Evidence map›Paper›PMID 31347685›Full record

ArticleBrain : a journal of neurology2019

Acquired temozolomide resistance in MGMT-deficient glioblastoma cells is associated with regulation of DNA repair by DHC2.

Guo-Zhong Yi, Guanglong Huang, Manlan Guo, Xi'an Zhang, Hai Wang, Shengze Deng, Yaomin Li, Wei Xiang, Ziyang Chen, Jun Pan and 5 more

Open access · hybridAbstract read
In one paragraph

Article in Brain : a journal of neurology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.

0numbers the graph read from it
0cells of the map it votes in
83citing papers in PubMed
19.3field-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

83 citing papers in PubMed, 181 citations in OpenAlex.

  1. Article
  2. Tumor-intrinsic TLR4 signaling as a context-dependent rheostat in glioblastoma.Journal of molecular medicine (Berlin, Germany) · 2026
    Review
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23 more citing papers are in PubMed but not listed here.

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

15 authors at 4 institutions in 1 country.

Guo-Zhong YiDepartment of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong, People's Republic of China.
Guanglong HuangDepartment of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong, People's Republic of China.
Manlan GuoThe Laboratory for Precision Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong, People's Republic of China.
Xi'an ZhangDepartment of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong, People's Republic of China.
Hai WangDepartment of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong, People's Republic of China.
Shengze DengDepartment of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong, People's Republic of China.
Yaomin LiDepartment of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong, People's Republic of China.
Wei XiangDepartment of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong, People's Republic of China.
Ziyang ChenDepartment of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong, People's Republic of China.
Jun PanDepartment of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong, People's Republic of China.
Zhiyong LiDepartment of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong, People's Republic of China.
Lei YuDepartment of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong, People's Republic of China.
Bingxi LeiDepartment of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong, People's Republic of China.
Yawei LiuThe Laboratory for Precision Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong, People's Republic of China.
Songtao QiDepartment of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong, People's Republic of China.
Nanfang Hospital · CNSouthern Medical University · CNLonggang Central Hospital · CNSouthwest Medical University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The acquisition of temozolomide resistance is a major clinical challenge for glioblastoma treatment. Chemoresistance in glioblastoma is largely attributed to repair of temozolomide-induced DNA lesions by O6-methylguanine-DNA methyltransferase (MGMT). However, some MGMT-deficient glioblastomas are still resistant to temozolomide, and the underlying molecular mechanisms remain unclear. We found that DYNC2H1 (DHC2) was expressed more in MGMT-deficient recurrent glioblastoma specimens and its expression strongly correlated to poor progression-free survival in MGMT promotor methylated glioblastoma patients. Furthermore, silencing DHC2, both in vitro and in vivo, enhanced temozolomide-induced DNA damage and significantly improved the efficiency of temozolomide treatment in MGMT-deficient glioblastoma. Using a combination of subcellular proteomics and in vitro analyses, we showed that DHC2 was involved in nuclear localization of the DNA repair proteins, namely XPC and CBX5, and knockdown of either XPC or CBX5 resulted in increased temozolomide-induced DNA damage. In summary, we identified the nuclear transportation of DNA repair proteins by DHC2 as a critical regulator of acquired temozolomide resistance in MGMT-deficient glioblastoma. Our study offers novel insights for improving therapeutic management of MGMT-deficient glioblastoma.

Indexed as

AnimalsAntineoplastic Agents, AlkylatingBrain NeoplasmsChromobox Protein Homolog 5Cytoplasmic DyneinsDNA Modification MethylasesDNA RepairDNA Repair EnzymesDrug Resistance, NeoplasmGlioblastomaHeterograftsHumansMiceTemozolomideTumor Suppressor ProteinsAntineoplastic Agents, AlkylatingCBX5 protein, humanChromobox Protein Homolog 5Cytoplasmic DyneinsDNA Modification MethylasesDNA Repair EnzymesDYNC2H1 protein, humanMGMT protein, humanTemozolomideTumor Suppressor Proteinsacquired TMZ resistanceCBX5DHC2glioblastomaXPC

Identifiers

PMID31347685
PMCPMC6658867
OpenAlexW2963466627

What OpenQuestion holds

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LicenceCC BY-NC
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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.