Hypoxia induced LUCAT1/PTBP1 axis modulates cancer cell viability and chemotherapy response

Molecular Cancer
Lin HuanXianghuo He

Abstract

Hypoxic tumors are refractory to DNA damage drugs. However, the underlying mechanism has yet to be elucidated. We aimed to identify lncRNAs that upregulated under hypoxia and their effects on colorectal cancer (CRC). CRC cells were treated with 1% O2 to identify lncRNAs that upregulated under hypoxia. We integrated these lncRNAs with RNA-seq of 4 paired CRC tissues and TCGA data to get candidate lncRNAs. Multiple in vitro and in vivo assays were used to explore the role of LUCAT1 in CRC. We identified a hypoxia-induced lncRNA LUCAT1 that facilitated the growth of CRC cells and contributed to drug resistance of CRC cells both in vitro and in vivo. Mechanically, LUCAT1 interacts with polypyrimidine tract binding protein 1 (PTBP1) in CRC cells, facilitates the association of a set of DNA damage related genes with PTBP1, thus resulting in altered alternative splicing of these genes. Moreover, ectopic expression of PTBP1 in CRC cells with knockdown of LUCAT1 abrogated the effects induced by LUCAT1 knockdown. Chemotherapeutics drug combined with LUCAT1 knockdown via antisense oligonucleotides (ASO) would get a better outcome in vivo, compared with group treated with chemotherapeutic drug only. Notably, LUCAT1 is upregulated in CRC ti...Continue Reading

References

Apr 16, 1998·The Journal of Biological Chemistry·E P RogakouW M Bonner
Jun 2, 2004·Nature Reviews. Cancer·J Martin Brown, William R Wilson
Jun 25, 2004·Experimental and Molecular Pathology·Minalini LakshmanSerge Jothy
Jun 10, 2009·Brain : a Journal of Neurology·Hannah C CheungGilbert J Cote
Mar 5, 2011·The Journal of Biological Chemistry·Thorsten JungMargot Zöller
Mar 9, 2012·Trends in Pharmacological Sciences·Gregg L Semenza
Aug 14, 2013·Annual Review of Pathology·Gregg L Semenza
Jan 28, 2014·Journal of Cell Science·Kenji TakahashiTushar Patel
May 16, 2014·Nucleic Acids Research·Inbal PazYael Mandel-Gutfreund
Apr 24, 2015·Molecular Cancer Therapeutics·Hidekazu TakahashiHirofumi Yamamoto
Apr 29, 2015·The Journal of Cell Biology·Yihan WanYixian Zheng
Jul 8, 2015·Oncology Reports·Marina De RosaPaolo Delrio
Nov 6, 2015·Nature Medicine·Maite Huarte
Nov 26, 2015·Nucleic Acids Research·Michael RyanJohn Weinstein
Jun 24, 2017·Nature Communications·Jing-Wen ShihHsing-Jien Kung
Nov 25, 2017·Biochemical and Biophysical Research Communications·Zhe Han, Liying Shi
May 12, 2018·Cell Death & Disease·Jia Cui, William J Placzek
Jul 18, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Pamela BielliClaudio Sette
Aug 16, 2018·Biochemical and Biophysical Research Communications·He YuGuangxin Liu
Sep 20, 2018·World Journal of Gastroenterology : WJG·Kevin Van der JeughtGuang Ji
Dec 28, 2018·Journal of Cellular and Molecular Medicine·Yun LouGuoqiang Li

❮ Previous
Next ❯

Citations

Jul 18, 2020·Journal of Experimental & Clinical Cancer Research : CR·Yonghao ZhanXuepei Zhang
Jan 3, 2021·Cellular and Molecular Life Sciences : CMLS·Subhashis NatuaSanjeev Shukla
Dec 29, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Ce XingFeng Bai
Feb 6, 2021·Future Oncology·Min MaChangwei Lin
Jan 8, 2021·Journal of Experimental & Clinical Cancer Research : CR·Yunze LiuYi Zhang
Mar 7, 2021·International Journal of Molecular Sciences·Maria Magdalena BarrecaAlice Conigliaro
Sep 26, 2020·Biochemical Pharmacology·Ying ZhouLushan Yu
Aug 11, 2021·Cancer Cell International·Qian LuHongming Pan

❮ Previous
Next ❯

Methods Mentioned

BETA
RNA-seq
PCR
reverse transcription PCR
xenograft
pulldown
RIP
immunoprecipitation
pull down

Software Mentioned

ImageJ
RBPmap
metascape
StringTie
RNAfold
GSEA
Integrative Genomics Viewer ( IGV )
GraphPad Prism
clusterProfiler
SPSS

Related Concepts

Related Feeds

Alternative splicing

Alternative splicing a regulated gene expression process that allows a single genetic sequence to code for multiple proteins. Here is that latest research.

Antisense Oligonucleotides: ND

This feed focuses on antisense oligonucleotide therapies such as Inotersen, Nusinursen, and Patisiran, in neurodegenerative diseases including amyotrophic lateral sclerosis.