Extracellular vesicles produced in B cells deliver tumor suppressor miR-335 to breast cancer cells disrupting oncogenic programming in vitro and in vivo.
作者： Gonzalo Almanza , Jeffrey J. Rodvold , Brian Tsui , Kristen Jepsen , Hannah Carter
DOI: 10.1038/S41598-018-35968-2
关键词:
摘要: The successful implementation of miRNA (miR) therapies in humans will ultimately rely on the use vehicles with improved cellular delivery capability. Here we tested a new system that leverages extracellular vesicles (EVs) laden tumor suppressor (miR-335) produced B cells by plasmid DNA induction (iEVs). We demonstrate iEVs-335 efficiently and durably restored endogenous miR-335 pool human triple negative breast cancer cells, downregulated expression target gene SOX4 transcription factor, markedly inhibited growth vivo. Remarkably, mediated transcriptional effects persisted tumors after 60 days post orthotopic implantation. Genome-wide RNASeq analysis treated vitro showed regulation discrete number genes only, without broad transcriptome perturbations. This technology may be ideally suited for aimed to restore miRNAs disrupting oncogenic program established escape from control.
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sci-hub.se 参考文章(38)
David P Bartel, MicroRNAs: Genomics, Biogenesis, Mechanism, and Function Cell. ,vol. 116, pp. 281- 297 ,(2004) , 10.1016/S0092-8674(04)00045-5
Mai Isosaka, Takeshi Niinuma, Masanori Nojima, Masahiro Kai, Eiichiro Yamamoto, Reo Maruyama, Takayuki Nobuoka, Toshirou Nishida, Tatsuo Kanda, Takahiro Taguchi, Tadashi Hasegawa, Takashi Tokino, Koichi Hirata, Hiromu Suzuki, Yasuhisa Shinomura, A Screen for Epigenetically Silenced microRNA Genes in Gastrointestinal Stromal Tumors PLOS ONE. ,vol. 10, pp. e0133754- ,(2015) , 10.1371/JOURNAL.PONE.0133754
Aurora Esquela-Kerscher, Frank J. Slack, Oncomirs — microRNAs with a role in cancer Nature Reviews Cancer. ,vol. 6, pp. 259- 269 ,(2006) , 10.1038/NRC1840
Shanwu Gao, Chabane Tibiche, Jinfeng Zou, Naif Zaman, Mark Trifiro, Maureen O’Connor-McCourt, Edwin Wang, Identification and Construction of Combinatory Cancer Hallmark–Based Gene Signature Sets to Predict Recurrence and Chemotherapy Benefit in Stage II Colorectal Cancer JAMA Oncology. ,vol. 2, pp. 37- 45 ,(2016) , 10.1001/JAMAONCOL.2015.3413
Sohail F. Tavazoie, Claudio Alarcón, Thordur Oskarsson, David Padua, Qiongqing Wang, Paula D. Bos, William L. Gerald, Joan Massagué, Endogenous human microRNAs that suppress breast cancer metastasis Nature. ,vol. 451, pp. 147- 152 ,(2008) , 10.1038/NATURE06487
Peter Langfelder, Steve Horvath, WGCNA: an R package for weighted correlation network analysis. BMC Bioinformatics. ,vol. 9, pp. 559- 559 ,(2008) , 10.1186/1471-2105-9-559
Zuzana Cierna, Michal Mego, Pavol Janega, Marian Karaba, Gabriel Minarik, Juraj Benca, Tatiana Sedlácková, Silvia Cingelova, Paulina Gronesova, Denisa Manasova, Daniel Pindak, Jozef Sufliarsky, Ludovit Danihel, James M Reuben, Jozef Mardiak, Matrix metalloproteinase 1 and circulating tumor cells in early breast cancer BMC Cancer. ,vol. 14, pp. 472- 472 ,(2014) , 10.1186/1471-2407-14-472
Changhe Wang, Tao Jiang, MicroRNA-335 represents an independent prognostic marker in cervical cancer Tumor Biology. ,vol. 36, pp. 5825- 5830 ,(2015) , 10.1007/S13277-015-3252-2
Angelo Restivo, Gerardo Piacentini, Silvia Placidi, Claudia Saffirio, Bruno Marino, Cardiac outflow tract: A review of some embryogenetic aspects of the conotruncal region of the heart Anatomical Record-advances in Integrative Anatomy and Evolutionary Biology. ,vol. 288, pp. 936- 943 ,(2006) , 10.1002/AR.A.20367
Stephin J. Vervoort, Ana Rita Lourenço, Ruben van Boxtel, Paul J. Coffer, SOX4 Mediates TGF-β-Induced Expression of Mesenchymal Markers during Mammary Cell Epithelial to Mesenchymal Transition PLOS ONE. ,vol. 8, ,(2013) , 10.1371/JOURNAL.PONE.0053238