Long non-coding RNA 00607 as a tumor suppressor by modulating NF-κB p65/p53 signaling axis in hepatocellular carcinoma
Long non-coding RNA 00607 as a tumor suppressor by modulating NF-κB p65/p53 signaling axis in hepatocellular carcinoma
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长非编码 RNA00607 通过调节肝细胞癌中的 NF-kappaB p65/p53 信号轴作为肿瘤抑制因子。
DOI：
10.1093/carcin/bgy113
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发表时间：
2018-12-01
期刊：
影响因子：
4.7
通讯作者：
Fan, Jia
中科院分区：
文献类型：
--
作者：
Sun, Qi-Man;Hu, Bo;Fan, Jia
越来越多的证据表明，长链非编码RNA（lncRNA）在某些恶性肿瘤中起着重要作用。然而，lncRNA如何调控肝细胞癌（HCC）过程的机制仍不清楚。在这项研究中，我们探讨了lncRNA 00607作为一种新的肿瘤抑制因子在肝癌中的潜在作用。在这项研究中，我们研究了重要的炎症细胞因子肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）对lncRNA 00607的调节。我们还测定了LINC 000607在159个HCC肿瘤和配对的邻近组织中的表达。在体外HCC细胞系和体内肿瘤异种移植物中检查LINC 000607在HCC增殖和凋亡中的作用。此外，我们还研究了lncRNA 00607调节NF-κ B p65的潜在机制以及LIN 00607如何在HCC中发挥其肿瘤抑制作用。我们发现lncRNA 00607在HCC肿瘤中的表达水平低于相匹配的正常肝组织，并且其低表达预示HCC预后较差。在功能上，lncRNA 00607过表达导致体外和体内HCC细胞增殖降低，细胞凋亡和化疗药物敏感性增强。从机制上讲，lncRNA 00607通过结合p65启动子区域抑制p65转录，因此有助于HCC中p53水平的增加。总之，本研究的发现表明TNF-α/IL-6-lncRNA 00607-NF-κ B p65/p53信号传导轴代表了癌症化疗中的新治疗途径。
Accumulating evidence suggests that long non-coding RNA (lncRNA) plays important roles in some malignant tumors. However, the mechanism underlying how lncRNA regulates hepatocellular carcinoma (HCC) process remains largely unknown. In this study, we explored the potential role of lncRNA 00607 as a novel tumor suppressor in HCC. In this study, we examined the regulation of lncRNA 00607 by the important inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). We also determined the expression of LINC000607 in 159 HCC tumors and paired adjacent tissues. Effects of LINC000607 in HCC proliferation and apoptosis were examined in vitro in HCC cell lines and in vivo tumor xenografts. Furthermore, we also examine underlying mechanism by which lncRNA 00607 regulates NF-kappa B p65 and how LIN00607 exerts its tumor suppressor role in HCC. We found that lncRNA 00607 expression level is lower in HCC tumors compared with matched normal liver tissue, and its low expression predicts worse prognosis in HCC. Functionally, lncRNA 00607 overexpression leads to decreased HCC cell proliferation in vitro and in vivo, enhanced apoptosis and chemotherapeutic drug sensitivity. Mechanistically, lncRNA 00607 inhibits the p65 transcription by binding to the p65 promoter region, therefore contributing to increased p53 levels in HCC. Taken together, the findings of this study show that the TNF-alpha/IL-6-lncRNA 00607-NF-kappa B p65/p53 signaling axis represents a novel therapeutic avenue in cancer chemotherapy.