Dihydroartemisinin suppresses pancreatic cancer cells via a microRNA-mRNA regulatory network.
Dihydroartemisinin suppresses pancreatic cancer cells via a microRNA-mRNA regulatory network.
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双氢青蒿素通过 microRNA-mRNA 调控网络抑制胰腺癌细胞
DOI：
10.18632/oncotarget.11517
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发表时间：
2016-09-20
期刊：
影响因子：
--
通讯作者：
Sun B
中科院分区：
文献类型：
--
作者：
Li Y;Wang Y;Kong R;Xue D;Pan S;Chen H;Sun B
尽管外科手术和化疗技术有所进步，但胰腺癌仍然是最具侵袭性和致命性的人类恶性肿瘤之一，其5年生存率只有8%。因此，迫切需要新的预防和治疗策略。在这里，我们研究了双氢青蒿素（DHA）抗胰腺癌作用的机制。芯片和系统分析显示，DHA在两种不同的人胰腺癌细胞系中抑制增殖、抑制血管生成和促进细胞凋亡，并且DHA调控的5种microrna和11种靶mrna通过19种microRNA-mRNA相互作用参与了这些作用。其中4个microrna， 9个mrna和17个相互作用经过实验验证。此外，我们发现DHA在体内的抗胰腺癌作用涉及4个microrna， 9个mrna和17个microRNA-mRNA相互作用。这些结果提高了对DHA抑制胰腺癌细胞增殖、血管生成和促进细胞凋亡机制的认识，并提示DHA作为一种有效的抗疟疾药物，可能改善胰腺癌的治疗。
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.