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长链非编码 RNA ADAMTS9-AS1 敲低抑制非小细胞肺癌细胞增殖和 EMT。

LncRNA ADAMTS9-AS1 knockdown restricts cell proliferation and EMT in non-small cell lung cancer.

机构信息

Department of Oncology, The Second Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, PR China.

出版信息

Histol Histopathol. 2021 Oct;36(10):1063-1072. doi: 10.14670/HH-18-347. Epub 2021 Jun 4.

Abstract

A recent bioinformatics analysis identified long non-coding RNA antisense 1 ADAMTS9-AS1 as an independent prognostic marker in several tumors, including prostate cancer and bladder cancer. Nevertheless, the prognostic value and functional role of ADAMTS9-AS1 in non-small cell lung cancer (NSCLC) remain elusive. Here, we first found that the expression of ADAMTS9-AS1 was significantly upregulated in NSCLC tissues compared with adjacent normal tissues using quantitative real time PCR analysis. Clinically, we observed that ADAMTS9-AS1 expression was associated with TNM stage, lymph node metastasis and poor prognosis in NSCLC patients. By performing loss-of-function assay in A549 and 95D cells, our in vitro experiments further showed that knockdown of ADAMTS9-AS1 remarkedly suppressed cell proliferation, caused cell cycle G0/G1 arrest and apoptosis, and inhibited cell migration and invasion in NSCLC cells using CCK-8, colony formation, flow cytometry and transwell assays. Moreover, we found that ADAMTS9-AS1 knockdown downregulated the expression of CDK4, N-cadherin, Vimentin, but upregulated the expression of Bad and E-cadherin. In summary, our results revealed that ADAMTS9-AS1 may serve as a potential therapeutic target for the treatment of patients with NSCLC.

摘要

最近的一项生物信息学分析确定长非编码 RNA 反义 1 ADAMTS9-AS1 是几种肿瘤(包括前列腺癌和膀胱癌)的独立预后标志物。然而,ADAMTS9-AS1 在非小细胞肺癌(NSCLC)中的预后价值和功能作用仍不清楚。在这里,我们首次使用定量实时 PCR 分析发现,ADAMTS9-AS1 在 NSCLC 组织中的表达明显高于相邻正常组织。临床上,我们观察到 ADAMTS9-AS1 的表达与 NSCLC 患者的 TNM 分期、淋巴结转移和不良预后相关。通过在 A549 和 95D 细胞中进行功能丧失测定,我们的体外实验进一步表明,ADAMTS9-AS1 的敲低显著抑制 NSCLC 细胞的增殖,导致细胞周期 G0/G1 期阻滞和细胞凋亡,并通过 CCK-8、集落形成、流式细胞术和 Transwell 测定抑制细胞迁移和侵袭。此外,我们发现 ADAMTS9-AS1 的敲低下调了 CDK4、N-钙黏蛋白、波形蛋白的表达,但上调了 Bad 和 E-钙黏蛋白的表达。总之,我们的结果表明,ADAMTS9-AS1 可能成为治疗 NSCLC 患者的潜在治疗靶点。

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