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Page 56
allied
academies
Journal of Gastroenterology and Digestive Diseases | Volume 3
May 25-26, 2018 | New York, USA
World Liver Conference 2018
I
ncreasing significance of tumor– stromal interaction in
development and progression of cancer implies that
signaling molecules in the tumor microenvironment (TME)
might be the effective therapeutic targets for hepatocellular
carcinoma (HCC). Here, the role of microRNA miR-199a-3p
in the regulation of TME and development of HCC has been
investigated by several
in vitro
and
in vivo
assays. Expression
of miR-199a-3p was observed significantly low in HCC tissues
and its overexpression remarkably inhibited
in vivo
tumor
growth and metastasis to lung in NOD-SCID mice.
In vitro
restoration of miR-199a-3p expression either in endothelial
cells (ECs) or in cancer cells (CACs) significantly diminished
migration of ECs in co-culture assay. Again incubation
of miR-199a-3p transfected ECs with either conditioned
media (CM) of CACs or recombinant VEGF has reduced tube
formation, in ECs and it was also dropped upon growth in
CM of either anti-VEGF antibody-treated or miR-199a-3p-
transfected CACs. In addition, bioinformatics and luciferase-
reporter assays revealed that miR-199a-3p inhibited VEGF
secretion from CACs and VEGFR1 and VEGFR2 expression
on ECs and thus restricted cross talk between CACs and
ECs. Again, restoration of miR-199a-3p in hepatic stellate
cells (HSCs) reduced migration and invasion of CACs in co-
culture assay, while it was enhanced by the overexpression
of HGF suggesting miR-199a-3p has hindered HSC-CACs
cross talk probably by inhibiting HGF and regulating matrix
metalloproteinase MMP2, which were found as targets
of miR-199a-3p subsequently by luciferase-reporter assay
and gelatin zymography, respectively. Thus, these findings
collectively highlight that miR-199a-3p restricts metastasis,
invasion and angiogenesis in HCC and hence it may be
considered as one of the powerful effective therapeutics for
management of HCC patients.
MiRNA199a-3p controls liver Tumor Microenvironment (TME)
Soma Banerjee
Center for Livcr Research, India