Circ_0005273 induces the aggravation of pancreatic cancer by targeting KLF12

Y.-S. Hou, X. Li

Department of GI Medicine, the Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China. lixudoc666@163.com

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• Oncology

OBJECTIVE: The purpose of this study was to explore the potential influences of circ_0005273 and its downstream target KLF12 on the progression of pancreatic cancer.

PATIENTS AND METHODS: Relative levels of circ_0005273 and KLF12 in paired pancreatic cancer tissues and normal tissues were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Then, the differences in clinical indicators and prognosis (overall survival and progression-free survival) between pancreatic cancer patients expressing high and low levels of circ_0005273 were compared. After knockdown of circ_0005273 in AsPC-1 and CFPAC-1 cells, viability and migratory ability were assessed by cell counting kit-8 (CCK-8), transwell and wound healing assays. The regulatory effect of circ_0005273 on KLF12 was determined through Western blotting assay. Finally, the interaction between circ_0005273 and KLF12 was tested by dual-luciferase reporter assay.

RESULTS: It was found that circ_0005273 was upregulated in pancreatic cancer tissues than that in normal tissues. Besides, pancreatic cancer patients expressing a high level of circ_0005273 had higher incidence rates of lymphatic metastasis and distant metastasis, as well as poor prognosis. Knockdown of circ_0005273 weakened the proliferative and migratory abilities of AsPC-1 and CFPAC-1 cells. KLF12 was the target gene binding to circ_0005273, showing a negative expression correlation between each other. Moreover, the protein level of KLF12 was downregulated by knockdown of circ_0005273. KLF12 was able to abolish the regulatory effects of circ_0005273 on the phenotypes of pancreatic cancer cells.

CONCLUSIONS: Circ_0005273 drives proliferative and migratory abilities of pancreatic cancer cells via activating the KLF12, and it is able to predict lymphatic metastasis, distant metastasis and prognosis in pancreatic cancer patients.

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