Wang Chunyang, Wu Dongmei, He Maofang, Guan Li, Bai Dan, Liang Baihui
Research Center for Prevention and Treatment of Respiratory Disease, College of Clinical Medicine, Xi'an Medical University, Xi'an, China.
Department of Radiation Oncology, Nanxishan Hospital of Guangxi Zhuang Autonomous Region, Guilin, China -
Minerva Med. 2022 Oct;113(5):817-824. doi: 10.23736/S0026-4806.21.07194-9. Epub 2021 Mar 25.
To explore the potential involvement of long non-coding RNA (lncRNA) NORAD in regulating the progression of Non-small cell lung cancer (NSCLC), and its possible mechanism.
Relative level of NORAD in NSCLC tissues and cell lines was determined. Its level in NSCLC patients with different tumor staging (T1-T2, T3-T4) and either with lymphatic metastasis or not was examined as well. Kaplan-Meier curves were depicted for assessing the prognostic value of NORAD in NSCLC. Regulatory effects of NORAD on the proliferative ability of NCI-H1650 and HCC827 cells were evaluated. Dual-luciferase reporter gene assay was conducted to identify the binding between NORAD and miRNA-455, as well as between miRNA-455 and CDK14. At last, the role of NORAD/miRNA-455/CDK14 regulatory loop in influencing the progression of NSCLC was determined.
NORAD was upregulated in NSCLC tissues and cells. Its level was higher in NSCLC patients with advanced stage or accompanied with lymphatic metastasis. Worse prognosis was observed in NSCLC patients presenting high level of NORAD. Silence of NORAD attenuated the proliferative ability of NCI-H1650 and HCC827 cells. MiRNA-455 was the downstream target binding to NORAD. Its level was negatively regulated by NORAD. Knockdown of miRNA-455 could reverse the role of NORAD in regulating the proliferative ability of NSCLC. Moreover, CDK14 was the target gene of miRNA-455. CDK14 level was negatively regulated by miRNA-455.
LncRNA NORAD is upregulated in NSCLC, which enhances the proliferative ability of tumor cells by targeting miRNA-455/CDK14 axis and thereby accelerates the progression of NSCLC.
探讨长链非编码RNA（lncRNA）NORAD在调控非小细胞肺癌（NSCLC）进展中的潜在作用及其可能机制。
检测NSCLC组织和细胞系中NORAD的相对水平。同时检测不同肿瘤分期（T1-T2、T3-T4）及有无淋巴结转移的NSCLC患者中NORAD的水平。绘制Kaplan-Meier曲线以评估NORAD在NSCLC中的预后价值。评估NORAD对NCI-H1650和HCC827细胞增殖能力的调控作用。进行双荧光素酶报告基因实验以鉴定NORAD与miRNA-455之间以及miRNA-455与CDK14之间的结合。最后，确定NORAD/miRNA-455/CDK14调控环在影响NSCLC进展中的作用。
NORAD在NSCLC组织和细胞中上调。在晚期或伴有淋巴结转移的NSCLC患者中其水平更高。NORAD水平高的NSCLC患者预后较差。沉默NORAD可减弱NCI-H1650和HCC827细胞的增殖能力。miRNA-455是与NORAD结合的下游靶点。其水平受NORAD负调控。敲低miRNA-455可逆转NORAD对NSCLC增殖能力的调控作用。此外，CDK14是miRNA-455的靶基因。CDK14水平受miRNA-455负调控。
lncRNA NORAD在NSCLC中上调，通过靶向miRNA-455/CDK14轴增强肿瘤细胞的增殖能力，从而加速NSCLC的进展。
