Circular RNA PCDH10 regulates the tumorigenesis of pancreatic cancer through the miR-338-3p/hTERT axis.

Protocadherin-10 (PCDH10) was previously identified as a pancreatic cancer (PC) suppressor by reducing telomerase activity through binding with human telomerase reverse transcriptase (hTERT). However, we did not observe any effects of PCDH10 on hTERT mRNA or protein expression. Our research found that the PCDH10 gene could be transcribed into linear mRNA or circular RNA, and FUS could bind to the introns flanking the circularized exons, inducing the PCDH10 linear mRNA to shift to circPCDH10 in PC cells. Knockdown of circPCDH10 significantly inhibited PC progression. Mechanistically, circPCDH10 acted as a sponge of miR-338-3p, which could negatively regulate hTERT expression in PC cells. The inhibitory effects of circPCDH10 knockdown on PC cells could be notably reversed by miR-338-3p inhibition and ectopic expression of hTERT. Overall, we propose that the increased FUS expression in PC cells made circPCDH10 the preferred product of the PCDH10 gene, and circPCDH10 might promote PC progression through upregulation of hTERT expression by targeting miR-338-3p. AJTR