XLF-mediated NHEJ activity in hepatocellular carcinoma therapy resistance

BMC Cancer
Sitian Yang, Xiao Qi Wang

Abstract

DNA repair pathways are used by cancer cells to overcome many standard anticancer treatments, causing therapy resistance. Here, we investigated the role of XRCC4-like factor (XLF), a core member of the non-homologous end joining (NHEJ) repair pathway, in chemoresistance in hepatocellular carcinoma (HCC). qRT-PCR analysis and western blotting were performed to detect expression levels of genes and proteins related to NHEJ. NHEJ repair capacity was assessed in vitro (cell-free) and in vivo by monitoring the activity of the NHEJ pathway. Cell viability and IC50 assays were used to measure sensitivity to drug therapy. A xenograft HCC model was used to develop methods of targeting XLF-induced chemosensitization. Clinicopathological analysis was conducted on patients with HCC treated with transarterial chemoembolization (TACE). Many conventional cancer chemotherapeutics induce DNA double-strand breaks (DSBs). HCC cells respond to these breaks by increasing their NHEJ activity, resulting in resistance. XLF-knockdown cells show an inhibition of NHEJ activity in both cell-free and live-cell assays as well as a high level of unrepaired cellular DSBs. These results indicate that XLF facilitates DNA end-joining and therefore promotes NHEJ ...Continue Reading

References

Sep 9, 1999·The Journal of Cell Biology·E P RogakouW M Bonner
Sep 8, 2006·The New England Journal of Medicine·Ken A OlaussenUNKNOWN IALT Bio Investigators
May 2, 2007·Proceedings of the National Academy of Sciences of the United States of America·Chun J TsaiGilbert Chu
Feb 8, 2008·Nature Reviews. Cancer·Thomas HelledayRicky A Sharma
Feb 12, 2008·Nature·Stacey L EdwardsAlan Ashworth
Sep 9, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Ruth Plummer
Jan 25, 2011·Current Opinion in Genetics & Development·Rachel BroughAlan Ashworth
Dec 27, 2011·Cancer Letters·Alesia IvashkevichOlga A Martin
Aug 25, 2012·Nature Reviews. Cancer·Peter Bouwman, Jos Jonkers
Oct 12, 2012·Nature Reviews. Cancer·Peter ValentConnie Eaves
Feb 28, 2013·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Brandi L MahaneySusan P Lees-Miller
Apr 4, 2013·Science Signaling·Jianjiong GaoNikolaus Schultz
Sep 26, 2013·Nature Reviews. Cancer·Caitriona HolohanPatrick G Johnston
Sep 28, 2013·Nature Genetics·UNKNOWN Cancer Genome Atlas Research NetworkJoshua M Stuart
Jan 28, 2014·DNA Repair·Farjana Jahan FattahEric A Hendrickson
Mar 13, 2014·Biomarkers : Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals·Stamatia Pouliliou, Michael I Koukourakis
May 7, 2014·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Sung-Min AhnGu Kong
Jun 3, 2014·BMC Developmental Biology·Xiao Qi WangRonnie T P Poon
Aug 28, 2014·The FEBS Journal·Selcuk Colak, Jan P Medema
Dec 7, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Liam CornellHelen L Reeves
Feb 25, 2015·Nature Reviews. Cancer·Laurence H PearlFrances M G Pearl
Jun 24, 2015·Molecular and Cellular Biology·Sunetra RoyKatheryn Meek
Oct 30, 2016·Annals of Oncology : Official Journal of the European Society for Medical Oncology·K A Olaussen, S Postel-Vinay

❮ Previous
Next ❯

Citations

Apr 7, 2018·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Jorge A MarreroJulie K Heimbach
Jun 27, 2020·Cancers·Jose J G MarinOscar Briz
Nov 17, 2020·Frontiers in Molecular Biosciences·Mohit AroraShyam S Chauhan
Apr 1, 2021·Trends in Genetics : TIG·Dipayan Ghosh, Sathees C Raghavan
Aug 28, 2021·Journal of Experimental & Clinical Cancer Research : CR·Vera Miranda-GonçalvesCarmen Jerónimo
Sep 21, 2021·Seminars in Liver Disease·Jose J G MarinOscar Briz

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR
flow cytometry
xenograft
transfection
xenografts

Software Mentioned

SPSS
GraphPad

Related Concepts

Related Feeds

Carcinoma, Hepatocellular

Hepatocellular Carcinoma is a malignant cancer in liver epithelial cells. Discover the latest research on Hepatocellular Carcinoma here.

Cancer Genomics (Keystone)

Cancer genomics approaches employ high-throughput technologies to identify the complete catalog of somatic alterations that characterize the genome, transcriptome and epigenome of cohorts of tumor samples. Discover the latest research using such technologies in this feed.