4 protein, humanHistone DeacetylasesMicroRNAsMIRN145a microRNA, mouseMIRN145 microRNA, humanRepressor ProteinsTumor Suppressor Protein p53ATF4AutophagyChemoresistanceColorectal cancerHDAC4microRNA-145p53

Identifiers

PMID35312836
OpenAlexW4220701523

What OpenQuestion holds

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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.