Evidence map›Paper›PMID 33575113›Full record

ArticleMolecular therapy. Nucleic acids2021

Comprehensive landscape of epigenetic-dysregulated lncRNAs reveals a profound role of enhancers in carcinogenesis in BC subtypes.

Hongying Zhao, Xiaoqin Liu, Lei Yu, Shihua Lin, Caiyu Zhang, Haotian Xu, Zhijun Leng, Waidong Huang, Junjie Lei, Tengyue Li and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular therapy. Nucleic acids, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

38 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  16. Comprehensive analyses of NCancer science · 2022
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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

13 authors.

Hongying ZhaoCollege of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China.
Xiaoqin LiuSchool of Life Sciences, Westlake University, Hangzhou 310024, China.
Lei YuCollege of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China.
Shihua LinCollege of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China.
Caiyu ZhangCollege of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China.
Haotian XuCollege of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China.
Zhijun LengCollege of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China.
Waidong HuangCollege of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China.
Junjie LeiCollege of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China.
Tengyue LiCollege of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China.
Jing LiDepartment of Ultrasonic Medicine, The 1st Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin 150040, China.
Fan YangDepartment of Pharmacology (The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin 150081, China.
Li WangCollege of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Aberrant expression of long non-coding RNAs (lncRNA) is associated with altered DNA methylation and histone modifications during carcinogenesis. However, identifying epigenetically dysregulated lncRNAs and characterizing their functional mechanisms in different cancer subtypes are still major challenges for cancer studies. In this study, we systematically analyzed the epigenetic alterations of lncRNAs at important regulatory elements in three breast cancer subtypes. We identified 87, 691, and 1,197 epigenetically dysregulated lncRNAs in luminal, basal, and claudin-low subtypes of breast cancer, respectively. The landscape of epigenetically dysregulated lncRNAs at enhancer elements revealed that epigenetic changes of the majority of lncRNAs occurred in a subtype-specific manner and contributed to subtype-specific biological functions. We identified six acetylation of lysine 27 on histone H3 (H3K27ac)-dysregulated lncRNAs and three DNA methylation-dysregulated lncRNAs (CTC-303L1.2, RP11-738B7.1, and SLC26A4-AS1) as prognostic biomarkers of basal subtype. These lncRNAs were involved in immune response-related biological functions. Treatment of the basal breast cancer cell line MDA-MB-468 with CREBBP/EP300 bromodomain inhibitors downregulated H3K27 acetylation levels and caused a decrease in the expression of five H3K27ac-dysregulated lncRNAs (LINC00393, KB-1836B5.1, RP1-140K8.5, AC005162.1, and AC020916.2) and inhibition of the growth of breast cancer cells. One epigenetically dysregulated lncRNA (LINC01983) and four lncRNA regulators (UCA1, RP11-221J22.2, RP11-221J22.1, and RP1-212P9.3) were identified as prognostic biomarkers of the luminal molecular subtype of breast cancer by controlling the tumor necrosis factor (TNF) signaling pathway, T helper (Th)17 cell differentiation, and T cell migration. Finally, our results highlighted a profound role of enhancer-related H3K27ac-dysregulated lncRNAs, DNA methylation-dysregulated lncRNAs, and lncRNA regulators in breast cancer subtype carcinogenesis and their potential prognostic value.

Indexed as

breast cancer subtypesenhancerepigeneticslong non-coding RNAsprognostic biomarkers

Identifiers

PMID33575113
PMCPMC7851425

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.