MiR-150 is associated with poor prognosis in esophageal squamous cell carcinoma via targeting the EMT inducer ZEB1.

The association of microRNAs (miRs) with cancer progression has been established in many cancers including esophageal squamous cell carcinoma (ESCC). A public microarray database showed that the expression of miR-150 was lower in ESCC than in normal esophageal mucosa. Here, we focused on ZEB1, epithelial-mesenchymal-transition (EMT)-inducer, as a target gene of miR-150 based on in silico predictions. The purpose of this study was to clarify the clinicopathological significance of miR-150 in ESCC, and to investigate miR-150's EMT-regulatory ability. Quantitative RT-PCR was used to evaluate miR-150 expression in 108 curative resected ESCC samples to determine the clinicopathological significance. Moreover, we examined the in vitro and in vivo function of miR-150 via degradation of ZEB1. MiR-150 expression was significantly lower in cancer tissues compared to adjacent non-cancerous tissues (P < 0.001). Low expression of miR-150 in ESCC contributed to malignant potential, such as tumor depth, lymph node metastasis, lymphatic invasion, venous invasion, clinical staging, and poor prognosis (P < 0.05). In vitro assays showed that EMT-inducer-ZEB1 is a new direct target of miR-150. Moreover, miR-150 induced MET-like changes in TE-8 cells through ZEB1 degradation (e.g., E-cadherin expression, vimentin repression, epithelial morphology, and suppression of migration ability), and significantly inhibited tumorigenicity and tumor growth in a mouse xenograft model. Analysis of the regulation of ZEB1 by miR-150 could provide new insights into preventing metastasis and also suggests novel targeted therapeutic strategies in ESCC.

Yokobori T ，Suzuki S ，Tanaka N ，Inose T ，Sohda M ，Sano A ，Sakai M ，Nakajima M ，Miyazaki T ，Kato H ，Kuwano H ... -  《-》

Loss of miR-200b promotes invasion via activating the Kindlin-2/integrin β1/AKT pathway in esophageal squamous cell carcinoma: An E-cadherin-independent mechanism.

Zhang HF ，Alshareef A ，Wu C ，Li S ，Jiao JW ，Cao HH ，Lai R ，Xu LY ，Li EM ... -  《Oncotarget》

Overexpression of zinc finger E-box binding homeobox factor 1 promotes tumor invasiveness and confers unfavorable prognosis in esophageal squamous cell carcinoma.

Yang X ，Wang Q ，Dai W ，Zhang J ，Chen X ... -  《-》

Tumor suppressor miR-128-3p inhibits metastasis and epithelial-mesenchymal transition by targeting ZEB1 in esophageal squamous-cell cancer.

MicroRNAs (miRNAs) are some short RNAs that regulate multiple biological functions at post-transcriptional levels, such as tumorigenic processes, inflammatory lesions and cell apoptosis. Zinc finger E-box binding homeobox factor 1 (ZEB1) is a crucial mediator of epithelial-mesenchymal transition (EMT). It induces malignant progression of various cancers including human esophageal squamous-cell carcinoma (ESCC). In this study, we found that miR-128-3p was downregulated in ESCC tissues and cells by using PCR. Moreover, down-regulated expression of miR-128-3p was testified to be associated with poor prognosis of ESCC patients and might be regarded as an independent prognostic factor. Then, we examined the role of miR-128-3p in ESCC cells, and found that miR-128-3p could suppress the cell migration and invasion in vitro. Furthermore, ZEB1 was confirmed to be a direct target of miR-128-3p by luciferase reporter assay. Rescue experiments proved that EMT was regulated by miR-128-3p via suppression of ZEB1. Taken all together, we conclude that miR-128-3p suppresses EMT and metastasis via ZEB1, and miR-128-3p may be a critical mediator in ESCC.

Zhao L ，Li R ，Xu S ，Li Y ，Zhao P ，Dong W ，Liu Z ，Zhao Q ，Tan B ... -  《-》

Long Non-coding RNA X-Inactive Specific Transcript Promotes Esophageal Squamous Cell Carcinoma Progression via the MicroRNA 34a/Zinc Finger E-box-Binding Homeobox 1 Pathway.

The long non-coding RNA X-inactive specific transcript (XIST) plays a crucial role in transcriptional silencing of the X chromosome. Zinc finger E-box-binding homeobox 1 (ZEB1) is a transcription factor involved in epithelial-mesenchymal transition (EMT) regulation. This study aimed to investigate the impact of XIST on esophageal squamous cell carcinoma (ESCC) progression and its underlying mechanism involving the miR-34a/ZEB1/E-cadherin/EMT pathway. XIST and ZEB1 expression were analyzed using quantitative PCR and immunohistochemistry. XIST knockdown was achieved in KYSE150 ESCC cells using siRNA or shRNA lentivirus transfection. Proliferation, migration, and invasion abilities were assessed, and luciferase reporter assays were performed to confirm XIST-miR-34a-ZEB1 interactions. In vivo ESCC growth was evaluated using a xenograft mouse model. XIST and ZEB1 were upregulated in tumor tissues, correlating with metastasis and reduced survival. XIST knockdown inhibited proliferation, migration, and invasion of KYSE150 cells. It decreased ZEB1 expression, increased E-cadherin and miR-34a levels. Luciferase reporter assays confirmed miR-34a binding to XIST and ZEB1. XIST knockdown suppressed xenograft tumor growth. XIST promotes ESCC progression via the miR-34a/ZEB1/E-cadherin/EMT pathway. Targeting the XIST/miR-34a/ZEB1 axis holds therapeutic potential and serves as a prognostic biomarker in ESCC.

Guo B ，He M ，Ma M ，Tian Z ，Jin J ，Tian G ... -  《-》