Zhang Shenfeng, Qiu Meiqing, Gao Shan, Tian Tao
Department of Oncology, Zaozhuang Municipal Hospital Zaozhuang 277000, Shandong Province, China.
Am J Transl Res. 2021 Apr 15;13(4):2181-2197. eCollection 2021.
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.
原钙黏蛋白-10（PCDH10）先前被鉴定为一种胰腺癌（PC）抑制因子，它通过与人端粒酶逆转录酶（hTERT）结合来降低端粒酶活性。然而，我们并未观察到PCDH10对hTERT mRNA或蛋白表达有任何影响。我们的研究发现，PCDH10基因可转录为线性mRNA或环状RNA，并且FUS可与环化外显子侧翼的内含子结合，促使PC细胞中的PCDH10线性mRNA转变为circPCDH10。敲低circPCDH10可显著抑制PC进展。机制上，circPCDH10充当miR-338-3p的海绵，而miR-338-3p可负向调节PC细胞中的hTERT表达。miR-338-3p抑制和hTERT的异位表达可显著逆转敲低circPCDH10对PC细胞的抑制作用。总体而言，我们提出PC细胞中FUS表达的增加使circPCDH10成为PCDH10基因的首选产物，并且circPCDH10可能通过靶向miR-338-3p上调hTERT表达来促进PC进展。
