长链非编码RNA GHET1敲低可在体内外抑制乳腺癌活性。
lncRNA GHET1 knockdown suppresses breast cancer activity in vitro and in vivo.
作者信息
Han Mingli, Wang Yimeng, Gu Yuanting, Ge Xin, Seng Jingjing, Guo Guangcheng, Zhang Xiangyu, Zhao Yang, Dou Dongwei
机构信息
Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University Zhengzhou 450052, China.
The Key Laboratory, The First Affiliated Hospital of Zhengzhou University Zhengzhou 450052, China.
出版信息
Am J Transl Res. 2019 Jan 15;11(1):31-44. eCollection 2019.
Long non-coding RNA gastric carcinoma high-expressed transcript 1 (lncRNA GHET1) is highly expressed in many tumors. The aim of the present study was to determine whether GHET1 inhibition decreases growth and metastasis of MCF-7 breast cancer cells by modulating epidermal growth factor receptor (EGFR) expression. In vitro, lncRNA GHET1 knockdown suppressed cell proliferation, migration, and invasion and enhanced cell apoptosis by maintaining MCF-7 cells in the G1 phase of the cell cycle. Furthermore, lncRNA GHET1 knockdown reduced the expression of EGFR and related proteins. Treatment of mice with a GHET1 inhibitor prevented tumor growth in vivo. The results indicate that lncRNA GHET1 inhibition directly suppresses EGFR expression, significantly inhibiting the downstream PI3K/AKT/Cyclin D1/MMP2/9 pathway. This mechanism may underlie the suppression of breast cancer cell activities including proliferation, migration, and invasion. In conclusion, lncRNA GHET1 knockdown suppresses tumor growth and metastasis by suppressing the activity of EGFR and downstream pathways.
长链非编码RNA胃癌高表达转录本1（lncRNA GHET1）在许多肿瘤中高表达。本研究的目的是确定抑制GHET1是否通过调节表皮生长因子受体（EGFR）的表达来降低MCF-7乳腺癌细胞的生长和转移。在体外，lncRNA GHET1敲低通过使MCF-7细胞维持在细胞周期的G1期来抑制细胞增殖、迁移和侵袭，并增强细胞凋亡。此外，lncRNA GHET1敲低降低了EGFR及相关蛋白的表达。用GHET1抑制剂处理小鼠可在体内抑制肿瘤生长。结果表明，抑制lncRNA GHET1可直接抑制EGFR表达，显著抑制下游PI3K/AKT/细胞周期蛋白D1/MMP2/9通路。这一机制可能是抑制乳腺癌细胞增殖、迁移和侵袭等活动的基础。总之，lncRNA GHET1敲低通过抑制EGFR及其下游通路的活性来抑制肿瘤生长和转移。
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