Department of Breast Surgery, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China.
Department of Endocrinology, Northern Theater Command Airforce Hospital of Chinese PLA, Shenyang 110042, People's Republic of China.
Biochem Cell Biol. 2019 Oct;97(5):655-664. doi: 10.1139/bcb-2018-0313. Epub 2019 Jan 24.
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.
长链非编码 RNA HOTTIP（HOXA 转录物在远端尖端）最近被报道在各种癌细胞的增殖中具有作用，但它在乳腺癌中的细胞迁移、侵袭和 EMT（上皮-间充质转化）中的作用以及潜在的机制仍不清楚。我们用针对 HOTTIP 的 shRNA（短发夹 RNA）转染乳腺癌细胞系 MDA-MB-231 和 MDA-MB-468。在敲低 HOTTIP 后，我们观察到这两种乳腺癌细胞系的迁移和侵袭能力显著下降。我们还证明，HOTTIP 敲低后，这两种乳腺癌细胞系的 EMT 受到抑制，表现为 E-钙黏蛋白水平升高，N-钙黏蛋白、Snail 和 Twist 水平降低。此外，HOTTIP 沉默也抑制了体内裸鼠的肿瘤转移。此外，我们发现敲低 HOTTIP 后乳腺癌细胞中 β-连环蛋白的表达显著降低。在用过表达 β-连环蛋白进行进一步的挽救实验中，HOTTIP 沉默的乳腺癌细胞的迁移、侵袭和 EMT 率得到了促进，揭示了 Wnt-β-连环蛋白信号通路在此过程中的潜在作用。总的来说，我们发现 HOTTIP 通过调节 Wnt-β-连环蛋白通路在乳腺癌细胞的迁移、侵袭和 EMT 中具有正向调节功能。
