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抑癌长链非编码 RNA AF118081 在抗苯并[a]芘-反-7,8-二氢二醇-9,10-环氧化物转化 16HBE 细胞中的作用。

Oncogenic role of long noncoding RNA AF118081 in anti-benzo[a]pyrene-trans-7,8-dihydrodiol-9,10-epoxide-transformed 16HBE cells.

机构信息

Institute for Chemical Carcinogenesis, State Key Laboratory for Respiratory Diseases, Guangzhou Medical University, Guangzhou 510182, PR China.

Department of Thoracic Surgery, General Hospital of Guangzhou Military Command of Chinese People's Liberation Army, Guangzhou 510010, PR China.

出版信息

Toxicol Lett. 2014 Sep 17;229(3):430-9. doi: 10.1016/j.toxlet.2014.07.004. Epub 2014 Jul 19.

Abstract

Lung cancer is the leading cause of cancer deaths and remains an important public health problem worldwide. Long noncoding RNAs (lncRNAs) are newly identified regulators of tumorigenesis and tumor progression. However, the role of lncRNAs in lung cancer induced by environmental carcinogens remains largely unknown. In this study, an lncRNA microarray was used to compare the expression profiles of malignantly transformed 16HBE cells (16HBE-T) induced with anti-benzo[a]pyrene-trans-7,8-diol-9,10-epoxide (anti-BPDE) and normal 16HBE cells (16HBE-N). Using quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR), lncRNA AF118081 was identified as the most significantly overexpressed lncRNA in 16HBE-T cells, lung cancer cells, and patient samples. Cell proliferation, colony formation, apoptosis, migration, and invasion were assayed in 16HBE-T cells following the knockdown of lncRNA AF118081 with small interfering RNA. AF118081 knockdown inhibited cell growth and tumor invasion. An in vivo (nude mouse) model was then used to assay tumor growth, and the downregulation of AF118081 clearly suppressed tumor growth, consistent with the results of the in vitro assays. Together, these findings identify a new oncogenic lncRNA, lncRNA AF118081, in malignantly transformed 16HBE cells. This enhances our understanding of lncRNAs as important regulatory elements in chemical carcinogenesis and potential targets of lung cancer therapies.

摘要

肺癌是癌症死亡的主要原因,仍然是全球重要的公共卫生问题。长链非编码 RNA(lncRNA)是新发现的肿瘤发生和肿瘤进展的调节因子。然而,lncRNA 在环境致癌物诱导的肺癌中的作用在很大程度上尚不清楚。在这项研究中,使用 lncRNA 微阵列比较了经抗苯并[a]芘-trans-7,8-二氢二醇-9,10-环氧化物(anti-BPDE)诱导的恶性转化 16HBE 细胞(16HBE-T)与正常 16HBE 细胞(16HBE-N)的表达谱。使用实时定量逆转录聚合酶链反应(qRT-PCR),鉴定出 lncRNA AF118081 在 16HBE-T 细胞、肺癌细胞和患者样本中表达最为显著上调。用小干扰 RNA 敲低 lncRNA AF118081 后,在 16HBE-T 细胞中检测细胞增殖、集落形成、细胞凋亡、迁移和侵袭。AF118081 敲低抑制细胞生长和肿瘤侵袭。然后使用体内(裸鼠)模型检测肿瘤生长,AF118081 的下调明显抑制肿瘤生长,与体外实验结果一致。总之,这些发现确定了一种新的致癌 lncRNA,lncRNA AF118081,在恶性转化的 16HBE 细胞中。这增强了我们对 lncRNA 作为化学致癌作用中重要调节因子的理解,并为肺癌治疗提供了潜在的靶点。

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