Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China; Department of Thoracic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China.
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China; Department of Anesthesiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China.
Cancer Lett. 2019 Sep 28;460:18-28. doi: 10.1016/j.canlet.2019.06.009. Epub 2019 Jun 15.
Accumulating evidence indicates that CCL18 and the long non-coding RNA, HOTAIR, have critical roles in cancer progression and metastasis, but the correlation between CCL18 and HOTAIR in esophageal squamous cell carcinoma (ESCC) and their downstream molecular mechanisms remain unclear. Overexpression of CCL18 in ESCC tissues was associated with a worse survival in patients with ESCC. CCL18 enhanced the invasiveness of ESCC cells in a dose-dependent manner, whereas CCL18 knockdown inhibited their invasiveness. In particular, CCL18 expression was positively associated with HOTAIR expression in ESCC tissues. Furthermore, CCL18 upregulated the expression of HOTAIR, and knockdown of HOTAIR alleviated the CCL18-induced invasiveness of ESCC cells. HOTAIR may act as a competing endogenous RNA and could effectively becoming a sponge for miR-130a-5p, thereby modulating the derepression of ZEB1 and promoting epithelial-mesenchymal transition in ESCC. Our study suggests that CCL18 contributes to the malignant progression of esophageal cancer by upregulating HOTAIR expression. HOTAIR overexpression may promote tumor invasiveness and progression in ESCC, given that HOTAIR functions as a miR-130a-5p sponge, positively regulating ZEB1. This provides new therapeutic targets for early diagnosis and treatment of ESCC.
越来越多的证据表明，CCL18 和长链非编码 RNA HOTAIR 在癌症的进展和转移中具有关键作用，但 CCL18 和 HOTAIR 在食管鳞状细胞癌（ESCC）中的相关性及其下游分子机制仍不清楚。ESCC 组织中 CCL18 的过表达与 ESCC 患者的生存预后较差有关。CCL18 以剂量依赖性方式增强 ESCC 细胞的侵袭性，而 CCL18 敲低则抑制其侵袭性。特别是，CCL18 的表达与 ESCC 组织中 HOTAIR 的表达呈正相关。此外，CCL18 上调 HOTAIR 的表达，而 HOTAIR 的敲低减轻了 CCL18 诱导的 ESCC 细胞侵袭性。HOTAIR 可能作为竞争内源性 RNA，可有效地作为 miR-130a-5p 的海绵，从而调节 ZEB1 的去抑制，并促进 ESCC 中的上皮-间充质转化。我们的研究表明，CCL18 通过上调 HOTAIR 的表达促进食管癌的恶性进展。鉴于 HOTAIR 作为 miR-130a-5p 的海绵，正向调节 ZEB1，HOTAIR 的过表达可能会促进 ESCC 的肿瘤侵袭和进展。这为 ESCC 的早期诊断和治疗提供了新的治疗靶点。
