microRNA-29 can regulate expression of the long non-coding RNA gene MEG3 in hepatocellular cancer
Open accessAbstract
The human genome is replete with long non-coding RNAs (lncRNA), many of which are transcribed and likely to have a functional role. Microarray analysis of >23,000 lncRNAs revealed downregulation of 712 (~3%) lncRNA in malignant hepatocytes, among which maternally expressed gene 3 (MEG3) was downregulated by 210-fold relative to expression in non-malignant hepatocytes. MEG3 expression was markedly reduced in four human hepatocellular cancer (HCC) cell lines compared with normal hepatocytes by real-time PCR. RNA in situ hybridization showed intense cytoplasmic expression of MEG3 in non-neoplastic liver with absent or very weak expression in HCC tissues. Enforced expression of MEG3 in HCC cells significantly decreased both anchorage-dependent and -independent cell growth, and induced apoptosis. MEG3 promoter hypermethylation was identified by methylation-specific PCR and MEG3 expression was increased with inhibition of methylation with either 5-Aza-2-Deoxycytidine, or siRNA to DNA Methyltransferase (DNMT) 1 and 3b in HCC cells. MiRNA-dependent regulation of MEG3 expression was studied by evaluating the involvement of miR-29, which can modulate DNMT 1 and 3. Overexpression of mir-29a increased expression of MEG3. GTL2, the murine homolog of MEG3, was reduced in liver tissues from hepatocyte-specific miR-29a/b1 knock-out mice compared with wild-type controls. These data show that methylation-dependent tissue-specific regulation of the lncRNA MEG3 by miR-29a may contribute to HCC growth and highlight the inter-relationship between two classes of non-coding RNA, miRNAs and lncRNAs, and epigenetic regulation of gene expression.
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miR-29 can regulate expression of MEG3, a tumor suppressive lncRNA, and miR-29 expression is down regulated in human HCC cells.
“miR-29 can regulate expression of MEG3, a tumor suppressive lncRNA, and miR-29 expression was down regulated in human HCC cells (14).”
From Analysis of Extracellular RNA by Digital PCR (2014) · cites this paper as [14]
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“miR-29 can regulate expression of MEG3, a tumor suppressive lncRNA, and miR-29 expression was down regulated in human HCC cells (14).”
BackgroundSelf-citation
- Authors
- Braconi, C., Kogure, T., Valeri, N., Huang, N., Nuovo, G., Costinean, S., Negrini, M., Miotto, E., Croce, C. M., & Patel, T.
- Affiliations
- The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (US)
- The Ohio State University (US)
- University of Ferrara (IT)
- Corresponding author
- Patel, T
- Venue
- Oncogene
- Published
- 2011-05-30
- Volume
- 30
- Issue
- 47
- Pages
- 4750-4756
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- PMC
- PMC4292930
- OpenAlex
- W2061427860
- Cited by
- 642
- References
- 2
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 14 · 2023: 20 · 2022: 37 · 2021: 42 · 2020: 67 · 2019: 51 · 2018: 60 · 2017: 77 · 2016: 58 · 2015: 70 · 2014: 55 · 2013: 45 · 2012: 27
- FWCI
- 14.37
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Oncogene (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
- Institutional Research Information System University of Ferrara (University of Ferrara) (submittedVersion, other-oa)
- Funders
- National Cancer Institute (P30CA016058)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK069370)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- miR-29a, MEG3, long non-coding RNA, hepatocellular carcinoma, DNA methylation, epigenetic regulation, DNMT1, DNMT3B, tumor growth, apoptosis, lncRNA-miRNA interaction, hepatocyte-specific knockout mice
- MeSH terms
- Carcinoma, Hepatocellular, Humans, Liver Neoplasms, Organ Specificity, Proteins, Gene Expression Regulation, Neoplastic, DNA Methylation, RNA, Untranslated, MicroRNAs, Epigenesis, Genetic, RNA, Long Noncoding
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