The long noncoding RNA HOTTIP promotes breast cancer cell migration, invasiveness, and epithelial–mesenchymal transition via the Wnt–β-catenin signaling pathway

Autor: Xiaoming Jin, Ye Han, Fei Xing, Zhen Liu, Xiao-Peng Yu, Sijia Han, Fang Qiu, Guijin He
Rok vydání: 2019
Předmět:
Zdroj: Biochemistry and Cell Biology. 97:655-664
ISSN: 1208-6002
0829-8211
Popis: Long noncoding RNA HOTTIP (HOXA transcript at the distal tip) has recently been reported to have a role in the proliferation of various cancer cells, yet its role in cell migration, invasiveness, and the EMT (epithelial–mesenchymal transition) in breast cancer 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 invasiveness in these two breast cancer cell lines after knock-down of HOTTIP by shHOTTIP. We also demonstrated that the EMT of these two breast cell lines was suppressed after HOTTIP knock-down, as evidenced by increased E-cadherin levels, and decreased levels of N-cadherin, Snail, and Twist. Moreover, HOTTIP silencing also suppressed tumor metastasis in nude mice in vivo. In addition, we found that the expression of β-catenin was significantly decreased in breast cancer cells after knock-down of HOTTIP. In a further rescue experiment using overexpression of β-catenin, the rates of cell migration, invasiveness, and EMT of HOTTIP-silenced breast cancer cells were promoted, disclosing a potential role of the Wnt–β-catenin signaling pathway in this process. Overall, we discovered the positive regulatory function of HOTTIP in the migration, invasiveness, and EMT of breast cancer cells, via regulating the Wnt–β-catenin pathway.
Databáze: OpenAIRE