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Abstract
<p class="first" id="d4970044e107">Pancreatic ductal adenocarcinoma (PDAC) remains
a huge challenge due to its high mortality
and morbidity; gene therapy might be a promising treatment for PDAC. The critical
role of Wnt-signaling pathway in cancer pathogenesis has been widely recognized; cyclin-dependent
kinase 14 (CDK14, PFTK1)-induced low-density lipoprotein receptor-related proteins
5/6 (LRP5/6) phosphorylation is an important issue in Wnt-signaling activation. Long
noncoding RNA (LncRNA)-microRNA (miRNA)-messenger RNA (mRNA) modulating the pathogenesis
of cancers has been regarded as a major mechanism. In the current study, upregulated
lncRNAs positively correlated with PFTK1 were analyzed and selected using The Cancer
Genome Atlas (TCGA) database. Of them, lncRNA H19 can activate Wnt signaling in cancers.
In PDAC tissues, the expression of H19 and PFTK1 were upregulated; H19 knockdown suppressed
the cell proliferation and migration of PDAC, while PFTK1 overexpression partially
attenuated the suppressive effect of H19 knockdown. As analyzed by TCGA and predicted
by online tools, miR-194 was negatively correlated with PFTK1 and might bind to both
H19 and PFTK1, which was further confirmed by luciferase reporter and RNA immunoprecipitation
assays. Moreover, the effect of H19 knockdown on PFTK1 protein and the cell proliferation
and migration could be partially reversed by miR-194 inhibition; H19/miR-194 axis
modulated PDAC cell proliferation and migration through PFTK1 downstream Wnt signaling.
Results suggested that rescuing miR-194 expression in PDAC can inhibit lncRNA H19
and PFTK1 expression, subsequently suppressing PDAC cell proliferation and migration.
Due to the complexity of the lncRNA-miRNA-mRNA network, further in vivo experiments
examining potential side effects are needed in future study to explore the clinical
application of these findings.
</p>