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Background

Aberrant microRNA (miRNA) expression is associated with tumor development. This study aimed to elucidate the role of miR-615-5p in the development of pancreatic ductal adenocarcinoma (PDAC).

Methods

Locked nucleic acid in situ hybridization (LNA-ISH) was performed to compare miR-615-5p expression in patients between PDAC and matched adjacent normal tissues. Effects of miR-615-5p overexpression on cell proliferation, apoptosis, colony formation, migration, and invasion were determined in the pancreatic cancer cell lines PANC-1 and MIA PaCa-2. Effects of miR-615-5p on AKT2 were examined by dual-luciferase reporter assay. Lentivirus expressing miR-615 was used to create stable overexpression cell lines, which were subsequently used in mouse xenograft and metastasis models to assess tumor growth, apoptosis and metastasis.

Results

miR-615-5p expression was significantly lower in PDAC than in adjacent normal tissues. Low levels of miR-615-5p were independently associated with poor prognosis (HR: 2.243, 95% CI: 1.190-4.227, P=0.013). AKT2 protein expression was inversely correlated with miR-615-5p expression (r=-0.3, P=0.003). miR-615-5p directly targeted the 3'-untranslated region of AKT2 mRNA and repressed its expression. miR-615-5p overexpression inhibited pancreatic cancer cell proliferation, migration, and invasion in vitro, and tumor growth and metastasis in vivo. Furthermore, miR-615-5p overexpression also induced pancreatic cancer cell apoptosis both in vitro and in vivo.

Conclusions

These results show that miR-615-5p inhibits pancreatic cancer cell proliferation, migration, and invasion by targeting AKT2. The data implicate miR-615-5p in the prognosis and treatment of PDAC."xsd:string
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http://purl.uniprot.org/citations/25856297http://purl.uniprot.org/core/author"Chen J."xsd:string
http://purl.uniprot.org/citations/25856297http://purl.uniprot.org/core/author"Sun Y."xsd:string
http://purl.uniprot.org/citations/25856297http://purl.uniprot.org/core/author"Wang C."xsd:string
http://purl.uniprot.org/citations/25856297http://purl.uniprot.org/core/author"Yu S."xsd:string
http://purl.uniprot.org/citations/25856297http://purl.uniprot.org/core/author"Zhang T."xsd:string
http://purl.uniprot.org/citations/25856297http://purl.uniprot.org/core/author"Jin X."xsd:string
http://purl.uniprot.org/citations/25856297http://purl.uniprot.org/core/author"Jia C."xsd:string
http://purl.uniprot.org/citations/25856297http://purl.uniprot.org/core/date"2015"xsd:gYear
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http://purl.uniprot.org/citations/25856297http://purl.uniprot.org/core/title"MiRNA-615-5p functions as a tumor suppressor in pancreatic ductal adenocarcinoma by targeting AKT2."xsd:string
http://purl.uniprot.org/citations/25856297http://purl.uniprot.org/core/volume"10"xsd:string
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