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

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.Funding Agencies|Science and Engineering Research Board, Department of Science and Technology, Govt. of India [YSS/2015/000115]</p

Solvent adaptive dynamic metal-organic soft hybrid for imaging and biological delivery

A solvent responsive dynamic nanoscale metal‐organic framework (NMOF) [Zn(1 a)(H$_2$O)$_2$] has been devised based on the self‐assembly of Zn$^{II}$ and asymmetric bola‐amphiphilic oligo‐(p‐phenyleneethynylene) (OPE) dicarboxylate linker 1 a having dodecyl and triethyleneglycolmonomethylether (TEG, polar) side chains. In THF solvent, NMOF showed nanovesicular morphology (NMOF‐1) with surface decorated dodecyl chains. In water and methanol, NMOF exhibited inverse‐nanovesicle (NMOF‐2) and nanoscroll (NMOF‐3) morphology, respectively, with surface projected TEG chains. The pre‐formed NMOFs also unveiled reversible solvent responsive transformation of different morphologies. The flexible NMOF showed cyan emission and no cytotoxicity, allowing live cell imaging. Cisplatin (14.4 wt %) and doxorubicin (4.1 wt %) were encapsulated in NMOF‐1 by non‐covalent interactions and, in vitro and in vivo drug release was studied. The drug loaded NMOFs exhibited micromolar cytotoxicity