Dihydroartemisinin suppresses pancreatic cancer cells via a microRNA-mRNA regulatory network.
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.
Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
Yilong
Y
Li
Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
Yongwei
Y
Wang
Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
Rui
R
Kong
Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
Dongbo
D
Xue
Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
Shangha
S
Pan
Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
Hua
H
Chen
Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
Bei
B
Sun
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins; D037621:Artemisinins / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D053263:Gene Regulatory Networks; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000378:metabolism*; D009389:Neovascularization, Pathologic; D020411:Oligonucleotide Array Sequence Analysis; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D014162:Transfection
D051017:Apoptosis Regulatory Proteins; D037621:Artemisinins; D035683:MicroRNAs; D012333:RNA, Messenger; C039060:artenimol
dihydroartemisinin; microRNA; microRNA-mRNA regulatory network; pancreatic cancer