LncRNA HOTAIR promotes DNA damage repair and radioresistance by targeting ATR in colorectal cancer
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View abstract on PubMed
Summary
This summary is machine-generated.Long non-coding RNA HOTAIR promotes colorectal cancer radioresistance by interacting with ATR, facilitating DNA damage repair. Silencing HOTAIR enhances radiosensitivity and suppresses tumor growth.
Area Of Science
- Oncology
- Molecular Biology
- Genetics
Background
- Long non-coding RNAs (lncRNAs) are increasingly recognized for their roles in cancer progression and treatment resistance.
- The HOX transcript antisense intergenic RNA (HOTAIR) has been linked to colorectal cancer (CRC) development.
- Understanding the mechanisms of radiotherapy resistance in CRC is crucial for improving patient outcomes.
Purpose Of The Study
- To investigate the functional role of HOTAIR in conferring radiotherapy resistance in colorectal cancer cells.
- To elucidate the underlying molecular mechanism by which HOTAIR influences radiosensitivity.
- To assess the correlation between HOTAIR expression and clinical features in CRC patients.
Main Methods
- Quantitative analysis of HOTAIR expression in CRC tissues and cell lines.
- Functional assays including cell proliferation, colony formation, and apoptosis assays.
- RNA pull-down and fluorescence in situ hybridization (FISH) to determine HOTAIR-ATR interaction.
- In vivo studies using a mouse xenograft model.
Main Results
- HOTAIR was significantly upregulated in CRC tumors, particularly in radioresistant samples, and correlated with poor prognosis.
- Silencing HOTAIR reduced CRC cell proliferation, promoted apoptosis, and increased radiosensitivity.
- HOTAIR interacted with the DNA damage response mediator ATR, regulating the DNA damage repair pathway and cell cycle progression.
- HOTAIR knockdown in a mouse xenograft model inhibited tumor growth and enhanced radiotherapy sensitivity.
Conclusions
- lncRNA HOTAIR plays a critical role in promoting radioresistance in colorectal cancer.
- HOTAIR facilitates the DNA damage response pathway by targeting ATR, thereby enhancing tumor cell survival after radiation.
- Targeting HOTAIR may represent a potential therapeutic strategy to overcome radiotherapy resistance in CRC.
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