PMID- 34993232
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220108
IS  - 2296-889X (Print)
IS  - 2296-889X (Electronic)
IS  - 2296-889X (Linking)
VI  - 8
DP  - 2021
TI  - miRNA Combinatorics and its Role in Cell State Control-A Probabilistic Approach.
PG  - 772852
LID - 10.3389/fmolb.2021.772852 [doi]
LID - 772852
AB  - A hallmark of cancer evolution is that the tumor may change its cell identity and 
      improve its survival and fitness. Drastic change in microRNA (miRNA) composition 
      and quantities accompany such dynamic processes. Cancer samples are composed of 
      cells' mixtures of varying stages of cancerous progress. Therefore, cell-specific 
      molecular profiling represents cellular averaging. In this study, we consider the 
      degree to which altering miRNAs composition shifts cell behavior. We used COMICS, 
      an iterative framework that simulates the stochastic events of miRNA-mRNA 
      pairing, using a probabilistic approach. COMICS simulates the likelihood that 
      cells change their transcriptome following many iterations (100 k). Results of 
      COMICS from the human cell line (HeLa) confirmed that most genes are resistant to 
      miRNA regulation. However, COMICS results suggest that the composition of the 
      abundant miRNAs dictates the nature of the cells (across three cell lines) 
      regardless of its actual mRNA steady-state. In silico perturbations of cell lines 
      (i.e., by overexpressing miRNAs) allowed to classify genes according to their 
      sensitivity and resilience to any combination of miRNA perturbations. Our results 
      expose an overlooked quantitative dimension for a set of genes and miRNA 
      regulation in living cells. The immediate implication is that even relatively 
      modest overexpression of specific miRNAs may shift cell identity and impact 
      cancer evolution.
CI  - Copyright (c) 2021 Mahlab-Aviv, Linial and Linial.
FAU - Mahlab-Aviv, Shelly
AU  - Mahlab-Aviv S
AD  - The Rachel and Selim Benin School of Computer Science and Engineering, The Hebrew 
      University of Jerusalem, Jerusalem, Israel.
FAU - Linial, Nathan
AU  - Linial N
AD  - The Rachel and Selim Benin School of Computer Science and Engineering, The Hebrew 
      University of Jerusalem, Jerusalem, Israel.
FAU - Linial, Michal
AU  - Linial M
AD  - Department of Biological Chemistry, Institute of Life Sciences, The Hebrew 
      University of Jerusalem, Jerusalem, Israel.
LA  - eng
PT  - Journal Article
DEP - 20211221
PL  - Switzerland
TA  - Front Mol Biosci
JT  - Frontiers in molecular biosciences
JID - 101653173
PMC - PMC8724548
OTO - NOTNLM
OT  - CLIP-Seq
OT  - Markov chain
OT  - TargetScan
OT  - ceRNA
OT  - cell line
OT  - cell simulation
OT  - miRNA binding site
OT  - miRNA-target prediction
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/01/08 06:00
MHDA- 2022/01/08 06:01
PMCR- 2021/01/01
CRDT- 2022/01/07 06:29
PHST- 2021/09/08 00:00 [received]
PHST- 2021/11/29 00:00 [accepted]
PHST- 2022/01/07 06:29 [entrez]
PHST- 2022/01/08 06:00 [pubmed]
PHST- 2022/01/08 06:01 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 772852 [pii]
AID - 10.3389/fmolb.2021.772852 [doi]
PST - epublish
SO  - Front Mol Biosci. 2021 Dec 21;8:772852. doi: 10.3389/fmolb.2021.772852. 
      eCollection 2021.