Department of Oncology, Binzhou City Center Hospital, Binzhou, Shandong, China.
Eur Rev Med Pharmacol Sci. 2018 Sep;22(18):5938-5945. doi: 10.26355/eurrev_201809_15923.
This study was made to investigate whether long noncoding RNA (lncRNA) MEG3 could participate in the occurrence and development of non-small cell lung cancer (NSCLC) by regulating the expression of BRCA1 through competitive binding to microRNA-7-5p.
We used quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) to explore the expression of lncRNA MEG3 and BRCA1 in NSCLC tissues and adjacent normal tissues, as well as NSCLC cell lines. The dual luciferase reporter gene assay was used to detect the binding of microRNA-7-5p to lncRNA MEG3 and BRCA1. Meanwhile, the expression of BRCA1, B-cell lymphoma-2 (Bcl-2) and BCL2-associated X (Bax) was detected by Western blot after the cells were overexpressed or knocked down of lncRNA MEG3. All these experiments were designed to investigate whether lncRNA MEG3 participated in the pathogenesis of NSCLC through inhibiting the expression of BRCA1 and Bcl-2 and promoting Bax expression.
The expressions of lncRNA MEG3 and BRCA1 in NSCLC tissues and A549 and HCC823 cell lines were significantly lower than those in the normal group. Overexpression of lncRNA MEG3 and BRCA1 in A549 and HCC823 cell lines resulted in increased apoptosis of lung cancer cells. Dual luciferase reporter assay demonstrated that lncRNA MEG3 can regulate the expression of BRCA1 through competitively binding to microRNA-7-5p to form the lncRNA MEG3/microRNA-7-5p/BRCA1 regulatory network. Besides, lncRNA MEG3 could inhibit the apoptosis inhibitory protein Bcl-2 and promote the expression of apoptosis-promoting factor Bax.
LncRNA MEG3 was significantly downregulated in NSCLC, and it could regulate the BRCA1 expression by competitive binding to microRNA-7-5p.
本研究旨在探讨长链非编码 RNA（lncRNA）MEG3 是否可以通过与 microRNA-7-5p 竞争结合来调节 BRCA1 的表达，从而参与非小细胞肺癌（NSCLC）的发生和发展。
我们使用实时定量聚合酶链反应（qRT-PCR）来探讨 NSCLC 组织和相邻正常组织以及 NSCLC 细胞系中 lncRNA MEG3 和 BRCA1 的表达。双荧光素酶报告基因检测用于检测 microRNA-7-5p 与 lncRNA MEG3 和 BRCA1 的结合。同时，通过过表达或敲低 lncRNA MEG3 后，通过 Western blot 检测 BRCA1、B 细胞淋巴瘤-2（Bcl-2）和 BCL2 相关 X（Bax）的表达。所有这些实验旨在研究 lncRNA MEG3 是否通过抑制 BRCA1 和 Bcl-2 的表达并促进 Bax 表达而参与 NSCLC 的发病机制。
NSCLC 组织和 A549 和 HCC823 细胞系中 lncRNA MEG3 和 BRCA1 的表达明显低于正常组。在 A549 和 HCC823 细胞系中过表达 lncRNA MEG3 和 BRCA1 导致肺癌细胞凋亡增加。双荧光素酶报告基因检测表明，lncRNA MEG3 可以通过竞争性结合 microRNA-7-5p 来调节 BRCA1 的表达，形成 lncRNA MEG3/microRNA-7-5p/BRCA1 调节网络。此外，lncRNA MEG3 可以抑制凋亡抑制蛋白 Bcl-2 并促进凋亡促进因子 Bax 的表达。
lncRNA MEG3 在 NSCLC 中显著下调，并且可以通过与 microRNA-7-5p 竞争结合来调节 BRCA1 的表达。
