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bioRxiv · 10.1101/2020.09.29.319236

mir-218 modulates ARF6 expression and inhibits pancreatic ductal adenocarcinoma invasion

Rheinheimer, B.·Heimark, R. L.
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Abstract

BackgroundPancreatic ductal adenocarcinoma is an extremely malignant disease with the majority of patients having metastatic disease upon diagnosis. Recently, it was shown the SLIT2 plays a regulatory role in melanoma invasion through the control of invadopodia. Therefore, we sought to determine the mechanism behind miR-218 inhibition of pancreatic cancer invasion. Methodsmir-218 target genes were discovered using three miRNA target prediction websites. Modulation of mir-218 target ARF6 was determined by transfection with antagomirs and mimics to mir-218. Pancreatic cancer migration and invasion were measured using Boyden chamber assays. Invasion was further measured using matrix degradation assays. ResultsWe found that mir-218 modulates ARF6 RNA and protein expression in pancreatic cancer. mir-218 did not inhibit pancreatic cancer cell migration, but did inhibit invasion. mir-218 did not affect the formation of invadopodia in pancreatic cancer cells, but did inhibit the total area of matrix degradation caused by functional invadopodia. ConclusionsThis work suggests that miR-218 is a suppressor of pancreatic ductal adenocarcinoma invasion through a pathway that regulates invadopodia maturation.

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Rheinheimer, B., Heimark, R. L.. 2020-10-01. mir-218 modulates ARF6 expression and inhibits pancreatic ductal adenocarcinoma invasion. https://doi.org/10.1101/2020.09.29.319236

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