Department of Thoracic Surgery, Shanghai Key Laboratory of Clinical Geriatric Medicine, HuaDong Hospital, FuDan University, Shanghai, China.
Eur Rev Med Pharmacol Sci. 2020 May;24(10):5446-5455. doi: 10.26355/eurrev_202005_21329.
Non-small cell lung cancer (NSCLC) accounts for the majority of lung cancer, with an unfavorable prognosis of 5-year survival rates. It is of great clinical significance to further search for more efficacious and novel targets for diagnosis and therapeutic strategies. This study aimed at clarifying the role of long non-coding RNA (lncRNA) NORAD in proliferation, invasion and migration and tumor growth of NSCLC.
In this study, mRNA levels of lncRNA NORAD were examined by RT-PCR. CCK-8 assay was applied to test cell viability. Furthermore, wound healing assay and transwell assay were performed to detect the migration and invasion of A549 cells, respectively. Immunohistochemistry was applied to assess the levels of CXC chemokine receptor (CXCR) 4 and CXC chemokine ligand (CXCL) 12. Mice models of NSCLC in vivo were exploited to further examine the potential role of NORAD in tumor growth. Key proteins related to Ras homolog gene family member A (RhoA) GTPase/Rho-associated kinase (RhoA/ROCK) pathway were determined by Western blot.
NORAD has elevated the levels in NSCLC tissues and cells. NORAD interference dramatically inhibited tumor growth and suppressed A549 cell proliferation, migration and invasion by downregulating CXCR4 and CXCL12 expression. RhoA/ROCK signaling pathway was activated in NSCLC.
This study revealed that the downregulation of lncRNA NORAD could slow down the progression of NSCLC by regulating CXCR4 and RhoA/ROCK signaling pathway.
非小细胞肺癌（NSCLC）占肺癌的大多数，其 5 年生存率预后不佳。进一步寻找更有效和新颖的诊断和治疗策略靶点具有重要的临床意义。本研究旨在阐明长链非编码 RNA（lncRNA）NORAD 在非小细胞肺癌增殖、侵袭和迁移以及肿瘤生长中的作用。
本研究通过 RT-PCR 检测 lncRNA NORAD 的 mRNA 水平。CCK-8 检测细胞活力。此外，还进行了划痕愈合实验和 Transwell 实验分别检测 A549 细胞的迁移和侵袭。免疫组织化学法检测 CXC 趋化因子受体（CXCR）4 和 CXC 趋化因子配体（CXCL）12 的水平。利用 NSCLC 小鼠模型体内进一步研究 NORAD 在肿瘤生长中的潜在作用。Western blot 检测与 Ras 同源基因家族成员 A（RhoA）GTP 酶/Rho 相关激酶（RhoA/ROCK）通路相关的关键蛋白。
NORAD 在 NSCLC 组织和细胞中上调。NORAD 干扰通过下调 CXCR4 和 CXCL12 表达，显著抑制肿瘤生长并抑制 A549 细胞增殖、迁移和侵袭。RhoA/ROCK 信号通路在 NSCLC 中被激活。
本研究表明，下调 lncRNA NORAD 可通过调节 CXCR4 和 RhoA/ROCK 信号通路来减缓 NSCLC 的进展。
