miR-106b promotes cell invasion and metastasis via PTEN mediated EMT in ESCC

Abstract

Abstract. MicroRNA (miR)-106b serves an essential function in a variety of human cancer types, particularly in the process of invasion and metastasis. However, the function and mechanism of miR-106b in the invasion and metastasis of esophageal squamous cell carcinoma (ESCC) has remained elusive. In the present study, it was demonstrated that miR-106b was upregulated in ESCC tissues and cell lines. Furthermore, miR-106b expression in ESCC tissues was positively associated with lymphatic metastasis. Inhibition of miR-106b in EC-1 and EC9706 cells decreased not only the invasion and metastasis ability but also the proliferation ability of EC-1 and EC9706 cells. In addition, miR-106b had the ability to induce epithelial-to-mesenchymal transition (EMT) in EC-1 and EC9706 cells. In terms of the underlying mechanism, it was revealed that miR-106b promoted the invasion, metastasis and proliferation ability of EC-1 and EC9706 cells by directly targeting phosphatase and tension homolog (PTEN). Furthermore, miR-106b induced EMT in EC-1 and EC9706 cells by suppressing the expression of PTEN. In summary, the present study revealed that miR-106b contributed to invasion and metastasis in ESCC by regulating PTEN mediated EMT. Downregulation of miR-106b may be a novel strategy for preventing tumor invasion and metastasis. IntroductionEsophageal squamous cell carcinoma (ESCC) is the most malignant lesion in China, particularly in Linzhou, Henan (1).Treatment of ESCC is largely useless due to the occurrence of invasion and metastasis in the early stage. However, the mechanism of invasion and metastasis of ESCC has been poorly elucidated (2).Epithelial-to-mesenchymal transition (EMT) now is always viewed as a key event that occurs during cancer invasion and metastasis. However, current understanding of the alterations that give rise to the occurrence of EMT is limited. MicroRNAs (miRNA/miRs) are small non-coding RNA molecules that may directly regulate target gene expression by binding to their 3'-untranslated regions (3'-UTRs) (3,4). Furthermore, miRNAs have been demonstrated to serve notable functions in tumor invasion and metastasis by functioning as EMT suppressors or inducers (5,6). miR-106b is a type of miRNA transcribed from the miR-106b-25 cluster located on chromosome 7 (7). Yau et al (8) reported that miR-106b overexpressed in hepatocellular carcinoma cells and that the overexpression of miR-106b may promote cell migration and metastasis by activating the EMT process. Zhou et al (9) additionally demonstrated that miR-106b contributed as an EMT inducer in breast cancer. However, whether miR-106b participates in the invasion and metastasis process of ESCC by inducing EMT and the mechanism of how miR-106b induces EMT in ESCC had not been fully explored until now. miRNAs participate in the occurrence and development of a cancer by regulating the post-transcriptional process of their target gene. Several genes have been verified to be the targets of miR-106b, including transforming growth factor-β type II receptor, cyclin de...

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