Evidence map›Paper›PMID 32341332›Full record

ArticleCell death & disease2020

Chidamide epigenetically represses autophagy and exerts cooperative antimyeloma activity with bortezomib.

Li Xu, Juan Feng, Hailong Tang, Ying Dong, Mimi Shu, Xiequn Chen

Open access · goldAbstract read
In one paragraph

Article in Cell death & disease, 2020. 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
0.6field-weighted citation impact, top 35% 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, 23 citations in OpenAlex.

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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 2 institutions in 1 country.

Li Xu *Department of Hematology, Xijing Hospital, Fourth Military Medical University, Xian, 710032, Shaanxi, China.
Juan Feng *Department of Hematology, Xijing Hospital, Fourth Military Medical University, Xian, 710032, Shaanxi, China.
Hailong Tang *Department of Hematology, Xijing Hospital, Fourth Military Medical University, Xian, 710032, Shaanxi, China.
Ying DongDepartment of Hematology, Xijing Hospital, Fourth Military Medical University, Xian, 710032, Shaanxi, China.
Mimi ShuDepartment of Hematology, Xijing Hospital, Fourth Military Medical University, Xian, 710032, Shaanxi, China. shummi@fmmu.edu.cn.
Xiequn ChenDepartment of Hematology, Xijing Hospital, Fourth Military Medical University, Xian, 710032, Shaanxi, China. xiequnchen@fmmu.edu.cn.ORCID http://orcid.org/0000-0002-9848-7894
Xijing Hospital · CNNorthwest University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Autophagy and ubiquitin proteasome system are two distinct and cooperative proteolytic pathways. The dual-pathway suppression represents a promising therapeutic strategy for multiple myeloma. Chidamide is a novel benzamide inhibitor of histone deacetylase, and shows potent antimyeloma activity. Here, we revealed the autophagy-suppressive role of chidamide in myeloma cells. We then demonstrated that chidamide treatment markedly downregulated histone deacetylase SIRT1, and simultaneously resulted in dose-dependent upregulation of acetyltransferase hMOF and histone methyltransferase EZH2, which contributed to an increase in global levels of histone H4 lysine 16 acetylation (H4k16ac) and histone H3 lysine 27 trimethylation (H3k27me3). We next confirmed concomitant upregulation of H4k16ac and H3k27me3 in the same promoter regions of the autophagy-related gene LC3B, reinforcing the specific roles for H4k16ac and H3k27me3 in mediating chidamide-induced transcriptional repression of LC3B. Finally, we provided experimental evidence that co-treatment with chidamide and proteasome inhibitor bortezomib induced clear synergistic cytotoxicity against MM cells, which was associated with increased accumulation of ubiquitinated proteins and excessive endoplasmic reticulum stress or dysregulated unfolded protein response. Our results altogether suggest that chidamide cooperatively potentiates antimyeloma activity of bortezomib, at least in part, by epigenetically repressing autophagic degradation of ubiquitinated proteins.

Indexed as

AminopyridinesAnimalsAntineoplastic AgentsAutophagyBenzamidesBortezomibCell Culture TechniquesCell Line, TumorEpigenomicsFemaleHistone DeacetylasesHumansMiceMice, NudeMicroscopy, Electron, TransmissionMultiple MyelomaAminopyridinesAntineoplastic AgentsBenzamidesBortezomibHistone DeacetylasesN-(2-amino-5-fluorobenzyl)-4-(N-(pyridine-3-acrylyl)aminomethyl)benzamide

Identifiers

PMID32341332
PMCPMC7186232
OpenAlexW3019833574

What OpenQuestion holds

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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.