Decreasing lncRNA HOTAIR expression inhibits human colorectal cancer stem cells

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Aberrant long non-coding RNA (lncRNA) expression is increasingly linked to cancer stem cell (CSC) biology.
• The role of lncRNA HOTAIR in colorectal cancer (CRC) stem cells requires further investigation.

Purpose of the Study:

• To investigate the effect of decreasing lncRNA HOTAIR expression on human colorectal cancer stem cells.
• To evaluate HOTAIR's role in the proliferation, migration, invasion, and tumorigenicity of colorectal cancer stem cells.

Main Methods:

• Isolation of CD133(+) CSCs from the human CRC LoVo cell line using magnetic-activated cell sorting.
• Transfection of CD133(+) CSCs with small hairpin RNA targeting HOTAIR (shHOTAIR).
• Assessment of cellular proliferation, migration, invasion, colony formation, epithelial-mesenchymal transition (EMT)-associated molecule expression, and tumorigenicity using MTT, wound-healing, invasion, colony formation, and Western blot assays.

Main Results:

• Down-regulation of HOTAIR in CD133(+) CSCs suppressed cellular proliferation, migration, invasion, and colony formation in vitro.
• Reduced HOTAIR expression led to decreased Vimentin and increased E-cadherin expression, indicating inhibition of EMT.
• In vivo studies showed that down-regulating HOTAIR in CD133(+) CSCs significantly attenuated tumor growth and lung metastasis in xenograft nude mice.

Conclusions:

• Decreasing lncRNA HOTAIR expression in CD133(+) colorectal cancer stem cells inhibits their invasive and metastatic potential.
• Down-regulation of HOTAIR represents a potential anti-cancer therapeutic strategy for inhibiting colorectal cancer stem cell invasiveness and metastasis.