Dihydroartemisinin suppresses pancreatic cancer cells via a microRNA-mRNA regulatory network
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Yilong Li1, Yongwei Wang1, Rui Kong1, Dongbo Xue2, Shangha Pan1, Hua Chen1, Bei Sun1
1Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China
2Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China
Bei Sun, email: [email protected]
Hua Chen, email: [email protected]
Keywords: dihydroartemisinin, pancreatic cancer, microRNA, microRNA-mRNA regulatory network
Received: December 08, 2015 Accepted: August 08, 2016 Published: August 23, 2016
Despite improvements in surgical procedures and chemotherapy, pancreatic cancer remains one of the most aggressive and fatal human malignancies, with a low 5-year survival rate of only 8%. Therefore, novel strategies for prevention and treatment are urgently needed. Here, we investigated the mechanisms underlying the anti-pancreatic cancer effects dihydroartemisinin (DHA). Microarray and systematic analysis showed that DHA suppressed proliferation, inhibited angiogenesis and promoted apoptosis in two different human pancreatic cancer cell lines, and that 5 DHA-regulated microRNAs and 11 of their target mRNAs were involved in these effects via 19 microRNA-mRNA interactions. Four of these microRNAs, 9 of the mRNAs and 17 of the interactions were experimentally verified. Furthermore, we found that the anti-pancreatic caner effects of DHA in vivo involved 4 microRNAs, 9 mRNAs and 17 microRNA-mRNA interactions. These results improve the understanding of the mechanisms by which DHA suppresses proliferation and angiogenesis and promotes apoptosis in pancreatic cancer cells and indicate that DHA, an effective antimalarial drug, might improve pancreatic cancer treatments.
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