SQLE induces epithelial-to-mesenchymal transition by regulating of miR-133b in esophageal squamous cell carcinoma.

Increasing evidence suggests that microRNAs, which control gene expression at the post-transcriptional level, are aberrantly expressed in cancers and play significant roles in carcinogenesis and cancer progression. In this study, we show differential miR-133b down-expression in human esophageal squamous cell carcinoma (ESCC) cells and tissues. In addition, squalene epoxidase (SQLE), a key enzyme of cholesterol synthesis, is identified as the direct downstream target gene of miR-133b by luciferase gene reporter assay. Furthermore, ectogenic miR-133b expression and SQLE knockdown can inhibit proliferation, invasion, and metastasis, and diminish epithelial-to-mesenchymal transition (EMT) traits of ESCC in vitro, implying that miR-133b-dependent SQLE can induce tumorigenicity and that SQLE is an EMT inducer. Xenograft experiment results also proved the biological function of SQLE in vivo. Therefore, we conclude that miR-133b-dependent SQLE plays a critical role in the potential metastasis mechanisms in ESCC.

Qin Y ，Zhang Y ，Tang Q ，Jin L ，Chen Y ... -  《-》

MiR-375 suppresses invasion and metastasis by direct targeting of SHOX2 in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is the most common histological type in China. MicroRNAs are endogenously expressed in mammals and play a significant role in tumor invasion and metastasis by targeting potential downstream genes. In the present study, microarray analysis showed that miR-375 expression was distinctly downregulated in ESCC compared with that in normal esophageal epithelium tissues. Then, luciferase reporter assay showed that SHOX2 was the direct downstream target of miR-375 and this interaction was confirmed by the rescue experiments. Quantitative polymerase chain reaction results also showed that SHOX2 expression was upregulated in ESCC cells and tissues. Further analysis showed that SHOX2 induced proliferation, invasion, and metastasis of ESCC both in vivo and in vitro. Moreover, the interaction between miR-375 and SHOX2 affected the epithelial-to-mesenchymal transition. We conclude that miR-375 may suppress invasion and metastasis of ESCC by directly targeting SHOX2. The miR-375/SHOX2 axis may be a novel therapeutic target for ESCC.

Yi J ，Jin L ，Chen J ，Feng B ，He Z ，Chen L ，Song H ... -  《-》

miR-145, miR-133a and miR-133b: Tumor-suppressive miRNAs target FSCN1 in esophageal squamous cell carcinoma.

MicroRNAs (miRNAs), noncoding RNAs 21-25 nucleotides in length, regulate gene expression primarily at the posttranscriptional level. Growing evidence suggests that miRNAs are aberrantly expressed in many human cancers, and that they play significant roles in carcinogenesis and cancer progression. A search for miRNAs with a tumor-suppressive function in esophageal squamous cell carcinoma (ESCC) was performed using the miRNA expression signatures obtained from ESCC clinical specimens. A subset of 15 miRNAs was significantly downregulated in ESCC. A comparison of miRNA signatures from ESCC and our previous report identified 4 miRNAs that are downregulated in common (miR-145, miR-30a-3p, miR-133a and miR-133b), suggesting that these miRNAs are candidate tumor suppressors. Gain-of-function analysis revealed that 3 transfectants (miR-145, miR-133a and miR-133b) inhibit cell proliferation and cell invasion in ESCC cells. These miRNAs (miR-145, miR-133a and miR-133b), which have conserved sequences in the 3'UTR of FSCN1 (actin-binding protein, Fascin homolog 1), inhibited FSCN1 expression. The signal from a luciferase reporter assay was significantly decreased at 2 miR-145 target sites and 1 miR-133a/b site, suggesting both miRNAs directly regulate FSCN1. An FSCN1 loss-of-function assay found significant cell growth and invasion inhibition, implying an FSCN1 is associated with ESCC carcinogenesis. The identification of tumor-suppressive miRNAs, miR-145, miR-133a and miR-133b, directly control oncogenic FSCN1 gene. These signal pathways of ESCC could provide new insights into potential mechanisms of ESCC carcinogenesis.

Kano M ，Seki N ，Kikkawa N ，Fujimura L ，Hoshino I ，Akutsu Y ，Chiyomaru T ，Enokida H ，Nakagawa M ，Matsubara H ... -  《-》

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 ... -  《-》

MicroRNA-145 Inhibits Cell Migration and Invasion and Regulates Epithelial-Mesenchymal Transition (EMT) by Targeting Connective Tissue Growth Factor (CTGF) in Esophageal Squamous Cell Carcinoma.

Han Q ，Zhang HY ，Zhong BL ，Wang XJ ，Zhang B ，Chen H ... -  《MEDICAL SCIENCE MONITOR》