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Updated: Dec 27, 2025
Studying RNA Interactors of Protein Kinase RNA-Activated during the Mammalian Cell Cycle
Published on: March 5, 2019
Characterization of novel LncRNA P14AS as a protector of ANRIL through AUF1 binding in human cells
Wanru Ma, Juanli Qiao, Jing Zhou1
1Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Division of Etiology, Peking University Cancer Hospital & Institute, Fu-Cheng-Lu #52, Haidian District, Beijing, 100142, China.
Background:
The CDKN2A/B locus contains crucial tumor suppressors and a lncRNA gene ANRIL. However, the mechanisms that coordinately regulate their expression levels are not clear.
Methods:
Novel RNAs transcribed from the CDKN2A gene were screened by CDKN2A-specific RNA capture deep-sequencing and confirmed by Northern blotting and clone-sequencing. Long non-coding RNA (lncRNA) binding proteins were characterized by RNA pull-down combined with mass spectrometry and RNA immunoprecipitation. LncRNA functions in human cells were studied using a set of biological assays in vitro and in vivo.
Results:
We characterized a novel lncRNA, P14AS with its promoter in the antisense strand of the fragment near CDKN2A exon 1b in human cells. The mature P14AS is a three-exon linear cytoplasmic lncRNA (1043-nt), including an AU-rich element (ARE) in exon 1. P14AS decreases AUF1-ANRIL/P16 RNA interaction and then increases ANRIL/P16 expression by competitively binding to AUF1 P37 and P40 isoforms. Interestingly, P14AS significantly promoted the proliferation of cancer cells and tumor formation in NOD-SCID mice in a P16-independent pattern. Moreover, in human colon cancer tissues, the expression levels of P14AS and ANRIL lncRNAs were significantly upregulated compared with the paired normal tissues.
Conclusion:
A novel lncRNA, P14AS, transcribed from the antisense strand of the CDKN2A/P14 gene, promotes colon cancer development by cis upregulating the expression of oncogenic ANRIL.
Insights
A novel long non-coding RNA (lncRNA), P14AS, promotes colon cancer by increasing oncogenic ANRIL expression. This discovery sheds light on cancer development mechanisms and potential therapeutic targets.
Area of Science:
- Molecular Biology
- Cancer Research
- Epigenetics
Background:
- The CDKN2A/B locus is critical for tumor suppression and includes the ANRIL lncRNA.
- Mechanisms regulating coordinated expression of tumor suppressors and ANRIL are unclear.
Purpose of the Study:
- To characterize novel RNAs transcribed from the CDKN2A gene.
- To elucidate the function of a newly identified lncRNA in cancer development.
Main Methods:
- RNA capture deep-sequencing and Northern blotting to identify novel RNAs.
- RNA pull-down, mass spectrometry, and RNA immunoprecipitation to identify lncRNA-binding proteins.
- In vitro and in vivo assays to study lncRNA function.
Main Results:
- A novel lncRNA, P14AS, was identified, transcribed from the antisense strand near CDKN2A.
- P14AS competitively binds AUF1, increasing ANRIL/P16 expression and promoting cancer cell proliferation and tumor formation.
- P14AS and ANRIL are upregulated in human colon cancer tissues.
Conclusions:
- P14AS promotes colon cancer development by upregulating ANRIL expression.
- P14AS represents a novel oncogenic lncRNA with implications for cancer therapy.
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