BACKGROUND:Long non-coding RNAs (lncRNAs) are powerful factors influencing the tumorigenesis and metastasis of multiple carcinomas. LncRNA MNX1-AS1 plays critical roles in the progression of tumor formation according to recent research, while its roles in esophageal squamous cell carcinoma (ESCC) remains unknown.METHODS:The expression levels of lncRNA MNX1-AS1 were examined in ESCC tissues by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). The role of lncRNA MNX1-AS1 was performed by WST-1 proliferation assays, migration and invasion assays. Besides, the molecular mechanism of lncRNA MNX1-AS1 was verified by online bioinformatics, qRT-PCR and rescue assays.RESULTS:MNX1-AS1 was signifcantly upregulated in ESCC tissues. It was conformed that high MNX1-AS1 expression was associated with ESCC lymph node metastasis. Moreover, we found that knockdown of MNX1-AS1 apparently suppressed the cell proliferation, migration, and invasion capacity. Flow cytometry analysis showed MNX1-AS1 regulated ESCC cell cycle and apoptosis progression. Mechanism analysis revealed that miR-34a inhibitor could rescue the influence of inhibiting MNX1-AS1 on ESCC cells migration by serving as competing endogenous RNA (ceRNAs). Furthermore, we found that miR-34a specifically targeted SIRTI.CONCLUSIONS:Taken together, we demonstrated that lncRNA MNX1-AS1/miR-34a/SIRT1 regulatory axis could play an important role in ESCC progression, and MNX1-AS1 may act as a novel potential biomarker for esophageal squamous cell carcinoma.

目的 观察食管鳞癌(ESCC)患者血浆长链非编码RNA(lncRNA) TUC338表达变化,并探讨其诊断ESCC的潜在价值.方法 选择ESCC患者116例(ESCC组)、体检健康者39例(对照组),收集两组空腹静脉血,离心留取血浆;选择ESCC组织及其配对的癌旁正常组织.采用实时荧光定量PCR法检测两组血浆和ESCC组织及癌旁正常组织lncRNA TUC338表达.随机选择46例ESCC患者,采用Spearman秩相关分析法分析血浆与肿瘤组织lncRNA TUC338表达的关系.分析血浆lncRNA TUC338表达与ESCC患者临床病理参数的关系.采用受试者工作特征(ROC)曲线评估血浆lncRNA TUC338表达诊断ESCC的价值.结果 ESCC组血浆lncRNA TUC338相对表达量明显高于对照组(P<0.01).ESCC组织lncRNA TUC338相对表达量明显高于癌旁正常组织(P<0.01).血浆与肿瘤组织lncRNA TUC338表达呈正相关关系(r=0.643,P<0.01).血浆lncRNA TUC338表达与ESCC患者 TNM分期及淋巴结转移有关(P均<0.05).ROC曲线分析显示,血浆lncRNA TUC338表达诊断ESCC的曲线下面积为0.684;其cut off值为1.415,此时其诊断ESCC的敏感性为63.4％,特异性为78.1％.结论 ESCC患者血浆lncRNA TUC338高表达,其表达变化与肿瘤TNM分期、淋巴结转移有关;血浆lncRNA TUC338有可能作为诊断ESCC的潜在生物标志物.

AimsThis study aimed to assess plasma lncRNA microRNA-31 hist gene (MIR31HG) as a novel diagnostic and therapeutic biomarker for esophageal squamous cell carcinoma (ESCC) and to investigate its role in ESCC.Main methodsThe expression of MIR31HG, Furin and MMP1 was examined via quantitative real-time polymerase chain reaction. MIR31HG expression between plasma and ESCC tissues was compared using Pearson correlation analysis; furthermore, the association between Furin/MMP1 levels and MIR31HG levels in ESCC tissues was analyzed. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic value of plasma MIR31HG. A WST-1 assay was performed to assess cell proliferation. The migratability and invasiveness of cells was determined via Transwell assays.Key findingsMIR31HG was significantly upregulated in ESCC tissues and plasma (P < 0.01). A significant positive association was obtained between plasma and tissue MIR31HG expression in ESCC (r = 0.78, P < 0.01). Furthermore, MIR31HG displayed high diagnostic sensitivity and specificity for predicting ESCC occurance. Furthermore, knockdown of MIR31HG suppressed the capacity for proliferation, migration, and invasion of ESCC cells (P < 0.01). In addition, silencing of MIR31HG inhibited the expression of Furin and MMP1 in EC9706 and EC1 and the level of Furin/MMP1 in ESCC tissues displayed a significant positive correlation with MIR31HG (P < 0.01).SignificanceMIR31HG can be used as a novel potential diagnostic biomarker and a potential therapeutic target for ESCC.

