VDR signaling inhibits cancer-associated-fibroblasts’ release of exosomal miR-10a-5p and limits their supportive effects on pancreatic cancer cells

Correspondence to Dr Zhaoshen Li, Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China; zhaoshenli5610@hotmail.com and Dr Xiangyu Kong, Department of Gastroenterology, Changhai Hospital, the Second Military Medical University, 168 Changhai Road, Shanghai 200433, China; xiangyukong185@hotmail.com We read with great interest the recent publication by Ferrer-Mayorga et al,1 concerning Vitamin D receptor (VDR) signalling’s impacts on cancer-associated fibroblasts (CAFs) in colorectal cancer (CRC). Twenty (~4%) miRNAs were strongly expressed (>10 000 Transcript per million) and accounted for ~81.2% of all miRNA reads (online supplementary table S1). Since a minimum threshold amount must be reached for miRNAs to repress target mRNAs,4 we focused on the five most abundant miRNAs (miR-10a-5p, 92a-3p, 181a-5p, 191–5 p, 92b-3p, accounts for ~51.51% miRNAs of the miRNome in CAF-derived exosomes) for further studies (table 1). Exosomes from CAFs were extracted before and after 1, 25(OH)2D3 treatment and alterations of the five most abundant exosomal miRNAs were evaluated using RT-PCR. miR-10a-5p, which has the highest ratio in exosomal miRNome, was most significantly decreased compared with the other four miRNAs (figure 1C). [...]we hypothesised that miR-10a-5p could be loaded into exosomes and transmitted to PC cells, which could be inhibited by VDR activation in CAFs.