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LncRNA H19/miR‐194/PFTK1 axis modulates the cell proliferation and migration of pancreatic cancer
Author(s) -
Sun Yunpeng,
Zhu Qiandong,
Yang Wenjun,
Shan Yunfeng,
Yu Zhengping,
Zhang Qiyu,
Wu Huanhuan
Publication year - 2019
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.27669
Subject(s) - wnt signaling pathway , gene knockdown , cancer research , cell growth , microrna , downregulation and upregulation , biology , cell migration , cyclin d1 , signal transduction , long non coding rna , microbiology and biotechnology , cell , cell cycle , cell culture , gene , genetics
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.