LINC-PINT impedes DNA repair and enhances radiotherapeutic response by targeting DNA-PKcs in nasopharyngeal cancer.

Cell Death & Disease
You-Hong WangWei Zhang

Abstract

Radioresistance continues to be the leading cause of recurrence and metastasis in nasopharyngeal cancer. Long noncoding RNAs are emerging as regulators of DNA damage and radioresistance. LINC-PINT was originally identified as a tumor suppressor in various cancers. In this study, LINC-PINT was significantly downregulated in nasopharyngeal cancer tissues than in rhinitis tissues, and low LINC-PINT expressions showed poorer prognosis in patients who received radiotherapy. We further identified a functional role of LINC-PINT in inhibiting the malignant phenotypes and sensitizing cancer cells to irradiation in vitro and in vivo. Mechanistically, LINC-PINT was responsive to DNA damage, inhibiting DNA damage repair through ATM/ATR-Chk1/Chk2 signaling pathways. Moreover, LINC-PINT increased radiosensitivity by interacting with DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and negatively regulated the expression and recruitment of DNA-PKcs. Therefore, these findings collectively support the possibility that LINC-PINT serves as an attractive target to overcome radioresistance in NPC.

References

Sep 26, 2001·The Journal of Biological Chemistry·S BurmaD J Chen
Apr 18, 2007·The Journal of Cell Biology·Naoya UematsuDavid J Chen
Sep 25, 2008·Nature Reviews. Molecular Cell Biology·Martin F Lavin
Feb 5, 2010·Leukemia·L-J MahT C Karagiannis
Aug 12, 2010·Antioxidants & Redox Signaling·Katherine S PawelczakJohn J Turchi
Jun 6, 2012·Annual Review of Biochemistry·John L Rinn, Howard Y Chang
Nov 24, 2012·Nature Reviews. Cancer·Nicola J Curtin
Nov 26, 2014·Annual Review of Medicine·Michael Goldstein, Michael B Kastan
May 2, 2015·Cancer Research·Anchit Khanna
Sep 10, 2015·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Anne W M LeeAnthony T C Chan
Nov 23, 2015·Molecular Cell·Mark J O'Connor
Dec 17, 2015·Nature Reviews. Genetics·Jeffrey J Quinn, Howard Y Chang
Apr 26, 2016·Nature Structural & Molecular Biology·Youyou ZhangLin Zhang
Oct 28, 2016·Nature Genetics·Adam M SchmittHoward Y Chang
Dec 23, 2016·Nature Cell Biology·Nicole Hustedt, Daniel Durocher
May 18, 2017·Nature Reviews. Molecular Cell Biology·Howard H Y ChangMichael R Lieber
Jun 18, 2017·Molecular Cell·Andrew N Blackford, Stephen P Jackson
Sep 20, 2017·Cell Research·Go WatanabeDewight Williams
Sep 1, 2018·Molecular Cancer Therapeutics·Xinyi TuRobert W Mutter
Oct 24, 2018·International Journal of Cancer. Journal International Du Cancer·J FerlayF Bray
Mar 9, 2019·Molecular Cell·Joana Carlevaro-Fita, Rory Johnson
Jun 11, 2019·Lancet·Yu-Pei ChenJun Ma
Jul 3, 2019·Nature Reviews. Molecular Cell Biology·Ralph ScullyNicholas A Willis

❮ Previous
Next ❯

Citations

Sep 3, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Tiefei HeCansong Zhao

❮ Previous
Next ❯

Software Mentioned

Flowjo
SPSS
LINC
GeneSpring
GraphPad Prism
Image lab
Image J
PINT

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.