title: Tumor Cell-Derived Microvesicles Induced Not Epithelial-Mesenchymal Transition but Apoptosis in Human Proximal Tubular (HK-2) Cells: Implications for Renal Impairment in Multiple Myeloma.
abstract: Renal impairment (RI) is one of the hallmarks of multiple myeloma (MM) and carries a poor prognosis. Microvesicles (MVs) are membrane vesicles and play an important role in disease progression. Here, we investigated the role of MVs derived from MM cells (MM-MVs) in RI of MM. We found that MM-MVs significantly inhibited viability and induced apoptosis, but not epithelial-mesenchymal transition in human kidney-2 (HK-2), a human renal tubular epithelial cell line. The protein levels of cleaved caspase-3, 8, and 9, and E-cadherin, were increased, but vementin levels were decreased in the HK-2 cells treated with MM-MVs. Through a comparative sequencing and analysis of RNA content between the MVs from RPMI8226 MM cells (RPMI8226-MVs) and K562 leukemia cells, RPMI8226-MVs were enriched with more renal-pathogenic miRNAs, in which the selective miRNAs may participate in the up-regulation of the levels of cleaved caspase-3. Furthermore, the levels of CD138+ circulating MVs (cirMVs) in the peripheral blood were positively correlated with the severity of RI in newly-diagnosed MM. Our study supports MM-MVs representing a previously undescribed factor and playing a potential role in the development of RI of MM patients, and sheds light on the potential application of CD138+ cirMV counts in precise diagnosis of RI in MM and exploring MM-MVs as a therapeutic target.
authors.affiliation: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. zhao_aiqi@163.com.
authors.forename: Aiqi
authors.initials: A
authors.lastname: Zhao
authors.affiliation: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. konglinda212@163.com.|Department of Hematology, The First Affiliated Hospital of Nanchang University, Nanchang 330000, China. konglinda212@163.com.
authors.forename: Fancong
authors.initials: F
authors.lastname: Kong
authors.affiliation: Hubei Bioinformatics & Molecular Imaging Key Laboratory, Department of Bioinformatics and Systems Biology, Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China. samliu@hust.edu.cn.
authors.forename: Chun-Jie
authors.initials: CJ
authors.lastname: Liu
authors.affiliation: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. dysrmygx@sina.com.
authors.forename: Guoxin
authors.initials: G
authors.lastname: Yan
authors.affiliation: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. gaof@hust.edu.cn.
authors.forename: Fei
authors.initials: F
authors.lastname: Gao
authors.affiliation: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. gh273397674@163.com.
authors.forename: Hao
authors.initials: H
authors.lastname: Guo
authors.affiliation: Hubei Bioinformatics & Molecular Imaging Key Laboratory, Department of Bioinformatics and Systems Biology, Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China. guoay@hust.edu.cn.
authors.forename: An-Yuan
authors.initials: AY
authors.lastname: Guo
authors.affiliation: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. zhichaochen@hust.edu.cn.
authors.forename: Zhichao
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. qiubaili@hust.edu.cn.
authors.forename: Qiubai
authors.initials: Q
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000235:genetics; D015415:Biomarkers; D015820:Cadherins / Q000378:metabolism; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D002470:Cell Survival; D055252:Cell-Derived Microparticles / Q000378:metabolism / Q000648:ultrastructure; D004847:Epithelial Cells / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000235:genetics; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D009367:Neoplasm Staging; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D034622:RNA Interference; D051437:Renal Insufficiency / Q000209:etiology; D015398:Signal Transduction; D053668:Syndecan-1 / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism
chemical_list: D015415:Biomarkers; D015820:Cadherins; D035683:MicroRNAs; D019253:Proto-Oncogene Proteins c-bcl-2; D053668:Syndecan-1; D014746:Vimentin; D020169:Caspases
keywords: microvesicles; multiple myeloma; renal impairment