miR-452-5p promotes the proliferation, invasion and EMT of esophageal cancer KYSE-150 cells via targeting SOX7 / 中国肿瘤生物治疗杂志

@# [摘 要] 目的：检测miR-452-5p在食管鳞状细胞癌（ESCC）中的表达，并探讨其异常表达对食管癌KYSE-150细胞增殖、侵袭能力和EMT进程的影响及其分子机制。方法：收集2012年3月至2015年12月在河北医科大学第四医院就诊的86名ESCC患者的癌组织样本和对应的癌旁组织，用qPCR法检测miR-452-5p及其他相关基因在ESCC组织和细胞中的表达；向KYSE-150细胞中分别转染miR-452-5p mimic或pcDNA3.1-SOX7构建过表达的细胞株。分析miR-452-5p表达与ESCC病理特征和患者5年OS的关系。用MTS、Tanswell法检测miR-452-5p过表达对食管癌KYSE-150细胞增殖、侵袭能力和EMT进程的影响；用双荧光素酶报告基因实验及TOP/FOP报告基因系统检测miR-452-5p与SRY盒转录因子（SOX7）3'UTR区的结合作用及对Wnt/β-catenin通路活化水平的影响。结果：miR-452-5p在ESCC组织中呈明显高表达（P<0.01），并与ESCC患者的淋巴结转移、TNM分期及5年OS密切相关（均P<0.01）。miR-452-5p过表达明显促进食管癌KYSE-150细胞的增殖、侵袭能力及EMT进程（P<0.05或P<0.01）。SOX7是miR-452-5p的直接靶基因，miR-452-5p通过对SOX7的负向调控影响了Wnt通路活化水平（P<0.05或P<0.01），同时，miR-452-5p表达也受Wnt通路活化水平的影响（P<0.05或P<0.01），其可能为Wnt通路下游靶基因。结论：miR-452-5p通过miR-452-5p/SOX7/Wnt/miR-452-5p正反馈环路提高Wnt/β-catenin通路活化水平，进而促进ESCC KYSE-150细胞的增殖、侵袭能力及EMT进程，miR-452-5p有望成为ESCC患者靶向治疗的潜在靶点及预后评估的新型分子标志物。

Up-regulated miR-452-5p suppressed the expression of RORα and promoted the proliferation and migration of HCC cells / 中国药科大学学报

@#To study the prognosis-related regulation mechanism of miR-452-5p and its influence on the proliferation and migration of hepatocellular carcinoma (HCC) cells, liver hepatocellular carcinoma (LIHC) dataset in The Cancer Genome Atlas (TCGA) was used to validate the differential expression of miR-452-5p and perform the Kaplan-Meier analysis of overall survival (OS).Target genes of miR-452-5p from TargetscanHuman and miRDB databases were predictived; and differentially expressed genes(DEGs) and weighted gene co-expression network analysis (WCGNA) were completed with GSE14520.Lipofectmine-2000 was used to transfect miR-452-5p mimics, mimics negative control, miR-452-5p inhibitor and inhibitor negative control into Huh7 cells,respectively.The mRNA and protein expression level of RORα in 4 groups were determined by RT-qPCR and Western blot.CCK-8 assay and Transwell assay were conducted to testify the capabilities of proliferation and migration.The regulation between miR-452-5p and RORα was confirmed by the dual luciferase reporter assay.After analysis in the TCGA-LIHC dataset, miR-452-5p had higher expression in HCC tissue than that in normal tissue, which was also associated with a shorter OS.RORα and LAMC1 were discriminated by intersecting of DEGs, WGCNA module genes, and predictive target genes.Survival analysis exhibited that dysregulation of RORα was significantly related to the OS.Overexpression of miR-452-5p in HCC cells suppressed the expression of RORα both in mRNA and protein, and also enhanced the viability and migration of HCC cells.The results of the dual luciferase reporter assay showed that miR-452-5p targeted 3′UTR of RORα.Up-regulated miR-452-5p inhibited the expression of RORα, facilitated the proliferation and migration of HCC cells, and promoted the progression and poor prognosis of HCC.

LINC01140 regulates the proliferation and invasion of esophageal squamous cell carcinoma Eca109 cells via miR-452-5p/Wnt/β-catenin axis / 中国肿瘤生物治疗杂志

@# [摘 要] 目的： 探讨长链非编码RNA（lncRNA）LINC01140在食管鳞状细胞癌（esophageal squamous cell carcinoma，ESCC）组织及细胞中的表达及其对Eca109细胞增殖与侵袭的影响及其分子机制。方法：选取2012年3月至2015年5月河北医科大学第四医院收治的133例ESCC患者的临床资料和GEPIA数据库中收集的182例ESCC组织及286例食管正常黏膜组织的LINC01140表达数据，以及ESCC细胞系Kyse150、Eca109和TE13。用qPCR法检测癌组织和细胞中LINC01140的表达水平，分析其表达水平与患者临床病理特征及预后的关系。分别将pcDNA3.1-LINC01140、阴性对照（pcDNA3.1-NC）或miR-452-5p mimic及阴性对照（miR-NC）转染到Eca109细胞，MTS、Transwell实验分别检测细胞的增殖与侵袭能力。用双荧光报告基因实验及TOP/FOP报告基因系统检测LINC01140与miR-452-5p的靶向结合作用及LINC01140对Wnt/β-catenin通路活化水平的影响。结果：LINC01140在ESCC组织和细胞中表达均显著下调（均P<0.01），LINC01140低表达与ESCC患者年龄、淋巴结转移、TNM分期及OS密切相关（均P<0.05）。LINC01140过表达明显抑制Eca109细胞的增殖及侵袭能力（均P<0.01）。机制研究表明，LINC01140可能通过竞争结合miR-452-5p影响Wnt/β-catenin信号通路的活化水平继而调控Eca109细胞的恶性生物学行为。结论：LINC01140通过靶向miR-452-5p/Wnt/β-catenin轴促进ESCC细胞的增殖与侵袭能力，其有望成为ESCC患者靶向治疗的潜在靶点及预后评估的标志物。