Page 77 - CSIR-IGIB Annual Report 2020-21

Non-coding RNAs and epigenetic mechanisms project aims to re-engineer keratinocytes by
Skeletal muscles of normal and obese diabetic
animals were used to quantify levels of miR-
449a, miR-539 and the lncRNA H19.
Overexpression of miR-449a and miR-539 in
C2C12 muscle cells preliminarily demonstrated
them to be targeting HDAC6 and DNMT-3b,
respectively. H19 inhibition significantly
increased levels of HDACs, suggesting a
regulation of these epigenetic modifiers by
ncRNAs. From a list of previously identified
differentially expressed genes, attempts were
made to study the correlation of the ncRNA-
DNMT/HDAC regulation on the altered genes, if
any. A set of genes belonging to the
AMPK/insulin signaling pathways were found to
be affected; these also possess CpG islands and
histone acetylation marks.
Cell-based therapies
Previous work had demonstrated several
miRNAs and the pre-miRNA processing enzyme-
Dicer, to be significantly down-regulated in the
stalled wound healing during diabetes. This
Publications
LncRNAs in cancer: Regulatory and therapeutic implications. Nandwani A, Rathore S, Datta M. Cancer Lett. 2021
Mar 31;501:162-171.
Annual Report 2020-21
ectopically altering levels of these altered
molecules and study the effects on wound
closure. Towards this, experiments were done
using the HaCaT human keratinocyte cell line
where it was observed that use of miR-497 that
significantly increased cellular miR-497 levels,
promoted a modest increase of wound closure
while the miR-497 inhibitor led to a time
dependent inhibition in wound closure as was
observed in a scratch assay in HaCaT cells. Also,
since Dicer levels are downregulated in a
delayed wound healing during diabetes, in an
attempt to assess the potential of Dicer in
wound closure, a scratch was made in control
and Dicer transfected cells, there was increased
cell migration as well as proliferation, and
significant closure of the wound area in the
Dicer transfected cells compared to the control
cells. These indicate a potential role of these
molecules in wound closure. These are being
investigated in detail together with toxicity
assays and in vivo validation.
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