Knockdown of HMGA1 inhibits human breast cancer cell growth and metastasis in immunodeficient mice

• Overexpression of HMGA1 has been previously implicated in breast carcinogenesis.
• An RNAi-based HMGA1-silencing construct with co-expression of EmGFP was generated.
• HMGA1-silenced MDA-MB-231 human breast cancer cells were generated.
• Knockdown of HMGA1 impairs anchorage-independent growth and tumorsphere formation.
• Knockdown of HMGA1 impairs xenograft growth and metastasis in immunodeficient mice.

The high mobility group A1 gene (HMGA1) has been previously implicated in breast carcinogenesis, and is considered an attractive target for therapeutic intervention because its expression is virtually absent in normal adult tissue. Other studies have shown that knockdown of HMGA1 reduces the tumorigenic potential of breast cancer cells in vitro. Therefore, we sought to determine if silencing HMGA1 can affect breast cancer development and metastatic progression in vivo. We silenced HMGA1 expression in the human breast cancer cell line MDA-MB-231 using an RNA interference vector, and observed a significant reduction in anchorage-independent growth and tumorsphere formation, which respectively indicate loss of tumorigenesis and self-renewal ability. Moreover, silencing HMGA1 significantly impaired xenograft growth in immunodeficient mice, and while control cells metastasized extensively to the lungs and lymph nodes, HMGA1-silenced cells generated only a few small metastases. Thus, our results show that interfering with HMGA1 expression reduces the tumorigenic and metastatic potential of breast cancer cells in vivo, and lend further support to investigations into targeting HMGA1 as a potential treatment for breast cancer.