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Updated: Jan 21, 2026

In Vitro Selection of Engineered Transcriptional Repressors for Targeted Epigenetic Silencing
Published on: May 5, 2023
LncRNA FOXC2 antisense transcript accelerates non-small-cell lung cancer tumorigenesis via silencing p15
Zhe Sun1, Chaozhu He2, Miao Xiao2
1Department of Oncology, The First Affiliated Hospital of Nanchang University Nanchang 330006, China.
Abstract:
Non-coding RNAs (ncRNAs) have been demonstrated to modulate the oncogenesis of non-small cell lung cancer (NSCLC), especially the long non-coding RNAs (lncRNAs). However, the role of lncRNA FOXC2-AS1 in the NSCLC is still unclear. In this research, we find that lncRNA FOXC2-AS1 is involved to NSCLC oncogenesis. The ectopic high-expression level of FOXC2-AS1 is closely correlated with the limited NSCLC patients' survival. In the functional experiments, the knockdown of FOXC2-AS1 dramatically suppressed the NSCLC cells' (A549, H460) proliferation, accelerated the apoptosis and induced the cycle arrest at G0/G1 phase. Mechanistic experiments revealed that FOXC2-AS1 repressed the p15 expression via recruiting the polycomb repressive complex 2 (PRC2) to the promoter of p15. The interaction within FOXC2-AS1 and p15 was validated using the rescue experiments. In conclusion, the results in this work confirmed that FOXC2-AS1 could aggravate NSCLC oncogenesis through repressing p15 expression via interacting EZH2, which provide new idea for the NSCLC therapeutic strategy.
Insights
Long non-coding RNA FOXC2-AS1 promotes non-small cell lung cancer (NSCLC) by repressing p15 expression. Targeting FOXC2-AS1 offers a potential therapeutic strategy for NSCLC patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Non-coding RNAs (ncRNAs), particularly long non-coding RNAs (lncRNAs), play a role in cancer development.
- The specific function of lncRNA FOXC2-AS1 in non-small cell lung cancer (NSCLC) remains largely unknown.
Purpose of the Study:
- To investigate the role and mechanism of lncRNA FOXC2-AS1 in NSCLC oncogenesis.
- To explore the potential of FOXC2-AS1 as a therapeutic target for NSCLC.
Main Methods:
- Correlation analysis between FOXC2-AS1 expression levels and NSCLC patient survival.
- Functional experiments involving knockdown of FOXC2-AS1 in NSCLC cell lines (A549, H460).
- Mechanistic studies to elucidate the interaction between FOXC2-AS1, p15, and polycomb repressive complex 2 (PRC2).
Main Results:
- High expression of FOXC2-AS1 correlates with poor survival in NSCLC patients.
- Knockdown of FOXC2-AS1 inhibited NSCLC cell proliferation, induced apoptosis, and caused G0/G1 cell cycle arrest.
- FOXC2-AS1 represses p15 expression by recruiting PRC2 to the p15 promoter, a mechanism confirmed by rescue experiments.
Conclusions:
- FOXC2-AS1 promotes NSCLC oncogenesis by epigenetically silencing the tumor suppressor gene p15 through PRC2 recruitment.
- FOXC2-AS1 represents a potential therapeutic target for NSCLC treatment.
Related Concept Videos
lncRNA - Long Non-coding RNAs
lncRNA - Long Non-coding RNAs
Transcription
Transcription is the process of synthesizing RNA from a DNA sequence by RNA polymerase. It is the first step in producing a protein from a gene sequence. Additionally, many other proteins and regulatory sequences are involved in the proper synthesis of messenger RNA (mRNA). Regulation of transcription is responsible for the differentiation of all the different types of cells and often for the proper cellular response to environmental signals.
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