Role of human noncoding RNAs in the control of tumorigenesis
Open accessAbstract
Related studies showed that the protein PSF represses proto-oncogene transcription, and VL30–1 RNA, a mouse noncoding retroelement RNA, binds and releases PSF from a proto-oncogene, activating transcription. Here we show that this mechanism regulates tumorigenesis in human cells, with human RNAs replacing VL30–1 RNA. A library of human RNA fragments was used to isolate, by affinity chromatography, 5 noncoding RNA fragments that bind to human PSF (hPSF), releasing hPSF from a proto-oncogene and activating transcription. Each of the 5 RNA fragments maps to a different human gene. The tumorigenic function of the hPSF-binding RNAs was tested in a human melanoma line and mouse fibroblast line, by determining the effect of the RNAs on formation of colonies in agar and tumors in mice. ( i ) Expressing in human melanoma cells the RNA fragments individually promoted tumorigenicity. ( ii ) Expressing in human melanoma cells a shRNA, which causes degradation of the endogenous RNA from which an RNA fragment was derived, suppressed tumorigenicity. ( iii ) Expressing in mouse NIH/3T3 cells the RNA fragments individually resulted in transformation to tumorigenic cells. ( iv ) A screen of 9 human tumor lines showed that each line expresses high levels of several hPSF-binding RNAs, relative to the levels in human fibroblast cells. We conclude that human hPSF-binding RNAs drive transformation and tumorigenesis by reversing PSF-mediated repression of proto-oncogene transcription and that dysfunctional regulation of human hPSF-binding RNA expression has a central role in the etiology of human cancer.
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One non-coding RNA fragment that can bind PSF belongs to a member of the HERVK11 group mapped as MER11C.
“One of the non-coding RNA fragments that can bind PSF was shown to belong to a member of the HERVK11 group mapped as MER11C 18.”
From Are human endogenous retroviruses pathogenic? An approach to testing the hypothesis (2013) · cites this paper as [18]
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Liu, Y., Long, Y., Li, C., Cao, L., Gan, H., Huang, K., & Jia, Y. (2014) · Japanese Journal of Infectious Diseases · doi:10.7883/yoken.jjid.2014.149 · Cited by 40 · see citing works
Association of Genetic Polymorphisms in the LncRNAs with Gastric Cancer Risk in a Chinese Population
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Self-citationAnalysis of the transcriptome in molecular epidemiology studies
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Association between polymorphisms in long non-coding RNA PRNCR1 in 8q24 and risk of gastric cancer
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Self-citationNovel insight into MALAT-1 in cancer: Therapeutic targets and clinical applications
Ren, D., Li, H., Ren-qiu, L., Sun, J., GUO, P., Han, H.-Y., Yang, Y.-H., & Li, J. (2016) · Oncology Letters · doi:10.3892/ol.2016.4138 · Cited by 38 · see citing works
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Multidimensional crosstalk between RNA-binding proteins and noncoding RNAs in cancer biology.
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Long noncoding RNA expression profile of infantile hemangioma identified by microarray analysis
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Long non-coding RNA CCAL/miR-149/FOXM1 axis promotes metastasis in gastric cancer
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Sattarifard, H., Hashemi, M. M., Hassanzarei, S., Narouie, B., & Bahari, G. (2017) · Molecular and Clinical Oncology · doi:10.3892/mco.2017.1462 · Cited by 30 · see citing works
- Authors
- Li, L., Feng, T., Lian, Y., Zhang, G., Garen, A., & Song, X.
- Affiliations
- Sichuan University (CN)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2009-08-04
- Volume
- 106
- Issue
- 31
- Pages
- 12956-12961
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2722347
- OpenAlex
- W2037471476
- Cited by
- 185
- References
- 13
- Citations by year
- 2025: 3 · 2024: 5 · 2023: 7 · 2022: 5 · 2021: 11 · 2020: 19 · 2019: 16 · 2018: 12 · 2017: 23 · 2016: 12 · 2015: 14 · 2014: 15 · 2013: 17 · 2012: 13
- FWCI
- 2.91
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (30700459, 90919005)
- Ministry of Education of the People's Republic of China
- Scientific Research Foundation for Returned Scholars of Ministry of Education (20071108)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- non-coding RNA, PSF, transcriptional repression, carcinogenesis, RNA fragments, melanoma, cancer transformation, shRNA knockdown, tumor suppressor function
- MeSH terms
- PTB-Associated Splicing Factor, Proto-Oncogene Mas, Animals, Cell Line, Cloning, Molecular, Humans, Neoplasms, Proto-Oncogenes, Transcription, Genetic, RNA-Binding Proteins, RNA, Untranslated, NIH 3T3 Cells, Mice
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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