PMID- 32844230
OWN - NLM
STAT- MEDLINE
DCOM- 20211115
LR  - 20240216
IS  - 1477-4054 (Electronic)
IS  - 1467-5463 (Print)
IS  - 1467-5463 (Linking)
VI  - 22
IP  - 3
DP  - 2021 May 20
TI  - The microRNA target site landscape is a novel molecular feature associating 
      alternative polyadenylation with immune evasion activity in breast cancer.
LID - 10.1093/bib/bbaa191 [doi]
LID - bbaa191
AB  - Alternative polyadenylation (APA) in breast tumor samples results in the 
      removal/addition of cis-regulatory elements such as microRNA (miRNA) target sites 
      in the 3'-untranslated region (3'-UTRs) of genes. Although previous computational 
      APA studies focused on a subset of genes strongly affected by APA (APA genes), we 
      identify miRNAs of which widespread APA events collectively increase or decrease 
      the number of target sites [probabilistic inference of microRNA target site 
      modification through APA (PRIMATA-APA)]. Using PRIMATA-APA on the cancer genome 
      atlas (TCGA) breast cancer data, we found that the global APA events change the 
      number of the target sites of particular microRNAs [target sites modified miRNA 
      (tamoMiRNA)] enriched for cancer development and treatments. We also found that 
      when knockdown (KD) of NUDT21 in HeLa cells induces a different set of widespread 
      3'-UTR shortening than TCGA breast cancer data, it changes the target sites of 
      the common tamoMiRNAs. Since the NUDT21 KD experiment previously demonstrated the 
      tumorigenic role of APA events in a miRNA dependent fashion, this result suggests 
      that the APA-initiated tumorigenesis is attributable to the miRNA target site 
      changes, not the APA events themselves. Further, we found that the miRNA target 
      site changes identify tumor cell proliferation and immune cell infiltration to 
      the tumor microenvironment better than the miRNA expression levels or the APA 
      events themselves. Altogether, our computational analyses provide a 
      proof-of-concept demonstration that the miRNA target site information indicates 
      the effect of global APA events with a potential as predictive biomarker.
CI  - (c) The Author(s) 2020. Published by Oxford University Press. All rights reserved. 
      For Permissions, please email: journals.permissions@oup.com.
FAU - Kim, Soyeon
AU  - Kim S
AD  - Department of Pediatrics, University of Pittsburgh Medical Center and in Division 
      of Pulmonary Medicine, Children's Hospital of Pittsburgh of UPMC.
FAU - Bai, YuLong
AU  - Bai Y
AD  - Department of Human Genetics in the Graduate School of Public Health, University 
      of Pittsburgh.
FAU - Fan, Zhenjiang
AU  - Fan Z
AD  - Department of Computer Science, University of Pittsburgh.
FAU - Diergaarde, Brenda
AU  - Diergaarde B
AD  - Department of Human Genetics, Graduate School of Public Health, University of 
      Pittsburgh.
FAU - Tseng, George C
AU  - Tseng GC
AD  - Department of Biostatistics, Graduate School of Public Health, University of 
      Pittsburgh.
FAU - Park, Hyun Jung
AU  - Park HJ
AUID- ORCID: 0000-0002-8324-2624
AD  - Department of Human Genetics, Graduate School of Public Health, University of 
      Pittsburgh.
LA  - eng
GR  - P30 CA047904/CA/NCI NIH HHS/United States
GR  - UL1 TR001857/TR/NCATS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Brief Bioinform
JT  - Briefings in bioinformatics
JID - 100912837
RN  - 0 (3' Untranslated Regions)
RN  - 0 (Cleavage And Polyadenylation Specificity Factor)
RN  - 0 (MicroRNAs)
RN  - 0 (Nudt21 protein, human)
SB  - IM
MH  - 3' Untranslated Regions/*genetics
MH  - Algorithms
MH  - Binding Sites/genetics
MH  - Breast Neoplasms/*genetics/metabolism
MH  - Cell Proliferation/genetics
MH  - Cleavage And Polyadenylation Specificity Factor/genetics/metabolism
MH  - Gene Expression Regulation, Neoplastic
MH  - HeLa Cells
MH  - Humans
MH  - MicroRNAs/*genetics
MH  - Models, Genetic
MH  - Polyadenylation/*genetics
MH  - RNA-Seq/methods
MH  - Tumor Escape/*genetics
MH  - Tumor Microenvironment/genetics
PMC - PMC8138879
OTO - NOTNLM
OT  - cancer
OT  - microRNA
OT  - posttranscriptional regulation
OT  - tumor heterogeneity
EDAT- 2020/08/28 06:00
MHDA- 2021/11/16 06:00
PMCR- 2021/08/26
CRDT- 2020/08/27 06:00
PHST- 2020/05/21 00:00 [received]
PHST- 2020/07/10 00:00 [revised]
PHST- 2020/07/28 00:00 [accepted]
PHST- 2020/08/28 06:00 [pubmed]
PHST- 2021/11/16 06:00 [medline]
PHST- 2020/08/27 06:00 [entrez]
PHST- 2021/08/26 00:00 [pmc-release]
AID - 5897059 [pii]
AID - bbaa191 [pii]
AID - 10.1093/bib/bbaa191 [doi]
PST - ppublish
SO  - Brief Bioinform. 2021 May 20;22(3):bbaa191. doi: 10.1093/bib/bbaa191.