MiR-142-3p as a potential prognostic biomarker for esophageal squamous cell carcinoma.

microRNAs (miRNAs), small non-coding RNAs, are always aberrantly expressed in many diseases including human cancers. The aim of this study was to examine and determine the clinical significance of hsa-miR-31, hsa-miR-142-3p, hsa-miR-338-3p, and hsa-miR-1261 expression in esophageal squamous cell carcinoma (ESCC). Expression levels of four selected miRNAs, initially evaluated by microarray, were validated by qRT-PCR. Various statistical methods were used to analyze the relationship between miRNA expression and clinicopathologic features and prognosis in 91 patients with ESCC. MiR-31 and miR-142-3p expression were correlated to histological differentiation in ESCC (P < 0.05, Student's t-test); high miR-142-3p expression was associated with a poor prognosis in all 91 ESCC patients (P = 0.014, log-rank) and identified as an independent prognostic factor in ESCC (P = 0.017, univariate Cox; P = 0.022, multivariate Cox). More importantly, stratified analysis indicated that high miR-142-3p expression was correlated to a poor prognosis within good-prognosis groups comprised of ESCC patients with small tumor size, negative lymph node metastasis, or early stage (all P < 0.05). The main findings suggest that miR-142-3p is involved in the progression of ESCC and is a potential prognostic biomarker for ESCC.

Lin RJ ，Xiao DW ，Liao LD ，Chen T ，Xie ZF ，Huang WZ ，Wang WS ，Jiang TF ，Wu BL ，Li EM ，Xu LY ... -  《-》

Expression of lysyl oxidase is correlated with lymph node metastasis and poor prognosis in esophageal squamous cell carcinoma.

Sakai M ，Kato H ，Sano A ，Tanaka N ，Inose T ，Kimura H ，Sohda M ，Nakajima M ，Kuwano H ... -  《-》

Differential expression profiles of microRNAs as potential biomarkers for the early diagnosis of esophageal squamous cell carcinoma.

Yang M ，Liu R ，Sheng J ，Liao J ，Wang Y ，Pan E ，Guo W ，Pu Y ，Yin L ... -  《-》

Downregulation of miR-138 sustains NF-κB activation and promotes lipid raft formation in esophageal squamous cell carcinoma.

Constitutive activation of NF-κB signaling plays vital roles in esophageal squamous cell carcinoma (ESCC) progression. The aim of this study was to evaluate the effect of miR-138 on NF-κB activation and ESCC progression. Expression of miR-138 in ESCC cell lines, ESCC tissues, and 205 archived ESSC specimens was determined using real-time PCR analysis. Anchorage-independent growth, chicken chorioallantoic membrane, Transwell matrix invasion and Annexin V-binding assays, and a xenograft tumor model were used to determine the role of miR-138 in ESCC progression. The effect of miR-138 on NF-κB activation was investigated using IKK in vitro kinase, electrophoretic mobility shift, lipid raft isolation, and luciferase reporter assays. miR-138 was downregulated and inversely correlated with tumor progression and patient survival in ESCCs. Downregulation of miR-138 enhanced, whereas upregulation of miR-138 reduced, the aggressive phenotype of ESCC cells both in vitro and in vivo. Silencing miR-138 promoted K63-linked polyubiquitination of the NF-κB signaling intermediaries TRAF2 and RIP1 and sustained NF-κB activation. Furthermore, downregulation of miR-138 induced lipid raft formation via upregulating multiple components of lipid rafts, including FLOT1, FLOT2, and caveolin-1. Importantly, the in vitro analysis was consistent with a significant inverse correlation between miR-138 expression and NF-κB hyperactivation in a cohort of human ESCC specimens. Our results show that miR-138 functions as a tumor-suppressive miRNA and that downregulation of miR-138 contributes to constitutive NF-κB activation and ESCC progression.

Gong H ，Song L ，Lin C ，Liu A ，Lin X ，Wu J ，Li M ，Li J ... -  《-》

Prognostic value of microRNA-100 in esophageal squamous cell carcinoma.

MicroRNA-100 (miR-100) has been demonstrated to be implicated in tumorigenesis and tumor progression of human esophageal squamous cell carcinoma (ESCC). However, its expression patterns in ESCC are controversial and its prognostic value in this malignancy has not been fully elucidated. The aim of this study was to investigate the expression and clinical significance of miR-100 in ESCC. Real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) was performed to detect expression levels of miR-100 in 120 self-paired specimens of ESCC and adjacent normal esophageal tissues. The associations of miR-100 expression with clinicopathologic features, locoregional progression-free survival (LPFS), distant progression-free survival (DPFS), and overall survival (OS) of patients with ESCC were statistically analyzed. Compared with adjacent normal esophageal tissues, the expression levels of miR-100 in ESCC were significantly decreased (normal versus ESCC: 3.53 ± 1.22 versus 1.89 ± 0.38, P <0.001). Additionally, low miR-100 expression in ESCC tissues was significantly associated with the advanced clinical stage (P = 0.008), the presence of distant metastasis (P = 0.008), and the great depth of invasion (P = 0.02). Moreover, univariate analysis revealed that low miR-100 expression was associated with poor LPFS, DPFS, and OS. In multivariate analysis, miR-100 expression was identified as an independent prognostic factor for all LPFS, DPFS, and OS. These findings show the reduced expression of miR-100 in human ESCC tissues and suggest a crucial role of its downregulation in ESCC progression and prognosis. More interestingly, the detection of miR-100 expression may be used to efficiently screen those ESCC patients who would benefit from radiotherapy.

Zhou S ，Yang B ，Zhao Y ，Xu S ，Zhang H ，Li Z ... -  《-》