Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, and thus better understanding of its molecular pathology is crucial for us to devise more effective treatment of this deadly disease. As cancer cell line remains a convenient starting point for discovery and proof-of-concept studies, here we report the miRNA expression characteristics of two cell lines, MIA PaCa-2 and PANC-1, and discovered three miRNAs (miR-7-5p, let-7d, and miR-135b-5p) that are involved in cancer stem cells (CSCs) suppression. After transfection of each miRNA’s mimic into PANC-1 cells which exhibits higher stemness feature than MIA-PaCa-2 cells, partial reduction of CSC surface markers and inhibition of tumor sphere formation were observed. These results enlighten us to consider miRNAs as potential therapeutic agents for pancreatic cancer patients via specific and effective inhibition of CSCs.
Highlights
Pancreatic ductal adenocarcinoma (PDAC), which constitutes 90% of all pancreatic cancers, is one of the most deadly malignant diseases, with an overall five-year survival rate of 8% for all stages combined and is ranked as the fourth leading cause of cancer-related death in the world [1,2]
A total of 33 differentially expressed miRNAs were identified, including 28 up-regulated and 5 down-regulated miRNAs in the PANC-1 cell line compared to MIA PaCa-2 (Table S1)
We have confirmed 18 (13 up- and 5 down-regulated) differentially expressed miRNAs between MIA PaCa-2 and PANC-1 cell lines, and have discovered these miRNAs are involved in the development of several tumors
Summary
Pancreatic ductal adenocarcinoma (PDAC), which constitutes 90% of all pancreatic cancers, is one of the most deadly malignant diseases, with an overall five-year survival rate of 8% for all stages combined and is ranked as the fourth leading cause of cancer-related death in the world [1,2]. Individual differences of patients increase the complexity of PDAC treatments. There is an urgent need to better understand the molecular pathology of PDAC. Four well-known cancer genes (KRAS, TP53, SMAD4 and CDKN2A) act as oncogenes in PDAC [4]. None has been proved effective anti-cancer drug target after decades of research. An alternative is to seek anticancer molecules acting on other components of the genome, such as epigenetic factors [5]. MicroRNAs (miRNAs) are attracting remarkable research attention because of their association with tumor growth, invasion, angiogenesis, and immune evasion. MiRNAs are small (19–24 nucleotides) noncoding RNA molecules that primarily function to repress target mRNA translation. At least 50% of all miRNAs are aberrantly expressed in tumors and exhibit oncogenic or tumor suppressive activities [6]
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