Countless evidence suggests that long noncoding RNAs (lncRNAs) are involved in human malignant cancers, including esophageal squamous cell carcinoma (ESCC), although their exact function remains unclear. In the present study, we aimed to investigate the roles and molecular mechanisms of the lncRNA LOC440173 in ESCC progression. Microarray analysis and quantitative real‐time polymerase chain reaction were conducted to measure the expression levels of LOC440173 and miR‐30d‐5p. The biological function of this lncRNA was investigated using the 3‐(4,5‐dimethylthiazol‐2‐yl)‐5‐(3‐carboxymethoxyphenyl)‐2‐(4‐sulfophenyl)‐2H‐tetrazolium, clone formation, and transwell assays, as well as flow cytometry and Western blot analysis. The function of LOC440173 was validated in vivo using tumor xenografts. The regulatory network of LOC440173/miR‐30d‐5p/HDAC9 was established using bioinformatic analysis and verified with dual‐luciferase reporter assays, RNA immunoprecipitation assay, and rescue experiments. The expression level of LOC440173 was significantly increased in ESCC tissues and esophageal carcinoma cells. High LOC440173 expression was correlated with histological grade, tumor invasion depth, lymph node metastasis, and TNM stage. Overexpression of LOC440173 promoted esophageal cancer cell proliferation, migration, and invasion, as well as the epithelial–mesenchymal transition (EMT) process in vitro, and facilitated tumor growth in vivo. MicroRNA‐30d‐5p (miR‐30d‐5p) was downregulated in ESCC tissues and acted as a direct binding target of LOC440173 during the regulation of HDAC9 expression in esophageal carcinoma cells. In conclusion, LOC440173 exerts a promotive role in ESCC tumorigenesis by targeting the miR‐30d‐5p/HDAC9 axis and regulating the EMT process. LOC440173 might be a new therapeutic target for the treatment of ESCC.

中文翻译：

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新型长非编码RNA LOC440173通过调节miR-30d-5p / HDAC9轴和上皮-间质转化促进食管鳞状细胞癌的发展

无数证据表明，长的非编码RNA（lncRNA）与人类恶性肿瘤有关，包括食道鳞状细胞癌（ESCC），尽管其确切功能尚不清楚。在本研究中，我们旨在研究lncRNA LOC440173在ESCC进展中的作用和分子机制。进行了微阵列分析和定量实时聚合酶链反应以测量LOC440173和miR-30d-5p的表达水平。使用3-（4,5-二甲基噻唑-2-基）-5-（3-羧基甲氧基苯基）-2-（4-磺基苯基）-2H-四氮唑，克隆形成和Transwell分析法研究了该lncRNA的生物学功能，以及流式细胞仪和Western blot分析。使用肿瘤异种移植物在体内验证了LOC440173的功能。LOC440173 / miR-30d-5p / HDAC9的调控网络是通过生物信息学分析建立的，并通过双荧光素酶报告基因测定，RNA免疫沉淀测定和拯救实验进行了验证。在食管鳞癌组织和食管癌细胞中LOC440173的表达水平显着升高。LOC440173高表达与组织学分级，肿瘤浸润深度，淋巴结转移和TNM分期相关。LOC440173的过表达在体外促进食管癌细胞的增殖，迁移和侵袭，以及上皮-间质转化（EMT）过程，并促进体内肿瘤的生长。在食管癌细胞中调控HDAC9表达的过程中，ESCA组织中的MicroRNA-30d-5p（miR-30d-5p）被下调，并成为LOC440173的直接结合靶标。结论，LOC440173通过靶向miR-30d-5p / HDAC9轴并调节EMT过程在ESCC肿瘤发生中发挥促进作用。LOC440173可能是ESCC的新治疗靶标。