AIMS：: Recent research showed that Long non-protein coding RNA ferritin heavy chain 1 pseudogene 3 (FTH1P3) plays a crucial role in the course of tumor formation. The present study was aimed to explore its role in esophageal squamous cell carcinoma (ESCC). MAIN METHODS:Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was used to examine the expression levels of FTH1P3, mRNA SP1 and NF-kB in ESCC samples and cell lines. The impact of FTH1P3 knockdown was evaluated by WST-1 assays, colony formation assays, scratch wound assays, migration and invasion assays. KEY FINDINGS:FTH1P3 was significantly upregulated in ESCC tissues and cells (P < 0.001). Knockdown of FTH1P3 notably decreased the proliferation, migration, and invasion capacity of ESCC cells. Silencing of FTH1P3 decreased the expression of specificity protein 1 (Sp1) and NF-kB (p65) in EC9706 and EC1. SIGNIFICANCE:FTH1P3 plays a crucial role in ESCC tumorigenesis, and can be used as a potential therapeutic target for ESCC.

Esophageal squamous cell carcinoma (ESCC) is a common human malignancy with poor survival, which was usually diagnosed at an advanced stage. MicroRNAs (miRNAs), a class of single stranded noncoding RNAs with only 17–25 ribonucleotides, were demonstrated to play an important role in lots of cancers. In the recent years, increasing evidence revealed that circulating miRNAs exhibited great potential in the diagnosis of various types of cancers. The present study was designed to evaluate the diagnostic value of plasma miRNA-216a/b for ESCC. Our results showed that the expression level of plasma miRNA-216a/b was significantly lower in ESCC patients compared with that of healthy controls. The receiver operating characteristic (ROC) curve analysis yielded an area under the ROC curve (AUC) value of 0.877 [95% CI (confidence interval): 0.818–0.922] for miRNA-216a and 0.756 (95% CI: 0.685–0.819) for miRNA-216b. Clinical data indicated that plasma miRNA-216a/b were inversely correlated with lymph node metastasis and TNM stage. Additionally, the plasma miRNA-216b expression level was significantly upregulated in postoperative samples compared to preoperative samples. Our study, for the first time, demonstrated that plasma miRNA-216a/b might serve as potential biomarkers for the diagnosis of ESCC and dysregulation of miRNA-216a/b might be involved in the progression of ESCC.

BACKGROUND: Increasing evidence demonstrated that circulating miRNAs could serve as meaningfully non-invasive and reliable biomarkers for the detection of various cancers.OBJECTIVE: To investigate the expression level of plasma miRNA-718 in esophageal squamous cell carcinoma (ESCC) patients and its diagnostic value.METHODS: Quantitative real time polymerase chain reaction (qRT-PCR) method was performed to examine the expression levels of plasma miRNA-718 in 120 consecutive ESCC patients and 51 healthy controls. The difference of plasma miRNA-718 expression level between the paired pre- and postoperative patients was compared. The correlation between plasma miRNA-718 expression levels and clinicopathological characteristics was further analyzed and the receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic power of plasma miRNA-718 for ESCC.RESULTS: Plasma miRNA-718 expression level of ESCC patients was significantly lower than that of healthy controls. Compared with preoperative patients, the plasma miRNA-718 expression level of postoperative patients was significantly upregulated. Plasma miRNA-718 expression level was inversely correlated with the lymph node metastasis and TNM stage. The ROC curve analysis showed that plasma miRNA-718 yielded AUCs of 0.715, 0.689 and 0.620 for the detection of ESCC patients, early patients with Tis-T1 or early patients with TNM 0-I, respectively.CONCLUSION: Plasma miRNA-718 is downregulated in ESCC patients and might serve as a potential diagnostic marker for ESCC.