Int J Biol Sci 2021; 17(2):498-513. doi:10.7150/ijbs.55636

Research Paper

DGCR5 is activated by PAX5 and promotes pancreatic cancer via targeting miR-3163/TOP2A and activating Wnt/β-catenin pathway

Shi-lei Liu1,2*, Chen Cai1,2*, Zi-yi Yang1,2*, Zi-you Wu1, Xiang-song Wu1,2, Xue-feng Wang1,2, Ping Dong1,2✉, Wei Gong1,2✉

1. Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China
2. Shanghai Key Laboratory of Biliary Tract Disease Research, No. 1665 Kongjiang Road, Shanghai 200092, China
*These authors contributed equally to this work.

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Citation:
Liu Sl, Cai C, Yang Zy, Wu Zy, Wu Xs, Wang Xf, Dong P, Gong W. DGCR5 is activated by PAX5 and promotes pancreatic cancer via targeting miR-3163/TOP2A and activating Wnt/β-catenin pathway. Int J Biol Sci 2021; 17(2):498-513. doi:10.7150/ijbs.55636. Available from https://www.ijbs.com/v17p0498.htm

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Abstract

Long noncoding RNA DiGeorge syndrome critical region gene 5 (DGCR5) has been shown to be highly associated with cancer development. However, the biological role and molecular mechanism of DGCR5 in pancreatic cancer (PC) remains largely unknown. This study aimed to explore the role of DGCR5 in PC. It was revealed that DGCR5 was highly expressed in PC tissues compared with adjacent normal tissues and was associated with poor prognosis in PC patients. Furthermore, DGCR5 depletion inhibited the proliferation, migration and invasion by increasing apoptosis and inducing G0/G1 cell cycle arrest in vitro. Moreover, xenograft assay validated that DGCR5 promotes PC tumor growth in vivo. Mechanistically, DGCR5 was found to act as a ceRNA by sponging miR-3163 to regulate DNA topoisomerase 2-alpha (TOP2A) and inhibit Wnt/β-catenin pathway. In addition, it was found that DGCR5 downregulation could enhance the sensitivity of PC cells to gemcitabine, and ChIP assay showed that PAX5 (Paired Box 5) could bind to the promoter region of DGCR5 and increase its transcription. The results of the present study indicated that DGCR5 may be a potential diagnostic biomarker and therapeutic target for PC.

Keywords: DGCR5, PAX5, miR-3163, TOP2A, Wnt/β-catenin pathway, pancreatic cancer