PLoS ONE (Jan 2022)

Effects of autophagy modulators tamoxifen and chloroquine on the expression profiles of long non-coding RNAs in MIAMI cells exposed to IFNγ

  • Rajkaran Banga,
  • Veerkaran Banga,
  • Amr Eltalla,
  • Lauren Shahin,
  • Sonam Parag,
  • Maha Naim,
  • Easha Iyer,
  • Neha Kumrah,
  • Brian Zacharias,
  • Lubov Nathanson,
  • Vladimir Beljanski

Journal volume & issue
Vol. 17, no. 4

Abstract

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Mesenchymal stromal cells (MSCs) can be utilized clinically for treatment of conditions that result from excessive inflammation. In a pro-inflammatory environment, MSCs adopt an anti-inflammatory phenotype resulting in immunomodulation. A sub-type of MSCs referred to as “marrow-isolated adult multilineage inducible” (MIAMI) cells, which were isolated from bone marrow, were utilized to show that the addition of autophagy modulators, tamoxifen (TX) or chloroquine (CQ), can alter how MIAMI cells respond to IFNγ exposure in vitro resulting in an increased immunoregulatory capacity of the MIAMI cells. Molecularly, it was also shown that TX and CQ each alter both the levels of immunomodulatory genes and microRNAs which target such genes. However, the role of other non-coding RNAs (ncRNAs) such as long non-coding RNAs (lncRNAs) in regulating the response of MSCs to inflammation has been poorly studied. Here, we utilized transcriptomics and data mining to analyze the putative roles of various differentially regulated lncRNAs in MIAMI cells exposed to IFNγ with (or without) TX or CQ. The aim of this study was to investigate how the addition of TX and CQ alters lncRNA levels and evaluate how such changes could alter previously observed TX- and CQ-driven changes to the immunomodulatory properties of MIAMI cells. Data analysis revealed 693 long intergenic non-coding RNAS (lincRNAs), 480 pseudogenes, and 642 antisense RNAs that were differentially regulated with IFNγ, IFNγ+TX and IFNγ+CQ treatments. Further analysis of these RNA species based on the existing literature data revealed 6 antisense RNAs, 2 pseudogenes, and 5 lincRNAs that have the potential to modulate MIAMI cell’s response to IFNγ treatment. Functional analysis of these genomic species based on current literature linking inflammatory response and ncRNAs indicated their potential for regulation of several key pro- and anti-inflammatory responses, including NFκB signaling, cytokine secretion and auto-immune responses. Overall, this work found potential involvement of multiple pro-and anti-inflammatory pathways and molecules in modulating MIAMI cells’ response to inflammation.