KLF15 promotes the proliferation and metastasis of lung adenocarcinoma cells and has potential as a cancer prognostic marker.
KLF15 promotes the proliferation and metastasis of lung adenocarcinoma cells and has potential as a cancer prognostic marker.
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DOI：
10.18632/oncotarget.21972
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发表时间：
2017-12-15
期刊：
影响因子：
--
通讯作者：
Bian T
中科院分区：
文献类型：
--
作者：
Gao L;Qiu H;Liu J;Ma Y;Feng J;Qian L;Zhang J;Liu Y;Bian T
肺腺癌(LADC)是一种常见的非小细胞肺癌，对世界范围内的公众健康构成重大威胁。LADC的5年存活率目前低于15%。转录因子KLF15，也被称为肾脏富集型KLF(KKLF)，已被证明在抑制包括子宫内膜、胰腺和乳腺在内的癌细胞的增殖和多样化方面发挥作用，但KLF15参与LADC的研究尚未见报道。在这项研究中，我们比较了KLF15在人LADC组织和邻近正常肺组织中的体外表达。KLF15在LADC组织和细胞中的表达明显高于癌旁非肿瘤组织，且与肿瘤的临床分期和分化程度有关(P=0.003，P=0.001)。通过Western blotting、CCK8和集落形成实验、流式细胞仪和跨孔迁移实验，以及体内成瘤实验，观察KLF15对细胞生长和迁移的影响。KLF15基因敲除可显著上调caspase-3、caspase-7、caspase-8和PARP的蛋白水平，从而诱导细胞凋亡。KLF15在A549和NCI-H1650细胞系中的表达下调，导致这些细胞系在裸鼠侧部皮下注射时，与对照组相比，其生长速度明显减慢(P<；0.05)。总之，我们的研究结果表明，KLF15可能对LADC细胞的存活有显著影响，它可能是LADC预后和治疗的潜在的治疗和预防生物标志物。
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 in vitro 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 (P = 0.003, P = 0.001, respectively). The effect of KLF15 on cell growth and migration were explored in vitro by Western Blotting, CCK8 and colony formation assays, flow cytometry analysis and transwell migration assays, and in vivo 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 (P < 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.
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影响因子：
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作者：
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作者：
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发表时间：
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影响因子：
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作者：
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