Department of Cardiothoracic Surgery, General Hospital of Central Theater Command, Wuhan, Hubei, China.
Department of Cardiothoracic Surgery, Shenzhen University General Hospital, Shenzhen, Guangdong, China.
Cancer Biomark. 2020;29(3):417-427. doi: 10.3233/CBM-200059.
Long non-coding RNA (lncNRA) forkhead box D3 antisense RNA 1 (FOXD3-AS1) has been proved to promote or suppress the occurrence and development of multiple types of human tumors. However, the function and mechanism of FOXD3-AS1 in non-small cell lung cancer (NSCLC) are scarcely understood.
qRT-PCR was used for detecting FOXD3-AS1, miR-150 and SRC kinase signaling inhibitor 1 (SRCIN1) mRNA expression in NSCLC tissues, and the relationship between pathological characteristics of NSCLC patients and FOXD3-AS1 expression level was analyzed. With human NSCLC cell lines H1299 and A549 as cell models, CCK-8 and BrdU assays were employed for detecting cancer cell proliferation, and Transwell assay was employed for detecting cell invasion ability. Dual luciferase reporter gene assay and RNA immunoprecipitation (RIP) assay were used for the verification of the targeting relationshipe between FOXD3-AS1 and miR-150, and Western blot was employed for detecting SRCIN1 protein expression.
FOXD3-AS1 expression was significantly reduced in NSCLC tissues and cell lines, and low expression of FOXD3-AS1 was closely related to positive lymph node metastasis and relatively high tumor grade. FOXD3-AS1 over-expression inhibited the proliferation and invasion of H1299 cell lines, while its knockdown promoted the proliferation and invasion of A549 cells. Additionally, it was confirmed that FOXD3-AS1 suppressed the expression of miR-150 by targeting it, and up-regulated the expression of SRCIN1.
FOXD3-AS1 indirectly enhances the expression of SRCIN1 by targeting miR-150, thereby inhibiting NSCLC progression.
长链非编码 RNA（lncNRA）叉头框 D3 反义 RNA 1（FOXD3-AS1）已被证明可促进或抑制多种类型的人类肿瘤的发生和发展。然而，FOXD3-AS1 在非小细胞肺癌（NSCLC）中的功能和机制仍知之甚少。
qRT-PCR 用于检测 NSCLC 组织中 FOXD3-AS1、miR-150 和 SRC 激酶信号抑制剂 1（SRCIN1）mRNA 的表达，并分析 NSCLC 患者病理特征与 FOXD3-AS1 表达水平的关系。用人非小细胞肺癌细胞系 H1299 和 A549 作为细胞模型，CCK-8 和 BrdU 测定法用于检测癌细胞增殖，Transwell 测定法用于检测细胞侵袭能力。双荧光素酶报告基因测定和 RNA 免疫沉淀（RIP）测定用于验证 FOXD3-AS1 与 miR-150 之间的靶向关系，Western blot 用于检测 SRCIN1 蛋白表达。
FOXD3-AS1 在 NSCLC 组织和细胞系中的表达明显降低，低表达 FOXD3-AS1 与阳性淋巴结转移和相对较高的肿瘤分级密切相关。FOXD3-AS1 的过表达抑制了 H1299 细胞系的增殖和侵袭，而其敲低促进了 A549 细胞的增殖和侵袭。此外，还证实 FOXD3-AS1 通过靶向 miR-150 抑制其表达，并上调 SRCIN1 的表达。
FOXD3-AS1 通过靶向 miR-150 间接增强 SRCIN1 的表达，从而抑制 NSCLC 的进展。
