Evidence map›Paper›PMID 38341472›Full record

ArticleOncogene2024

TMEM65 promotes gastric tumorigenesis by targeting YWHAZ to activate PI3K-Akt-mTOR pathway and is a therapeutic target.

Lingxue Shi, Xiaohong Wang, Shang Guo, Hongyan Gou, Haiyun Shang, Xiaojia Jiang, Chunxian Wei, Jia Wang, Chao Li, Lihong Wang and 3 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Oncogene, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
3.5field-weighted citation impact, top 7% 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

13 citing papers in PubMed, 15 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Functional Role of COP1 Gene in Hepatocellular Carcinoma Lipid Metabolism and Stemness.Genes to cells : devoted to molecular & cellular mechanisms · 2026
    Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Implication of protein post translational modifications in gastric cancer.Frontiers in cell and developmental biology · 2025
    Review
  13. 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

13 authors at 2 institutions in 2 countries.

Lingxue Shi *Departments of Endoscopy Center, The First Hospital of Hebei Medical University, Shijiazhuang, China.
Xiaohong Wang *Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong-Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong SAR, China.
Shang GuoInstitute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong-Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong SAR, China.
Hongyan GouInstitute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong-Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong SAR, China.ORCID 0000-0002-3446-6402
Haiyun ShangInstitute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong-Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong SAR, China.
Xiaojia JiangInstitute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong-Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong SAR, China.
Chunxian WeiInstitute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong-Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong SAR, China.
Jia WangThe First Hospital of Hebei Medical University, Shijiazhuang, China.
Chao LiDepartments of Endoscopy Center, The First Hospital of Hebei Medical University, Shijiazhuang, China.
Lihong WangThe First Hospital of Hebei Medical University, Shijiazhuang, China.
Zengren ZhaoThe First Hospital of Hebei Medical University, Shijiazhuang, China. zhaozengren@hebmu.edu.cn.ORCID 0000-0002-4802-3581
Weifang YuDepartments of Endoscopy Center, The First Hospital of Hebei Medical University, Shijiazhuang, China. yuweifang@hebmu.edu.cn.
Jun YuInstitute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong-Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong SAR, China. junyu@cuhk.edu.hk.ORCID 0000-0001-5008-2153
Hebei Medical University · CNChinese University of Hong Kong · HK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Copy number alterations are crucial for the development of gastric cancer (GC). Here, we identified Transmembrane Protein 65 (TMEM65) amplification by genomic hybridization microarray to profile copy-number variations in GC. TMEM65 mRNA level was significantly up-regulated in GC compared to adjacent normal tissues, and was positively associated with TMEM65 amplification. High TMEM65 expression or DNA copy number predicts poor prognosis (P < 0.05) in GC. Furtherly, GC patients with TMEM65 amplification (n = 129) or overexpression (n = 78) significantly associated with shortened survival. Ectopic expression of TMEM65 significantly promoted cell proliferation, cell cycle progression and cell migration/invasion ability, but inhibited apoptosis (all P < 0.05). Conversely, silencing of TMEM65 in GC cells showed opposite abilities on cell function in vitro and suppressed tumor growth and lung metastasis in vivo (all P < 0.01). Moreover, TMEM65 depletion by VNP-encapsulated TMEM65-siRNA significantly suppressed tumor growth in subcutaneous xenograft model. Mechanistically, TMEM65 exerted oncogenic effects through activating PI3K-Akt-mTOR signaling pathway, as evidenced of increased expression of key regulators (p-Akt, p-GSK-3β, p-mTOR) by Western blot. YWHAZ (Tyrosine 3-Monooxygenase/Tryptophan 5-Monooxygenase) was identified as a direct downstream effector of TMEM65. Direct binding of TMEM65 with YWHAZ in the cytoplasm inhibited ubiquitin-mediated degradation of YWHAZ. Moreover, oncogenic effect of TMEM65 was partly dependent on YWHAZ. In conclusion, TMEM65 promotes gastric tumorigenesis by activating PI3K-Akt-mTOR signaling via cooperating with YWHAZ. TMEM65 overexpression may serve as an independent new biomarker and is a therapeutic target in GC.

Indexed as

Proto-Oncogene Proteins c-aktStomach Neoplasms14-3-3 ProteinsCarcinogenesisCell Line, TumorCell ProliferationCell Transformation, NeoplasticGlycogen Synthase Kinase 3 betaHumansMembrane ProteinsMitochondrial ProteinsPhosphatidylinositol 3-KinasesTOR Serine-Threonine KinasesTranscription Factors14-3-3 ProteinsGlycogen Synthase Kinase 3 betaMembrane ProteinsMitochondrial ProteinsPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktTMEM65 protein, humanTOR Serine-Threonine KinasesTranscription FactorsYWHAZ protein, human

Identifiers

PMID38341472
PMCPMC10959749
OpenAlexW4391721590

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.