Aptamer-guided targeting of the intracellular long-noncoding RNA HOTAIR

Area of Science:

• Oncology
• Molecular Biology
• RNA Therapeutics

Background:

• Long non-coding RNAs (lncRNAs) are emerging as critical regulators in cancer, presenting therapeutic targets.
• Targeting lncRNAs like HOTAIR (HOX antisense intergenic RNA) is challenging due to the need for tumor-specific delivery systems.
• Epidermal growth factor receptor (EGFR) is a key driver in triple-negative breast cancer (TNBC) and regulates HOTAIR expression.

Purpose of the Study:

• To develop a targeted delivery system for suppressing HOTAIR in EGFR-expressing cancer cells.
• To evaluate the efficacy of an EGFR aptamer-coupled siRNA against HOTAIR (siHOTAIR) in preclinical cancer models.

Main Methods:

• Constructed a chimeric molecule combining an EGFR-targeting aptamer with siHOTAIR.
• Assessed the preferential down-regulation of HOTAIR in EGFR-expressing cancer cells.
• Investigated the impact of EGFR aptamer-coupled siHOTAIR on cancer cell proliferation, migration, and invasion.

Main Results:

• EGFR aptamer-coupled siHOTAIR effectively and specifically reduced HOTAIR levels in EGFR-positive cancer cells.
• This targeted approach significantly inhibited the growth, migration, and invasion of EGFR-expressing TNBC cells.
• Efficacy was observed in cells with high EGFR expression and those with reconstituted EGFR.

Conclusions:

• Aptamer-directed delivery of anti-lncRNA RNA interference offers a novel strategy for targeting cancer progression.
• This approach demonstrates potential applicability across different cancer types and cellular contexts expressing specific biomarkers like EGFR.