长链非编码 RNA HOTAIR 通过 miR-217/DACH1 信号通路调控非小细胞肺癌的发生发展。
Long non-coding RNA HOTAIR regulates the development of non-small cell lung cancer through miR-217/DACH1 signaling pathway.
机构信息
Department of Surgery, Chuxiong Medical College, Chuxiong, China.
出版信息
Eur Rev Med Pharmacol Sci. 2019 Jan;23(2):670-678. doi: 10.26355/eurrev_201901_16905.
OBJECTIVE
Long non-coding RNA HOX transcript antisense RNA (HOTAIR) is reported to make chromatin state, cell growth and cancer metastasis. However, the role of HOTAIR in non-small cell lung cancer (NSCLC) remains unknown. The aim of this study was to explore the regulatory mechanism of HOTAIR in NSCLC in relation to miR-217/Dachshund homolog 1 (DACH1) signaling pathway.
MATERIALS AND METHODS
The expression levels of HOTAIR and miR-217 were measured by quantitative Polymerase Chain Reaction (qPCR) in NSCLC cell lines and human bronchial epithelial cell line HBE. The direct target of HOTAIR and miR-217 in NSCLC was confirmed by a Luciferase reporter assay. The expression of DACH1 protein was examined by Western blot (WB) assay. Cell migration and invasion were examined with transwell assays, and cell proliferation was measured by Cell Counting Kit-8 (CCK8) assay.
RESULTS
HOTAIR was up-regulated and miR-217 was down-regulated in NSCLC cell lines. Silencing of HOTAIR significantly repressed cell proliferation and inhibited cell migration and invasion in H1299 and A549 cells by facilitating miR-217 expression. Moreover, bioinformatics analysis and Luciferase reporter assay confirmed that DACH1 was a target of miR-217. Furthermore, the overexpression of miR-217 markedly repressed cell proliferation and inhibited cell migration and invasion in H1299 and A549 cells. DACH1 reverses the effects of miR-217 overexpression in NSCLC cells.
CONCLUSIONS
HOTAIR was up-regulated in NSCLC cell and regulates the proliferation, migration, invasion through the miR-217/DACH1 signaling pathway. It provides a novel potential treatment strategy for NSCLC.
目的
长链非编码 RNA HOX 转录反义 RNA（HOTAIR）被报道可调节染色质状态、细胞生长和癌症转移。然而，HOTAIR 在非小细胞肺癌（NSCLC）中的作用尚不清楚。本研究旨在探讨 HOTAIR 在与 miR-217/达克斯犬同源物 1（DACH1）信号通路相关的 NSCLC 中的调节机制。
材料和方法
通过定量聚合酶链反应（qPCR）测量 NSCLC 细胞系和人支气管上皮细胞系 HBE 中 HOTAIR 和 miR-217 的表达水平。通过荧光素酶报告基因测定证实 HOTAIR 和 miR-217 在 NSCLC 中的直接靶标。通过 Western blot（WB）测定检测 DACH1 蛋白的表达。通过 Transwell 测定检查细胞迁移和侵袭，通过 Cell Counting Kit-8（CCK8）测定测量细胞增殖。
结果
HOTAIR 在 NSCLC 细胞系中上调，miR-217 下调。沉默 HOTAIR 通过促进 miR-217 的表达，显著抑制 H1299 和 A549 细胞的增殖，并抑制细胞迁移和侵袭。此外，生物信息学分析和荧光素酶报告基因测定证实 DACH1 是 miR-217 的靶标。此外，miR-217 的过表达显着抑制 H1299 和 A549 细胞的增殖，并抑制细胞迁移和侵袭。DACH1 逆转了 miR-217 过表达对 NSCLC 细胞的影响。
结论
HOTAIR 在 NSCLC 细胞中上调，并通过 miR-217/DACH1 信号通路调节增殖、迁移和侵袭。它为 NSCLC 提供了一种新的潜在治疗策略。
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