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Title: miR-186 inhibits cell proliferation in multiple myeloma by repressing Jagged1

Abstract

MicroRNAs (miRNAs) are small, noncoding ribonucleic acids that regulate gene expression by targeting mRNAs for translational repression and degradation. Accumulating experimental evidence supports a causal role of miRNAs in hematology tumorigenesis. However, the specific functions of miRNAs in the pathogenesis of multiple myeloma (MM) remain to be established. In this study, we demonstrated that miR-186 is commonly downregulated in MM cell lines and patient MM cells. Ectopic expression of miR-186 significantly inhibited cell growth, both in vitro and in vivo, and induced cell cycle G{sub 0}/G{sub 1} arrest. Furthermore, miR-186 induced downregulation of Jagged1 protein expression by directly targeting its 3′-untranslated region (3′-UTR). Conversely, overexpression of Jagged1 rescued cells from miR-186-induced growth inhibition. Our collective results clearly indicate that miR-186 functions as a tumor suppressor in MM, supporting its potential as a therapeutic target for the disease. - Highlights: • miR-186 expression is decreased in MM. • miR-186 inhibits MM cell proliferation in vitro and in vivo. • Jagged1 is regulated by miR-186. • Overexpression of Jagged1 reverses the effects of miR-186.

Authors:
 [1];  [2]; ;  [3];  [1]
  1. Department of Hematology, Qilu Hospital, Shandong University, 107 Wenhuaxi Road, Jinan, Shandong 250012 (China)
  2. Department of Thyroid and Breast Surgery, Hospital Affiliated to Binzhou Medical University, 661 Second Huanghe Street, Binzhou 256603 (China)
  3. Department of Hematology, Hospital Affiliated to Binzhou Medical University, 661 Second Huanghe Street, Binzhou 256603 (China)
Publication Date:
OSTI Identifier:
22594184
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 469; Journal Issue: 3; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CELL CYCLE; CELL PROLIFERATION; GENES; HEMATOLOGY; IN VITRO; IN VIVO; INHIBITION; MESSENGER-RNA; NEOPLASMS; PATHOGENESIS; PATIENTS; PROTEINS

Citation Formats

Liu, Zengyan, Department of Hematology, Hospital Affiliated to Binzhou Medical University, 661 Second Huanghe Street, Binzhou 256603, Zhang, Guoqiang, Yu, Wenzheng, Gao, Na, and Peng, Jun. miR-186 inhibits cell proliferation in multiple myeloma by repressing Jagged1. United States: N. p., 2016. Web. doi:10.1016/J.BBRC.2015.11.136.
Liu, Zengyan, Department of Hematology, Hospital Affiliated to Binzhou Medical University, 661 Second Huanghe Street, Binzhou 256603, Zhang, Guoqiang, Yu, Wenzheng, Gao, Na, & Peng, Jun. miR-186 inhibits cell proliferation in multiple myeloma by repressing Jagged1. United States. https://doi.org/10.1016/J.BBRC.2015.11.136
Liu, Zengyan, Department of Hematology, Hospital Affiliated to Binzhou Medical University, 661 Second Huanghe Street, Binzhou 256603, Zhang, Guoqiang, Yu, Wenzheng, Gao, Na, and Peng, Jun. 2016. "miR-186 inhibits cell proliferation in multiple myeloma by repressing Jagged1". United States. https://doi.org/10.1016/J.BBRC.2015.11.136.
@article{osti_22594184,
title = {miR-186 inhibits cell proliferation in multiple myeloma by repressing Jagged1},
author = {Liu, Zengyan and Department of Hematology, Hospital Affiliated to Binzhou Medical University, 661 Second Huanghe Street, Binzhou 256603 and Zhang, Guoqiang and Yu, Wenzheng and Gao, Na and Peng, Jun},
abstractNote = {MicroRNAs (miRNAs) are small, noncoding ribonucleic acids that regulate gene expression by targeting mRNAs for translational repression and degradation. Accumulating experimental evidence supports a causal role of miRNAs in hematology tumorigenesis. However, the specific functions of miRNAs in the pathogenesis of multiple myeloma (MM) remain to be established. In this study, we demonstrated that miR-186 is commonly downregulated in MM cell lines and patient MM cells. Ectopic expression of miR-186 significantly inhibited cell growth, both in vitro and in vivo, and induced cell cycle G{sub 0}/G{sub 1} arrest. Furthermore, miR-186 induced downregulation of Jagged1 protein expression by directly targeting its 3′-untranslated region (3′-UTR). Conversely, overexpression of Jagged1 rescued cells from miR-186-induced growth inhibition. Our collective results clearly indicate that miR-186 functions as a tumor suppressor in MM, supporting its potential as a therapeutic target for the disease. - Highlights: • miR-186 expression is decreased in MM. • miR-186 inhibits MM cell proliferation in vitro and in vivo. • Jagged1 is regulated by miR-186. • Overexpression of Jagged1 reverses the effects of miR-186.},
doi = {10.1016/J.BBRC.2015.11.136},
url = {https://www.osti.gov/biblio/22594184}, journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 3,
volume = 469,
place = {United States},
year = {Fri Jan 15 00:00:00 EST 2016},
month = {Fri Jan 15 00:00:00 EST 2016}
}