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MiR-345-5p functions as a tumor suppressor in pancreatic cancer by directly targeting CCL8
- Source :
- Biomedicine & Pharmacotherapy, Vol 111, Iss, Pp 891-900 (2019)
- Publication Year :
- 2019
- Publisher :
- Elsevier, 2019.
-
Abstract
- Background Increasing evidence has demonstrated that microRNAs (miRNAs) are key regulators of human diseases and can serve as prognostic markers for several cancers, such as pancreatic ductal adenocarcinoma (PDAC). Previous studies have revealed various functions for miR-345-5p in several cancers. However, the role and potential mechanism of miR-345-5p in PDAC have not been resolved. Methods Quantitative RT-PCR was performed to investigate the expression levels of miR-345-5p in pancreatic cancer tissues and cell lines, and the effect of miR-345-5p on the proliferation and invasiveness of pancreatic cancer was examined in Transwell assays with miR-345-5p overexpression. We used Western blot assay to explore the underlying mechanisms. Immunofluorescence staining was performed to examine changes in the cytoskeleton of PANC-1 cells in response to miR-345-5p. Luciferase assays were used to clarify the target and regulation mechanism of miR-345-5p. Results miR-345-5p expression was downregulated in PDAC cells and tissues. Upregulated miR-345-5p expression inhibited the proliferation and metastasis of PDAC cells. We identified CCL8 as a direct target of miR-345-5p and found CCL8 expression was inversely correlated with miR-345-5p expression in PDAC samples. CCL8 could activate the NF-κB signaling pathway to promote the proliferation and invasiveness of PDAC cells. These results suggested that miR-345-5p inhibited PDAC progression by inactivating NF-κB signaling. Conclusions Here we demonstrated that miR-345-5p was a tumor-suppressive miRNA in pancreatic cancer progression by targeting CCL8. Our results suggest miR-345-5p may be a potential therapeutic biomarker for pancreatic cancer treatment.
- Subjects :
- 0301 basic medicine
Adult
Male
Proliferation
Down-Regulation
RM1-950
Biology
Metastasis
Cell Line
03 medical and health sciences
0302 clinical medicine
Downregulation and upregulation
Invasion
Pancreatic cancer
Cell Line, Tumor
microRNA
medicine
Chemokine CCL8
Humans
Luciferase
Genes, Tumor Suppressor
Neoplasm Invasiveness
Neoplasm Metastasis
Migration
Aged
Cell Proliferation
Pharmacology
CCL8
PDAC
General Medicine
Middle Aged
medicine.disease
Biomarker (cell)
Up-Regulation
Pancreatic Neoplasms
MicroRNAs
030104 developmental biology
miR-345-5p
Cell culture
030220 oncology & carcinogenesis
Cancer research
Female
Therapeutics. Pharmacology
Signal transduction
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 07533322
- Volume :
- 111
- Database :
- OpenAIRE
- Journal :
- Biomedicine & Pharmacotherapy
- Accession number :
- edsair.doi.dedup.....9b00404c461c8b53e31c0ae8d55058d2