Evidence map›Paper›PMID 33971927›Full record

ArticleJournal of experimental & clinical cancer research : CR2021

Activation of the clock gene TIMELESS by H3k27 acetylation promotes colorectal cancer tumorigenesis by binding to Myosin-9.

Meng Cao, Yi Wang, Yijing Xiao, Dandan Zheng, Chunchun Zhi, Xin Xia, Xiaoqin Yuan

Open access · goldAbstract read
In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed, 1 pooled it
2.9field-weighted citation impact, top 9% 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

22 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.

  1. Pooled it
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  7. TIMELESS as a prognostic biomarker and therapeutic target in gastric cancer.Journal, genetic engineering & biotechnology · 2025
    Article
  8. Review
  9. Review
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  11. Non-Muscle Myosin II A: Friend or Foe in Cancer?International journal of molecular sciences · 2024
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  13. 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

7 authors at 3 institutions in 1 country.

Meng Cao *Department of General Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, China.
Yi Wang *Department of Anatomy, Histology and Embryology, Nanjing Medical University, Xuehai Building, Rm D509, 101 Longmian Avenue, Jiangning District, Nanjing, 211166, China.
Yijing Xiao *Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, 210029, China.
Dandan ZhengDepartment of Anatomy, Histology and Embryology, Nanjing Medical University, Xuehai Building, Rm D509, 101 Longmian Avenue, Jiangning District, Nanjing, 211166, China.
Chunchun ZhiDepartment of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, 210002, China.
Xin XiaDepartment of Anatomy, Histology and Embryology, Nanjing Medical University, Xuehai Building, Rm D509, 101 Longmian Avenue, Jiangning District, Nanjing, 211166, China.
Xiaoqin YuanDepartment of Anatomy, Histology and Embryology, Nanjing Medical University, Xuehai Building, Rm D509, 101 Longmian Avenue, Jiangning District, Nanjing, 211166, China. yuanxq@njmu.edu.cn.
Nanjing Medical University · CNNanjing Drum Tower Hospital · CNNanjing University · CN

Funding

National Natural Science Foundation of China 81972288Natural Science Foundation of Jiangsu Province BK20191353
6 · The paper itself

Abstract

backgroundColorectal cancer (CRC) is a common tumor characterized by its high mortality. However, the underlying molecular mechanisms that drive CRC tumorigenesis are unclear. Clock genes have important roles in tumor development. In the present study, the expression and functions of clock gene TIMELESS (encoding the Timeless protein) in CRC were investigated.

methodsImmunohistochemistry, cell proliferation, migration, invasion, EMT and xenograft tumor experiments were used to prove the function of Timeless in the tumorigenesis of CRC. Immunoprecipitation, mass spectrometry, Immunofluorescence and Chromatin immunoprecipitation (ChIP) were utilized to clarify the mechanism of Timeless in regulating CRC tumorigenesis.

resultsWe found that Timeless was upregulated in CRC tissues compared with corresponding normal tissues and its expression was closely associated with the TNM stages and overall survival of CRC patients. Functional studies demonstrated that Timeless promoted the proliferation, invasion, and EMT of CRC cells in vitro and in vivo. Mechanistic investigations showed that Timeless activated the β-catenin signal pathway by binding to Myosin-9, which binds to β-catenin to induce its nuclear translocation. The upregulation of Timeless was attributed to CREB-binding protein (CBP)/p300-mediated H3K27 acetylation of the promoter region of Timeless.

conclusionTimeless regulates the tumorigenesis of CRC by binding to and regulating myosin-9, suggesting Timeless might be a potential prognostic biomarker and therapeutic target for CRC.

Indexed as

Wnt Signaling PathwayAcetylationAnimalsCaco-2 CellsCarcinogenesisCell Cycle ProteinsCell Line, TumorCell ProliferationColorectal NeoplasmsFemaleHCT116 CellsHeterograftsHistonesHT29 CellsHumansIntracellular Signaling Peptides and ProteinsCell Cycle ProteinsHistonesIntracellular Signaling Peptides and ProteinsMYH9 protein, humanMyosin Heavy ChainsTIMELESS protein, humanColorectal cancerMyosin-9TimelessWnt/β-catenin pathway

Identifiers

PMID33971927
PMCPMC8108341
OpenAlexW3163192164

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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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.