Differentially Expressed microRNAs in MIA PaCa-2 and PANC-1 Pancreas Ductal Adenocarcinoma Cell Lines are Involved in Cancer Stem Cell Regulation

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.

<p>Blocking circ_0013912 Suppressed Cell Growth, Migration and Invasion of Pancreatic Ductal Adenocarcinoma Cells in vitro and in vivo Partially Through Sponging miR-7-5p</p>

“…28 Furthermore, miR-7-5p was involved in cancer stem cells suppression and drug resistance. 29,30 Here, we supported the downregulation of miR-7-5p in PDAC tissues and cell lines, 18,26,27 and this low expression could contribute to cell proliferation, colony formation, cell cycle entrance, migration and invasion of PANC-1 and AsPC-1 cells with circ_0013912 knockdown or not. The proliferation and invasion of AsPC-1 and BxPC-3 cells were restrained by miR-7-5p overexpression, 31 as well.…”

“…The interaction network analysis had constructed a miR-7-5p gene network through targeting RAF1, PIK3, IGF1R, AKT3, etc. 29 Whereas the downstream functional genes of circ_0013912-miR-7-5p axis were left to be further explored, as well as other vital cell behaviors, such as epithelial-mesenchymal transition and autophagy. 26,28 Additionally, the relevant signaling pathways should also be detected, such as JAK/STAT3, AMPK-mTOR, MAPK and NF-kB pathways.…”

Functional expression of the transient receptor potential ankyrin type 1 channel in pancreatic adenocarcinoma cells

“…However, the expression level is different in PDAC cell lines, which indicate that the channel expression depends on intrinsic features of each cell line. For instance, MIA Paca-2 and Panc-1 relevant as in vitro models for PDAC, are both poorly differentiated cell lines 19 but differ in tumorigenity, miRNA profile 20 , or expression of stem cell markers 21 . Likely others, yet unknown features also influence the expression of membrane proteins and particularly, of TRPA1.…”

Preclinical models of pancreatic ductal adenocarcinoma: challenges and opportunities in the era of precision medicine

“…For instance, a comparison of the expression profile between chemosensitive and chemoresistant PDAC cell lines [92] revealed differential expression of epithelial-to-mesenchymal transition (EMT)related genes, a finding that was confirmed by real-time PCR. Similar methods were exploited to elucidate key mRNAs involved in cancer stem cell regulation [93]. Currently, more target searching strategies are being developed to excavate these genetic resources.…”