The long non-coding RNA HOTTIP promotes breast cancer cell migration, invasion, and epithelial-mesenchymal transition via Wnt/β-catenin pathway

Long non-coding RNA HOTTIP (HOXA transcript at the distal tip) has been reported to participate in proliferation of various cancer cells recently, yet its role in migration/invasion and EMT (epithelial-mesenchymal transition) of breast cancer cells and the potential mechanisms remain unknown. Breast cancer cell lines MDA-MB-231 and MDA-MB-468 were transfected with shRNA (short hairpin RNA) that specifically targeting HOTTIP. We observed a remarkable decrease in migration and invasion in two breast cancer cell lines after HOTTIP knockdown by sh-HOTTIP. We also demonstrated that EMT of these two breast cell lines was suppressed after HOTTIP knockdown as evidenced by increased E-cadherin level, and decreased N-cadherin, Snail, and twist levels. Moreover, HOTTIP silencing also suppressed tumor metastasis in nude mice in vivo. In addition, we found that the expression of β-catenin was remarkably decreased in breast cancer cells after knockdown of HOTTIP. In a further rescue experiment by overexpression of β-ca...