Ke Shun, Li Rui-Chao, Meng Fan-Kai, Fang Ming-Hao
Department of Emergency Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430030, China.
Department of General Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430030, China.
Aging (Albany NY). 2018 Jan 17;10(1):56-71. doi: 10.18632/aging.101359.
The long non-coding RNA (lncRNA) NKILA (nuclear transcription factor NF-κB interacting lncRNA) functions as a suppressor in human breast cancer and tongue cancer. However, the clinical significance and biological roles of NKILA in esophageal squamous cell carcinoma (ESCC) remain unknown. In this study, we showed that NKILA was downregulated in ESCC tissues and cancer cells compared with their normal counterparts. Low NKILA expression correlated with large tumor size and advanced TNM stage, and predicted poor overall and disease-free survival of ESCC patients. Further loss- and gain-of-function assays indicated that NKILA inhibited proliferation and migration of ESCC cells , suppressed tumor growth and lung metastasis . Mechanistically, NKILA could inhibit phosphorylation of IκBα, suppress p65 nuclear translocation and downregulate the expression of NF-κB target genes in ESCC cells. These results suggest NKILA could suppress malignant development of ESCC via abrogation of the NF-κB signaling and may potentially serve as a prognostic marker for ESCC.
长链非编码RNA(lncRNA)NKILA(核转录因子NF-κB相互作用lncRNA)在人类乳腺癌和舌癌中发挥抑制作用。然而,NKILA在食管鳞状细胞癌(ESCC)中的临床意义和生物学作用尚不清楚。在本研究中,我们发现与正常组织和癌细胞相比,ESCC组织和癌细胞中NKILA表达下调。NKILA低表达与肿瘤体积大及TNM分期晚相关,并预示ESCC患者总体生存率和无病生存率较差。进一步的功能丧失和功能获得实验表明,NKILA抑制ESCC细胞的增殖和迁移,抑制肿瘤生长和肺转移。机制上,NKILA可抑制ESCC细胞中IκBα的磷酸化,抑制p65核转位,并下调NF-κB靶基因的表达。这些结果表明,NKILA可通过废除NF-κB信号通路抑制ESCC的恶性发展,并可能作为ESCC的预后标志物。