Hsa_circ_0128846 knockdown attenuates the progression of pancreatic cancer by targeting miR-1270/NR3C1 axis

Hsa_circ_0128846 敲低可靶向 miR-1270/NR3C1 轴减缓胰腺癌进展

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作者:Ming Wang #, Ming Li #, Zehan Liu, Cuinan Jiang, Hailong Lv, Qin Yang

Abstract

The considerable role of circular RNAs (circRNAs) make them prospective biomarkers in cancer therapy. Our study aimed to unveil the function of circ_0128846 in pancreatic cancer (PC). The expressions of circ_0128846, miR-1270 and NR3C1 mRNA were measured via RT-qPCR. The expressions of NR3C1 protein and apoptosis-related markers (Bax and Bcl-2) were measured via western blotting. CCK-8, colony-forming, or wound healing assay was respectively utilized to identify cell proliferation, growth and migration. Xenograft model was developed to evaluate tumor growth affected by circ_0128846 in vivo. The putative binding between miR-1270 and circ_0128846 or NR3C1 was testified by dual-luciferase reporter, RIP or pull-down assay. Circ_0128846 showed elevated expression in PC. Circ_0128846 deficiency restrained cancer cell proliferation, colony formation and migratory ability, enhanced cell apoptotic rate, and also impeded tumor development in vivo. Circ_0128846 directly targeted miR-1270 whose expression was declined in PC. The suppressive effects of silencing circ_0128846 on PC cell malignant phenotypes were largely reversed by miR-1270 inhibition. NR3C1 was targeted by miR-1270 and was highly regulated in PC. The repressive effects of NR3C1 knockdown on PC cell malignant phenotypes were partly abolished by miR-1270 inhibition. Circ_0128846 deficiency blocked PC progression via mediating the miR-1270/NR3C1 pathway, which partly illustrated PC pathogenesis.

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