期刊
AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH
卷 13, 期 4, 页码 2181-2197出版社
E-CENTURY PUBLISHING CORP
关键词
Pancreatic cancer; protocadherin-10; linear; circular; FUS; human telomerase reverse transcriptase
PCDH10 gene can be transcribed into linear mRNA or circular RNA, with FUS protein inducing the linear mRNA to shift to circPCDH10 in pancreatic cancer (PC) cells. CircPCDH10 acts as a sponge of miR-338-3p to regulate hTERT expression, promoting PC progression.
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.
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