TY - JOUR
T1 - A-to-I-edited miRNA-379-5p inhibits cancer cell proliferation through CD97-induced apoptosis
AU - Xu, Xiaoyan
AU - Wang, Yumeng
AU - Mojumdar, Kamalika
AU - Zhou, Zhicheng
AU - Jeong, Kang Jin
AU - Mangala, Lingegowda S.
AU - Yu, Shuangxing
AU - Tsang, Yiu Huen
AU - Rodriguez-Aguayo, Cristian
AU - Lu, Yiling
AU - Lopez-Berestein, Gabriel
AU - Sood, Anil K.
AU - Mills, Gordon B.
AU - Liang, Han
N1 - Funding Information:
This study was supported in part by grants from the NIH (CA175486 and CA209851 to HL, CCSG grant CA016672, UH3 TR000943, R35 CA209904), a University of Texas System STARS award (to HL), the National Natural Scientific Foundation of China (81572777 to XX), a fellowship from the Gulf Coast Consortia on the Computational Cancer Biology Training Program (Cancer Prevention and Research Institute of Texas grant RP170593 to YW), and a Research Professor Award from the American Cancer Society to (AKS). We thank the MD Anderson high-performance computing core facility for computing, and LeeAnn Chastain for editorial assistance.
Publisher Copyright:
Copyright: © 2019, American Society for Clinical Investigation.
PY - 2019/12/2
Y1 - 2019/12/2
N2 - Both miRNAs and A-to-I RNA editing, a widespread nucleotide modification mechanism, have recently emerged as key players in cancer pathophysiology. However, the functional impact of RNA editing of miRNAs in cancer remains largely unexplored. Here, we focused on an ADAR2-catalyzed RNA editing site within the miR-379-5p seed region. This site was under-edited in tumors relative to normal tissues, with a high editing level being correlated with better patient survival times across cancer types. We demonstrated that in contrast to wild-type miRNA, edited miR-379-5p inhibited cell proliferation and promoted apoptosis in diverse tumor contexts in vitro, which was due to the ability of edited but not wild-type miR-379-5p to target CD97. Importantly, through nanoliposomal delivery, edited miR-379-5p mimics significantly inhibited tumor growth and extended survival of mice. Our study indicates a role of RNA editing in diversifying miRNA function during cancer progression and highlights the translational potential of edited miRNAs as a new class of cancer therapeutics.
AB - Both miRNAs and A-to-I RNA editing, a widespread nucleotide modification mechanism, have recently emerged as key players in cancer pathophysiology. However, the functional impact of RNA editing of miRNAs in cancer remains largely unexplored. Here, we focused on an ADAR2-catalyzed RNA editing site within the miR-379-5p seed region. This site was under-edited in tumors relative to normal tissues, with a high editing level being correlated with better patient survival times across cancer types. We demonstrated that in contrast to wild-type miRNA, edited miR-379-5p inhibited cell proliferation and promoted apoptosis in diverse tumor contexts in vitro, which was due to the ability of edited but not wild-type miR-379-5p to target CD97. Importantly, through nanoliposomal delivery, edited miR-379-5p mimics significantly inhibited tumor growth and extended survival of mice. Our study indicates a role of RNA editing in diversifying miRNA function during cancer progression and highlights the translational potential of edited miRNAs as a new class of cancer therapeutics.
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U2 - 10.1172/JCI123396
DO - 10.1172/JCI123396
M3 - Article
C2 - 31682236
AN - SCOPUS:85076017650
SN - 0021-9738
VL - 129
SP - 5343
EP - 5356
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 12
ER -