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Inducible and Reversible Dominant-negative DN Protein Inhibition
Published on: January 7, 2019
Long non-coding RNA HOTAIR regulates proliferation and invasion via activating Notch signalling pathway in
Changxia Dong1, Shaoyi Liu, Yongbin Lv
1Yantai Yuhuangding Hospital, Qingdao University School of Medicine, Yantai City, Shandong Province, People's Republic of China.
Abstract:
Retinoblastoma is the most frequently occurring tumour in the eyes in early childhood. Novel targets that are important for the diagnosis or treatment of retinoblastoma could be valuable in increasing the survival rate of patients affected by this disease. Long non-coding RNAs (lncRNAs) are a recently discovered type of RNAs with no proteincoding function; yet it has become increasingly clear that lncRNAs are responsible for important gene regulatory functions in various diseases. In this study, the expression of lncRNA HOTAIR was measured by qRT-PCR, and HOTAIR expression was found to be significantly upregulated in human retinoblastomas tissues as compared with that in paracancerous tissues. Knockdown of HOTAIR restricted the proliferation and invasion of the more invasive retinoblastoma Y79 cells, and led to G0/G1 arrest, possibly through inhibiting phospho-RB1, RB1 and CCNE. Furthermore, we found that the Notch signalling pathway was activated abnormally in retinoblastoma cell lines, while knockdown of HOTAIR attenuated the endogenous Notch signalling pathway in vitro and in vivo. In addition, knockdown of HOTAIR could inhibit the tumour progression in a xenograft model of retinoblastoma. In summary, our findings indicate that HOTAIR may play important roles in retinoblastoma progression via Notch pathway. HOTAIR has the potential to enhance the development of novel targeted diagnostic and therapeutic approaches for retinoblastoma.
Insights
Long non-coding RNA HOTAIR is overexpressed in retinoblastoma, a childhood eye cancer. Inhibiting HOTAIR may offer new diagnostic and therapeutic strategies by impacting cell growth and the Notch pathway.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Retinoblastoma is a common childhood eye tumor.
- Long non-coding RNAs (lncRNAs) are emerging as key gene regulators in diseases.
- Identifying novel therapeutic targets is crucial for improving retinoblastoma patient survival.
Purpose of the Study:
- To investigate the role of lncRNA HOTAIR in retinoblastoma progression.
- To explore HOTAIR's potential as a diagnostic and therapeutic target for retinoblastoma.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) to measure HOTAIR expression in retinoblastoma tissues.
- In vitro studies involving HOTAIR knockdown in Y79 retinoblastoma cells.
- In vivo xenograft model to assess HOTAIR's effect on tumor growth.
- Analysis of cell cycle regulation (G0/G1 arrest) and signaling pathways (Notch).
Main Results:
- HOTAIR expression was significantly upregulated in retinoblastoma tissues compared to adjacent normal tissues.
- Knockdown of HOTAIR inhibited retinoblastoma cell proliferation and invasion, inducing G0/G1 cell cycle arrest.
- HOTAIR knockdown attenuated the Notch signaling pathway both in vitro and in vivo.
- Inhibition of HOTAIR suppressed tumor progression in a retinoblastoma xenograft model.
Conclusions:
- HOTAIR plays a significant role in retinoblastoma progression, potentially through the Notch signaling pathway.
- HOTAIR represents a promising candidate for developing novel diagnostic and therapeutic strategies for retinoblastoma.
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