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A novel long noncoding RNA, LOC440173, promotes the progression of esophageal squamous cell carcinoma by modulating the miR-30d-5p/HDAC9 axis and the epithelial-mesenchymal transition

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机构: [1]Hebei Med Univ, Hosp 4, Hebei Canc Inst, Dept Lab Pathol, Jiankang Rd 12, Shijiazhuang 050011, Hebei, Peoples R China [2]Hebei Med Univ, Hosp 4, Dept Expt Anim Ctr, Shijiazhuang, Hebei, Peoples R China
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关键词: esophageal squamous cell carcinoma LOC440173 long noncoding RNA therapeutics tumorigenesis

摘要:
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.

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出版当年[2020]版:
大类 | 2 区 医学
小类 | 3 区 生化与分子生物学 3 区 肿瘤学
最新[2025]版:
大类 | 4 区 医学
小类 | 3 区 生化与分子生物学 4 区 肿瘤学
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出版当年[2020]版:
Q2 ONCOLOGY Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
最新[2023]版:
Q2 ONCOLOGY Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

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第一作者机构: [1]Hebei Med Univ, Hosp 4, Hebei Canc Inst, Dept Lab Pathol, Jiankang Rd 12, Shijiazhuang 050011, Hebei, Peoples R China
通讯作者:
通讯机构: [1]Hebei Med Univ, Hosp 4, Hebei Canc Inst, Dept Lab Pathol, Jiankang Rd 12, Shijiazhuang 050011, Hebei, Peoples R China [*1]Department of Laboratory of Pathology, Hebei Cancer Institute, the Fourth Hospital of Hebei Medical University, Jiankang Rd. 12, Shijiazhuang, 050011 Hebei Province, China.
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