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Cited by 82MicroRNA in disease regulationCancer-related molecular mechanisms researchPlant Molecular Biology Research

Nuclear miR-122 directly regulates the biogenesis of cell survival oncomiR miR-21 at the posttranscriptional level

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Wang, Dong, Sun, Xinlei, Wei, Yao, Liang, Hongwei, Yuan, Min, Jin, Fangfang, Chen, Xi, Liu, Yuan +3 more·2018·Nucleic Acids Research
DOI 10.1093/nar/gkx1254PMC PMC5829740
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Abstract

Hepatic miR-122 can serve as a pro-apoptotic factor to suppress tumorigenesis. The underlying mechanism, however, remains incompletely understood. Here we present the first evidence that miR-122 promotes hepatocellular carcinoma cell apoptosis through directly silencing the biogenesis of cell survival oncomiR miR-21 at posttranscriptional level. We find that miR-122 is strongly expressed in primary liver cell nucleus but its nuclear localization is markedly decreased in transformed cells particularly in chemoresistant tumor cells. MiRNA profiling and RT-qPCR confirm an inverse correlation between miR-122 and miR-21 in hepatocellular carcinoma tissues/cells, and increasing or decreasing nuclear level of miR-122 respectively reduces or increases miR-21 expression. Mechanistically, nuclear miR-122 suppresses miR-21 maturation via binding to a 19-nt UG-containing recognition element in the basal region of pri-miR-21 and preventing the Drosha-DGCR8 microprocessor's conversion of pri-miR-21 into pre-miR-21. Furthermore, both in vitro and in vivo studies demonstrate that nuclear miR-122 participates in the regulation of HCC cell apoptosis through modulating the miR-21-targeted programmed cell death 4 (PDCD4) signal pathway.

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Authors
Wang, D., Sun, X., Wei, Y., Liang, H., Yuan, M., Jin, F., Chen, X., Liu, Y., Zhang, C.-Y., Li, L., & Zen, K.
Affiliations
  • China Pharmaceutical University (CN)
  • State Key Laboratory of Pharmaceutical Biotechnology (CN)
  • State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, Nanjing Advanced Institute for Life Sciences, School of Life Sciences, Nanjing University, Nanjing, Jiangsu 210093, China
  • Georgia State University (US)
Corresponding author
  • Zhang, Chen-Yu
  • Li, Limin
  • Zen, Ke
ORCID
Venue
Nucleic Acids Research
Publisher
Oxford University Press (OUP)
Published
2017-12-14
Volume
46
Issue
4
Pages
2012-2029
ISSN
  • 0305-1048 (ISSN-L)
  • 1362-4962
DOI
10.1093/nar/gkx1254
PMC
PMC5829740
OpenAlex
W2772545773
Cited by
82
References
1
Citations by year
2026: 4 · 2025: 11 · 2024: 14 · 2023: 9 · 2022: 12 · 2021: 13 · 2020: 7 · 2019: 6 · 2018: 6
FWCI
1.75
Type
journal article
Language
en
Open access
Licence
Locations
  • Nucleic Acids Research (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Funders
  • Georgia State University
  • National Natural Science Foundation of China (91640103, 31770981, 31670917)
  • Government of Jiangsu Province
  • Natural Science Foundation of Jiangsu Province (BK20170076)
  • Six Talent Peaks Project in Jiangsu Province
  • Fundamental Research Funds for the Central Universities (020814380039, 020814380082)
  • National Institute of Allergy and Infectious Diseases (R01AI106839)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Molecular Biology Research
Keywords
miR-122, miR-21, hepatocellular carcinoma, post-transcriptional regulation, apoptosis, PDCD4, chemoresistance
MeSH terms
Animals, Cell Line, Cell Nucleus, Cells, Cultured, Carcinoma, Hepatocellular, Humans, Liver, Liver Neoplasms, Male, Mice, Inbred C57BL, RNA Precursors, RNA Processing, Post-Transcriptional, Gene Expression Regulation, Neoplastic, Mice, SCID, RNA-Binding Proteins, Apoptosis, Drug Resistance, Neoplasm, MicroRNAs, Cell Line, Tumor, Apoptosis Regulatory Proteins

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