NDLI: Towards resolution of the intron retention paradox in breast cancer

Content Provider	Springer Nature : BioMed Central
Author	Shah, Jaynish S. Milevskiy, Michael J. G. Petrova, Veronika Au, Amy Y. M. Wong, Justin J. L. Visvader, Jane E. Schmitz, Ulf Rasko, John E. J.
Abstract	Background After many years of neglect in the field of alternative splicing, the importance of intron retention (IR) in cancer has come into focus following landmark discoveries of aberrant IR patterns in cancer. Many solid and liquid tumours are associated with drastic increases in IR, and such patterns have been pursued as both biomarkers and therapeutic targets. Paradoxically, breast cancer (BrCa) is the only tumour type in which IR is reduced compared to adjacent normal breast tissue. Methods In this study, we have conducted a pan-cancer analysis of IR with emphasis on BrCa and its subtypes. We explored mechanisms that could cause aberrant and pathological IR and clarified why normal breast tissue has unusually high IR. Results Strikingly, we found that aberrantly decreasing IR in BrCa can be largely attributed to normal breast tissue having the highest occurrence of IR events compared to other healthy tissues. Our analyses suggest that low numbers of IR events in breast tumours are associated with poor prognosis, particularly in the luminal B subtype. Interestingly, we found that IR frequencies negatively correlate with cell proliferation in BrCa cells, i.e. rapidly dividing tumour cells have the lowest number of IR events. Aberrant RNA-binding protein expression and changes in tissue composition are among the causes of aberrantly decreasing IR in BrCa. Conclusions Our results suggest that IR should be considered for therapeutic manipulation in BrCa patients with aberrantly low IR levels and that further work is needed to understand the cause and impact of high IR in other tumour types.
Related Links	https://breast-cancer-research.biomedcentral.com/counter/pdf/10.1186/s13058-022-01593-1.pdf
Ending Page	11
Page Count	11
Starting Page	1
File Format	HTM / HTML
DOI	10.1186/s13058-022-01593-1
Journal	Breast Cancer Research
Issue Number	1
Volume Number	24
Language	English
Publisher	BioMed Central
Publisher Date	2022-12-29
Access Restriction	Open
Subject Keyword	Cancer Research Oncology Surgical Oncology Alternative splicing Patient stratification Luminal B breast cancer Adipocytes Cancer transcriptomics
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology
Journal Impact Factor	6.1/2023
5-Year Journal Impact Factor	7.1/2023

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Towards resolution of the intron retention paradox in breast cancer

Splicing targeting drugs highlight intron retention as an actionable vulnerability in advanced prostate cancer

Alternative splicing of CERS2 promotes cell proliferation and migration in luminal B subtype breast cancer cells.

Comprehensive splicing functional analysis of DNA variants of the BRCA2 gene by hybrid minigenes

Getting deep in the luminal B breast cancer subtype and its ki67 cut-off value

Prognostic parameters of luminal A and luminal B intrinsic breast cancer subtypes of Pakistani patients

Translational breast cancer research in luminal breast cancer

Splicing factors control triple-negative breast cancer cell mitosis through SUN2 interaction and sororin intron retention

Genes harbouring susceptibility SNPs are differentially expressed in the breast cancer subtypes

Towards resolution of the intron retention paradox in breast cancer

Similar Documents

Towards resolution of the intron retention paradox in breast cancer

Splicing targeting drugs highlight intron retention as an actionable vulnerability in advanced prostate cancer

Alternative splicing of CERS2 promotes cell proliferation and migration in luminal B subtype breast cancer cells.

Comprehensive splicing functional analysis of DNA variants of the BRCA2 gene by hybrid minigenes

Getting deep in the luminal B breast cancer subtype and its ki67 cut-off value

Prognostic parameters of luminal A and luminal B intrinsic breast cancer subtypes of Pakistani patients

Translational breast cancer research in luminal breast cancer

Splicing factors control triple-negative breast cancer cell mitosis through SUN2 interaction and sororin intron retention

Genes harbouring susceptibility SNPs are differentially expressed in the breast cancer subtypes

Towards resolution of the intron retention paradox in breast cancer