The chemokine scavenging receptor D6/ACKR2 is a target of miR-146a in thyroid cancer
Francesco Pacifico1, Alessio Lepore2, Stefano Mellone1, Luca Sanguigno2, Giorgia Federico2, Adelaide Greco3,4,5, Arturo Brunetti3,4, Antonio Leonardi2
1 Istituto di Endocrinologia e Oncologia Sperimentale, CNR, Naples, Italy
2 Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Federico II University, Naples, Italy
3 Dipartimento di Scienze Biomediche Avanzate, Federico II University, Naples, Italy
4 CEINGE Biotecnologie Avanzate, scarl, Naples, Italy
5 Istituto di Biostrutture e Bioimmagini, CNR, Naples, Italy
Correspondence:
Antonio Leonardi, email:
Keywords: D6/ACKR2 receptor, chemokines, miR-146a, NF-κB, thyroid cancer
Received: April 16, 2017 Accepted: June 25, 2017 Published: June 30, 2017
Abstract
We have previously shown that miR-146a, a NF-κB-regulated microRNA, is strongly expressed in human specimens and cell lines derived from anaplastic thyroid carcinomas (ATC) where it mediates some of the NF-κB pro-tumorigenic functions. By using a bioinformatic analysis, we identified the chemokine scavenger receptor D6/ACKR2 as a target of miR146a in human ATC. We found that the expression of D6/ACKR2 was up-regulated in miR-146a-null ATC cell lines and that the 3’ UTR of D6/ACKR2 mRNA was able to inhibit its expression in parental, but not in miR-146a-null ATC cells. Since human specimens from primary ATC showed a low expression of D6/ACKR2 compared to normal thyroid tissues, we analyzed the effects of D6/ACKR2 over-expression in ATC cells. Different chemokines added to the conditioned medium of D6/ACKR2 over-expressing ATC cells partially failed to drive in vitro monocyte migration, and tumors derived from the injection of the same cells in nude mice showed a decreased number of infiltrating macrophages.
Taken together, these results indicate that ATC cells down-regulate D6/ACKR2 expression through miR-146a activity to sustain leukocyte trafficking inside tumor microenvironment and shed light on a novel mechanism by which NF-κB indirectly inhibits the expression and the function of anti-tumorigenic gene in thyroid cancer.
