Gao Lihua, Qiu Hongmei, Liu Jian, Ma Yuzhen, Feng Jia, Qian Li, Zhang Jianguo, Liu Yifei, Bian Tingting
Department of Oncology, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China.
Department of Respiration, Nantong Geriatric Rehabilitation Hospital, Branch of Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China.
Oncotarget. 2017 Oct 19;8(66):109952-109961. doi: 10.18632/oncotarget.21972. eCollection 2017 Dec 15.
Lung adenocarcinoma (LADC)is a general form of non-small cell lung cancer that represents a significant threat to public health worldwide. The 5-year-survival rate for LADC is currently below 15%. The transcription factor KLF15, also called kidney-enriched KLF (KKLF), has been proven to play a role in inhibiting proliferation and diversification of carcinoma cells, including those of the endometrium, pancreas and breast, but the involvement of KLF15 in LADC has not previously been studied. In this study, we compared the expression of KLF15 in human LADC tissues and adjacent normal lung tissues. Expression of KLF15 was found to be abnormally high in LADC tissues and cells compared with adjacent non-tumorous tissues, and was correlated with tumor TNM stage and tumor differentiation ( = 0.003, = 0.001, respectively). The effect of KLF15 on cell growth and migration were explored by Western Blotting, CCK8 and colony formation assays, flow cytometry analysis and transwell migration assays, and by analysis of tumorigenesis in 5-week old BALB/c nude mice. Knockdown of KLF15 significantly upregulated the protein levels of cleaved caspase-3, caspase-7, caspase-8 and PARP, thereby inducing apoptosis. Downregulation of KLF15 in A549 and NCI-H1650 cell lines resulted in these cell lines exhibiting markedly slower growth rates when injected subcutaneously into the flank of nude mice, compared with the comparator control groups ( < 0.05). Collectively, our findings suggest that KLF15 may have a significant effect on LADC cell survival, and that it represents a potential therapeutic and preventive biomarker for LADC prognosis and treatment.
肺腺癌（LADC）是一种非小细胞肺癌的常见类型，对全球公众健康构成重大威胁。目前LADC的5年生存率低于15%。转录因子KLF15，也称为肾富集KLF（KKLF），已被证明在抑制癌细胞（包括子宫内膜癌、胰腺癌和乳腺癌细胞）的增殖和分化中发挥作用，但此前尚未研究过KLF15在LADC中的作用。在本研究中，我们比较了KLF15在人LADC组织和相邻正常肺组织中的表达。与相邻的非肿瘤组织相比，发现KLF15在LADC组织和细胞中的表达异常高，并且与肿瘤TNM分期和肿瘤分化相关（分别为 = 0.003， = 0.001）。通过蛋白质免疫印迹法、CCK8和集落形成试验、流式细胞术分析和Transwell迁移试验，以及通过对5周龄BALB/c裸鼠肿瘤发生情况的分析，探讨了KLF15对细胞生长和迁移的影响。敲低KLF15可显著上调裂解的caspase-3、caspase-7、caspase-8和PARP的蛋白水平，从而诱导细胞凋亡。与对照对照组相比，在A549和NCI-H1650细胞系中下调KLF15后，将这些细胞系皮下注射到裸鼠侧腹时，其生长速度明显减慢（ < 0.05）。总体而言，我们的研究结果表明，KLF15可能对LADC细胞存活有显著影响，并且它代表了LADC预后和治疗的潜在治疗和预防生物标志物。
