长链非编码 RNA AB073614 通过 PI3K/AKT 信号通路调节结直肠癌细胞的增殖和转移。
LncRNA AB073614 regulates proliferation and metastasis of colorectal cancer cells via the PI3K/AKT signaling pathway.
机构信息
Department of Laboratory, The Fifth Affiliated Hospital, Sun Yat-sen University, No.52 Mei Hua East Road, Zhuhai 519000, Guangdong, PR China.
Department of General Surgery, The Fifth Affiliated Hospital, Sun Yat-sen University, No.52 Mei Hua East Road, Zhuhai 519000, Guangdong, PR China.
出版信息
Biomed Pharmacother. 2017 Sep;93:1230-1237. doi: 10.1016/j.biopha.2017.07.024. Epub 2017 Jul 20.
The expression profiles of long noncoding RNAs (lncRNAs) in colorectal cancer (CRC) have remained unclear. LncRNA AB073614 is known to be upregulated in ovarian cancer and glioma tissues, and is associated with the occurrence and progression of those cancers. In the present study, we investigated the lncRNA AB073614 gene expression patterns in CRC cell lines and tissue samples from CRC patients, and then analyzed them for possible associations with various clinicopathological characteristics. Furthermore, the roles played by lncRNA AB073614 in CRC cell proliferation, apoptosis, cell cycle progression, migration, and invasion were examined in vitro by using gene knockdown and overexpression techniques. We detected the levels of lncRNA AB073614 in 28 paired CRC tissues and adjacent normal tissues by qRT-PCR, and our results revealed that AB073614 expression in 85.7% (24/28) of the CRC tissues was significantly higher than those in the paired normal tissues. Furthermore, the levels of AB073614 were closely related to tumor grade, size, cell differentiation status, and the presence of distant metastases. Knockdown of AB073614 expression significantly inhibited the proliferation, migration, and invasion of SW480 cells, and resulted in their increased rates of apoptosis and G1 phase cell cycle arrest, whereas overexpression of AB073614 produced the opposite effects. Finally, results of studies which used an agonist (740Y-P) and an inhibitor (LY294002) of the PI3K/AKT signaling pathway, as well as the results of western blot assays, indicated that lncRNA AB073614 exerts its effects by targeting the PI3K/AKT-mediated signaling pathway. Taken together, our data indicate that lncRNA AB073614 acts to prevent CRC progression by affecting the PI3K/AKT signaling pathway, and may be useful as a novel prognostic or treatment agent for CRC.
长链非编码 RNA(lncRNA)在结直肠癌(CRC)中的表达谱尚不清楚。已知 lncRNA AB073614 在卵巢癌和神经胶质瘤组织中上调,并与这些癌症的发生和进展有关。在本研究中,我们研究了 CRC 细胞系和 CRC 患者组织样本中 lncRNA AB073614 基因的表达模式,并分析了它们与各种临床病理特征的可能关联。此外,我们还通过基因敲低和过表达技术,在体外研究了 lncRNA AB073614 在 CRC 细胞增殖、凋亡、细胞周期进程、迁移和侵袭中的作用。我们通过 qRT-PCR 检测了 28 对 CRC 组织和相邻正常组织中的 lncRNA AB073614 水平,结果显示,28 例 CRC 组织中 85.7%(24/28)的 AB073614 表达明显高于配对正常组织。此外,AB073614 的水平与肿瘤分级、大小、细胞分化状态和远处转移密切相关。AB073614 表达的敲低显著抑制了 SW480 细胞的增殖、迁移和侵袭,并导致其凋亡率增加和 G1 期细胞周期阻滞,而过表达 AB073614 则产生相反的效果。最后,使用 PI3K/AKT 信号通路激动剂(740Y-P)和抑制剂(LY294002)以及 Western blot 检测的研究结果表明,lncRNA AB073614 通过靶向 PI3K/AKT 介导的信号通路发挥作用。综上所述,我们的数据表明,lncRNA AB073614 通过影响 PI3K/AKT 信号通路来防止 CRC 的进展,并且可能作为 CRC 的一种新的预后或治疗剂。