Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8943848 | Cancer Letters | 2018 | 49 Pages |
Abstract
ChlA-F is a novel conformation-derivative of Cheliensisin A, styryl-lactone isolates that show potent anti-tumor potential in vivo and vitro. However, the anti-cancer activity and its potential mechanisms underlying ChlA-F action have never been explored. In the present study, we evaluated the potency of ChlA-F on autophagy-mediated anchorage-independent growth inhibition in human high-grade invasive bladder cancer (BC) cells. We found that ChlA-F treatment significantly inhibited anchorage-independent growth of human BC cells by inducing autophagy in a Sestrin-2 (SESN2)-dependent fashion. Our results revealed that ChlA-F treatment specifically induced SESN2 expression via increasing its transcription and mRNA stability. On one hand, ChlA-F treatment markedly attenuated Dicer protein abundance, in turn abolishing miR-27a maturation and further relieving miR-27a binding directly to SESN2 mRNA 3â²UTR, thereby promoting SESN2 mRNA stabilization. On the other hand, ChlA-F treatment promoted Sp1 abundance and consequently mediated SESN2 transcription. These results demonstrate that its activation of the autophagic pathway through specifically promoting SESN2 expression mediates the anti-cancer effect of ChlA-F, which offers insights into the novel anti-cancer effect of ChlA-F on BC, as well as providing therapeutic alternatives against human BC.
Keywords
Sestrin2FBSATGIgGGFPSesn240,6-diamidino-2-phenylindoleshRNABAFRFPRT-PCRDAPI3′-UTRshort hairpin RNAactinomycin Dimmunoglobulin Gbafilomycin A1miR-27aAnchorage-independent growthBladder cancerfetal bovine serumAct Dautophagy-related3′-untranslated regionsMicroRNAMiRNAwild typereverse transcription-polymerase chain reactiongreen fluorescent proteinred fluorescent proteinmicrotubule-associated protein 1 light chain 3 betaChloroquine
Related Topics
Life Sciences
Biochemistry, Genetics and Molecular Biology
Cancer Research
Authors
Xiaohui Hua, Jiheng Xu, Xu Deng, Jiawei Xu, Jingxia Li, David Q. Zhu, Junlan Zhu, Honglei Jin, Zhongxian Tian, Haishan Huang, Qin-shi Zhao, Chuanshu Huang,