Exploring the major cross-talking edges of competitive endogenous RNA networks in human Chronic and Acute Myeloid Leukemia

Kamalika Sen; Dhananjay Bhattacharyya; Arijita Sarkar; Jyotirmoy Das; Nilanjana Maji; Moitri Basu; Zhumur Ghosh; Tapash Chandra Ghosh

doi:10.1016/j.bbagen.2018.06.002

Exploring the major cross-talking edges of competitive endogenous RNA networks in human Chronic and Acute Myeloid Leukemia

Biochim Biophys Acta Gen Subj. 2018 Sep;1862(9):1883-1892. doi: 10.1016/j.bbagen.2018.06.002. Epub 2018 Jun 15.

Authors

Kamalika Sen¹, Dhananjay Bhattacharyya², Arijita Sarkar³, Jyotirmoy Das⁴, Nilanjana Maji⁵, Moitri Basu⁶, Zhumur Ghosh⁷, Tapash Chandra Ghosh⁸

Affiliations

¹ Bioinformatics Centre, Bose Institute, Kolkata 700 054, India. Electronic address: kamlika@jcbose.ac.in.
² Computational Science Division, Saha Institute of Nuclear Physics, Kolkata 700 064, India. Electronic address: dhananjay.bhattacharyya@saha.ac.in.
³ Bioinformatics Centre, Bose Institute, Kolkata 700 054, India. Electronic address: arijita@jcbose.ac.in.
⁴ Department of Clinical and Experimental Medicine, Faculty of Medicine and Health Sciences, Linköping University, 581 83 Linköping, Sweden. Electronic address: jyotirmoy.das@liu.se.
⁵ Department of Biophysics, Bose Institute, Kolkata 700 054, India. Electronic address: nilanjana@jcbose.ac.in.
⁶ Department of Biophysics, Bose Institute, Kolkata 700 054, India. Electronic address: moitrri.basu@jcbose.ac.in.
⁷ Bioinformatics Centre, Bose Institute, Kolkata 700 054, India. Electronic address: zhumur@jcbose.ac.in.
⁸ Bioinformatics Centre, Bose Institute, Kolkata 700 054, India. Electronic address: tapash@jcbose.ac.in.

PMID: 29902552
DOI: 10.1016/j.bbagen.2018.06.002

Abstract

Background: Human Chronic and Acute Myeloid Leukemia are myeloproliferative disorders in myeloid lineage of blood cells characterized by accumulation of aberrant white blood cells. In cancer, the anomalous transcriptome includes deregulated expression of non-coding RNAs in conjunction with protein-coding mRNAs in human genome. The coding or non-coding RNA transcripts harboring miRNA-binding sites can converse with and regulate each other by explicitly contending for a limited pool of shared miRNAs and act as competitive endogenous RNAs (ceRNAs). An unifying hypothesis attributing 'modulation of expression of transcripts' in this fashion had been defined as 'competitive endogenous RNA hypothesis'. Network built with ceRNAs evidently offers a platform to elucidate complex regulatory interactions at post-transcriptional level in human cancers.

Methods: Contemplating cancers of human myeloid lineage we constructed ceRNA networks for CML and AML coding and non-coding repertoire utilizing patient sample data. Through functional enrichment analysis we selected the significant functional modules for transcripts being differentially expressed in Blastic phases of each cancer types with respect to Normal. After retrieving free energy of binding and duplex formation of shared miRNAs on ceRNAs, we performed statistical averaging of energy values over the ensemble of populations considering cellular system as in canonical (Iso-thermal) situation.

Results and conclusions: We aimed to shed light on 'Sibling Rivalry' in ceRNA partners from the perspective of statistical thermodynamics, identified major cross-talking tracks and ceRNAs influencing transcripts concerned in myeloid cancer systems.

General significance: Insights into ceRNA-regulation will shed light on progression and prognosis of human Chronic and Acute Myeloid Leukemia.

Keywords: Competitive binding; Functional enrichment; Statistical thermodynamics; miRNA:mRNA binding energy; microRNA; microRNA sponging effect.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers, Tumor / genetics*
Case-Control Studies
Databases, Factual
Gene Expression Regulation, Neoplastic
Gene Regulatory Networks*
High-Throughput Nucleotide Sequencing / methods
Humans
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics*
Leukemia, Myeloid, Acute / genetics*
MicroRNAs / genetics*
RNA, Long Noncoding / genetics*
RNA, Messenger / genetics*
Transcriptome

Substances

Biomarkers, Tumor
MicroRNAs
RNA, Long Noncoding
RNA, Messenger