Function of HNRNPC in breast cancer cells by controlling the dsRNA-induced interferon response

The EMBO Journal
Yusheng WuXuerui Yang

Abstract

Elevated expression of RNA binding protein HNRNPC has been reported in cancer cells, while the essentialness and functions of HNRNPC in tumors were not clear. We showed that repression of HNRNPC in the breast cancer cells MCF7 and T47D inhibited cell proliferation and tumor growth. Our computational inference of the key pathways and extensive experimental investigations revealed that the cascade of interferon responses mediated by RIG-I was responsible for such tumor-inhibitory effect. Interestingly, repression of HNRNPC resulted in accumulation of endogenous double-stranded RNA (dsRNA), the binding ligand of RIG-I. These up-regulated dsRNA species were highly enriched by Alu sequences and mostly originated from pre-mRNA introns that harbor the known HNRNPC binding sites. Such source of dsRNA is different than the recently well-characterized endogenous retroviruses that encode dsRNA In summary, essentialness of HNRNPC in the breast cancer cells was attributed to its function in controlling the endogenous dsRNA and the down-stream interferon response. This is a novel extension from the previous understandings about HNRNPC in binding with introns and regulating RNA splicing.

References

May 11, 2000·Molecular and Cellular Biology·D J WilliamsonH E Ruley
Jul 23, 2003·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Irene PinoLuis M Montuenga
May 3, 2005·Nature Reviews. Immunology·Leonidas C Platanias
Jul 14, 2005·Molecular and Cellular Biochemistry·Sreerama Shetty
Mar 29, 2006·Cellular and Molecular Life Sciences : CMLS·P Svoboda, A Di Cara
Dec 13, 2006·The EMBO Journal·Bert SchepensSigrid Cornelis
Apr 5, 2007·Nature Protocols·Adam A MargolinAndrea Califano
May 19, 2007·The EMBO Journal·Yoon Ki KimLynne E Maquat
May 22, 2007·Cellular and Molecular Life Sciences : CMLS·J HäslerK Strub
Dec 9, 2008·Nature Structural & Molecular Biology·Andrea B EberleTorben Heick Jensen
Dec 17, 2008·Annals of the New York Academy of Sciences·Taro Kawai, Shizuo Akira
May 18, 2010·Nature Structural & Molecular Biology·Eun Kyung LeeMyriam Gorospe
Jun 29, 2010·Nature Structural & Molecular Biology·Yanli WangDinshaw J Patel
Jul 6, 2010·Nature Structural & Molecular Biology·Julian KönigJernej Ule
Sep 2, 2010·Proceedings of the National Academy of Sciences of the United States of America·Alina BaumAdolfo García-Sastre
Oct 29, 2010·Genome Biology·Simon Anders, Wolfgang Huber
Feb 8, 2011·Nature·Hiroki KanekoJayakrishna Ambati
Dec 30, 2011·Genome Biology·Prescott Deininger
Feb 11, 2012·Critical Reviews in Immunology·Uma Nagarajan
Jun 23, 2012·Genome Research·Simon AndersWolfgang Huber
Sep 8, 2012·Genome Research·Jennifer HarrowTim J Hubbard
Nov 7, 2012·Proceedings of the National Academy of Sciences of the United States of America·Alys PeisleySun Hur
Dec 14, 2012·Proceedings of the National Academy of Sciences of the United States of America·Katerina I LeonovaAndrei V Gudkov
May 28, 2013·Immunity·Delphine GoubauCaetano Reis e Sousa
Aug 27, 2013·FEBS Letters·Feng YangZicai Liang
Dec 24, 2013·Nature Reviews. Immunology·Lionel B Ivashkiv, Laura T Donlin
Jan 24, 2014·Nucleic Acids Research·Janina E Moretti, Ulrich F Müller

❮ Previous
Next ❯

Citations

Nov 6, 2018·The EMBO Journal·Stephanie L SarbanesCharles M Rice
Sep 29, 2019·Journal of Molecular Cell Biology·Antonella Di LiddoKathi Zarnack
Nov 2, 2019·Oncotarget·Esmee KoedootSylvia E Le Dévédec
Apr 3, 2020·Combinatorial Chemistry & High Throughput Screening·Zhongqiu LiQiao Zhang
Oct 23, 2019·Journal of Cellular Physiology·Shuting ZhangJie Cheng
Nov 30, 2019·Journal of Experimental & Clinical Cancer Research : CR·Mingxia YanMing Yao
Jul 13, 2020·Journal of Hematology & Oncology·Hai QinLufeng Zheng
Jan 20, 2021·Cellular & Molecular Immunology·Koji OnomotoMitsutoshi Yoneyama
Jan 16, 2021·Viruses·Justine LagisquetThomas Gramberg
Dec 10, 2020·Cell & Bioscience·Yanyan WangSuzhan Zhang
Feb 3, 2021·Journal of Experimental & Clinical Cancer Research : CR·Yi ZhangPengyuan Liu
Feb 27, 2021·Frontiers in Immunology·Haruna OkudeTaro Kawai
May 1, 2021·Life·Roberto FerrariGiorgio Dieci
May 18, 2021·Neoplasia : an International Journal for Oncology Research·Runping FangHui Shi
Jul 24, 2021·The Journal of Experimental Medicine·Anna-Maria HerznerMatthew L Albert
Jul 16, 2020·Immunity·GuanQun Liu, Michaela U Gack
Aug 19, 2021·Immunological Reviews·Nandan S GokhaleRam Savan

❮ Previous
Next ❯

Datasets Mentioned

BETA
GSE100451

Methods Mentioned

BETA
transfection
xenograft
transfections
pull down
pulled down
phosphotransferases
gene
protein assay
ELISA
immunoprecipitation

Software Mentioned

dexseq
MARINa
Cutadapt
DAVID
ARACNe
DESeq2
MARINa MAster Regulator INference
Perl script
RepeatMasker
bowtie2

Related Concepts

Related Feeds

Breast Tumorigenesis

Breast tumorigenesis involves the production or formation of tumor(s) in breast tissue. Discover the latest research on breast tumorigenesis here.