Evidence map›Paper›PMID 29472532›Full record

ArticleCell death & disease2018

Co-inhibition of BET proteins and NF-κB as a potential therapy for colorectal cancer through synergistic inhibiting MYC and FOXM1 expressions.

Tingyu Wu, Guanghui Wang, Wei Chen, Zhehui Zhu, Yun Liu, Zhenyu Huang, Yuji Huang, Peng Du, Yili Yang, Chen-Ying Liu and 1 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
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 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
1.5field-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

27 citing papers in PubMed, 38 citations in OpenAlex.

  1. Article
  2. PARP1 Suppression Drives ROS Resistance in Aneuploid Cancer Cells.bioRxiv : the preprint server for biology · 2026
    Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Review
  9. Review
  10. Review
  11. Review
  12. Significant position of C-myc in colorectal cancer: a promising therapeutic target.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2022
    Review
  13. Review
  14. Review
  15. Review
  16. Review
  17. BET Proteins as Attractive Targets for Cancer Therapeutics.International journal of molecular sciences · 2021
    Review
  18. Article
  19. Article
  20. Review
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

11 authors at 4 institutions in 2 countries.

Tingyu WuDepartment of Colorectal Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Guanghui WangDepartment of Colorectal Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Wei ChenDepartment of Colorectal Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Zhehui ZhuDepartment of Colorectal Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yun LiuDepartment of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Zhenyu HuangDepartment of Colorectal Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yuji HuangDepartment of Colorectal Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Peng DuDepartment of Colorectal Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yili YangSuzhou Institute of Systems Medicine, Center for Systems Medicine, Chinese Academy of Medical Sciences, Suzhou, China.
Chen-Ying LiuDepartment of Colorectal Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. liuchenying@xinhuamed.com.cn.
Long CuiDepartment of Colorectal Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. cuilong@xinhuamed.com.cn.ORCID 0000-0003-1838-4471
Shanghai Jiao Tong University · CNChinese Academy of Medical Sciences & Peking Union Medical College · CNThe University of Texas MD Anderson Cancer Center · USXinHua Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The bromodomain and extra-terminal domain inhibitors (BETi) are promising epigenetic drugs for the treatment of various cancers through suppression of oncogenic transcription factors. However, only a subset of colorectal cancer (CRC) cells response to BETi. We investigate additional agents that could be combined with BETi to overcome this obstacle. JQ1-resistant CRC cells were used for screening of the effective combination therapies with JQ1. RNA-seq was performed to explore the mechanism of synergistic effect. The efficacy of combinational treatment was tested in the CRC cell line- and patient-derived xenograft (PDX) models. In BETi-sensitive CRC cells, JQ1 also impaired tumor angiogenesis through the c-myc/miR-17-92/CTGF+THBS1 axis. CTGF knockdown moderately counteracted anti-angiogenic effect of JQ1 and led to partially attenuated tumor regression. JQ1 decreased c-myc expression and NF-κB activity in BETi-sensitive CRC cells but not in resistant cells. Bortezomib synergistically sensitized BETi-resistant cells to the JQ1 treatment, and JQ1+Bortezomib induced G2/M arrest in CRC cells. Mechanistically, inhibition of NF-κB by Bortezomib or NF-κB inhibitor or IKK1/2 siRNA all rendered BETi-resistant cells more sensitive to BETi by synergistic repression of c-myc, which in turn induces GADD45s' expression, and by synergistic repression of FOXM1 which in turn inhibit G2/M checkpoint genes' expression. Activation of NF-κB by IκBα siRNA induced resistance to JQ1 in BETi-sensitive CRC cells. Last, JQ1+Bortezomib inhibited tumor growth and angiogenesis in CRC cell line xenograft model and four PDX models. Our results indicate that anti-angiogenic effect of JQ1 plays a vital role in therapeutic effect of JQ1 in CRC, and provide a rationale for combined inhibition of BET proteins and NF-κB as a potential therapy for CRC.

Indexed as

AnimalsAntineoplastic AgentsAzepinesBortezomibCell Cycle CheckpointsCell Line, TumorColorectal NeoplasmsDrug SynergismFemaleForkhead Box Protein M1Gene Expression Regulation, NeoplasticHumansMiceMice, NudeNF-kappa BNuclear ProteinsAntineoplastic AgentsAzepinesBortezomibForkhead Box Protein M1Foxm1 protein, mouse(+)-JQ1 compoundNF-kappa BNuclear ProteinsOncogene Protein p55(v-myc)Proto-Oncogene Proteins c-mycTriazoles

Identifiers

PMID29472532
PMCPMC5833769
OpenAlexW2791595469

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.