MYC 靶向长链非编码 RNA MINCR 在非小细胞肺癌细胞周期调控和细胞凋亡中的作用。
Roles of MYC-targeting long non-coding RNA MINCR in cell cycle regulation and apoptosis in non-small cell lung Cancer.
机构信息
Department of Cardiothoracic Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang, 212001, Jiangsu Province, China.
School of Medicine, Jiangsu University, Zhenjiang, 212013, Jiangsu Province, China.
出版信息
Respir Res. 2019 Sep 3;20(1):202. doi: 10.1186/s12931-019-1174-z.
BACKGROUND
Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer death in the world, and has a relatively low survival rate. Long non-coding RNAs (lncRNAs) have been demonstrated to modulate cancer progression through a variety of molecular mechanisms. We sought to investigate the role and potential mechanism of MYC-induced long non-coding RNA (MINCR) in NSCLC.
METHODS
Expression levels of MINCR was first identified using The Cancer Genome Atlas (TCGA), further confirmed with specimens from 29 NSCLC patients and three cell lines using qRT-PCR. Overexpression and knockdown of MINCR were performed in NSCLC cell lines through MINCR overexpression vectors and synthesized siRNAs, respectively. The roles of MINCR in NSCLC cell lines, such as cell proliferation, cell cycle arrest, and apoptosis, were identified by MTT, flow cytometry, and Western blot. The modulation of MINCR-regulated genes, including c-Myc and its downstream effectors, as well as apoptosis-associated genes, was analyzed using Western blot.
RESULTS
MINCR expression was increased in NSCLC patients from TCGA datasets, and was also significantly increased in our collected specimens from NSCLC patients and NSCLC cell lines. Knocking down of MINCR greatly inhibited the growth of NSCLC cell lines PC9 and A549. In addition, silencing of MINCR induced cell cycle arrest and apoptosis. Furthermore, silencing of MINCR reduced the expression levels of oncogene c-Myc and its downstream cyclin A, cyclin D, CD4, and CDK2, as well as apoptosis-associated Bcl-2, while significantly increased the expression levels of cleaved PARP-1. In the meantime, overexpression of MINCR remarkably enhanced cell proliferation of PC9 cells and activated c-Myc and its downstream effectors.
CONCLUSION
MINCR exerted inhibitory effects on the cell cycle arrest and apoptosis of NSCLC cells by activating c-Myc and its downstream effectors, suggesting that this lncRNA could be used as a potential therapeutic target for the treatment of NSCLC.
背景
非小细胞肺癌（NSCLC）是世界上癌症死亡的主要原因之一，其生存率相对较低。长链非编码 RNA（lncRNA）已被证明通过多种分子机制调节癌症的进展。我们试图研究 MYC 诱导的长链非编码 RNA（MINCR）在 NSCLC 中的作用和潜在机制。
方法
首先使用癌症基因组图谱（TCGA）鉴定 MINCR 的表达水平，然后使用来自 29 名 NSCLC 患者和三个细胞系的标本通过 qRT-PCR 进一步证实。通过 MINCR 过表达载体和合成的 siRNA 分别在 NSCLC 细胞系中过表达和敲低 MINCR。通过 MTT、流式细胞术和 Western blot 鉴定 MINCR 在 NSCLC 细胞系中的作用，如细胞增殖、细胞周期停滞和细胞凋亡。通过 Western blot 分析 MINCR 调节基因，包括 c-Myc 及其下游效应物以及凋亡相关基因的调控。
结果
TCGA 数据集显示 NSCLC 患者中 MINCR 的表达增加，我们从 NSCLC 患者和 NSCLC 细胞系中收集的标本中也显著增加。MINCR 的敲低极大地抑制了 NSCLC 细胞系 PC9 和 A549 的生长。此外，沉默 MINCR 诱导细胞周期停滞和细胞凋亡。此外，沉默 MINCR 降低了癌基因 c-Myc 及其下游周期蛋白 A、周期蛋白 D、CD4 和 CDK2 的表达水平，以及凋亡相关的 Bcl-2，同时显著增加了裂解的 PARP-1 的表达水平。同时，MINCR 的过表达显著增强了 PC9 细胞的细胞增殖，并激活了 c-Myc 及其下游效应物。
结论
MINCR 通过激活 c-Myc 及其下游效应物对 NSCLC 细胞的细胞周期停滞和凋亡发挥抑制作用，表明这种 lncRNA 可作为 NSCLC 治疗的潜在治疗靶点。
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