Abstract
Invasion and metastasis are major contributors to cancer-caused death in patients suffered from esophageal squamous cell carcinoma (ESCC). To explore the microRNAs involved in regulating invasion-metastasis cascade of ESCC, we established two pairs of sublines (30-U/D and 180-U/D) with distinct motility capacity from two ESCC cell lines (KYSE30 and KYSE180). Screening of the differentially expressed microRNAs identified that microRNA-92b-3p (miR-92b) could dramatically inhibit invasion and metastasis of ESCC cells in vitro and in vivo. Subsequent studies showed that miR-92b exerted its inhibitory function through suppressing the expression of integrin αV (ITGAV), which further reduced phosphrylated FAK and impaired Rac1 activation. Moreover, higher expression of miR-92b in ESCC tissues correlated inversely with lymph node metastasis and indicated better prognosis. Together, these results for the first time describe how miR-92b suppresses the motility of ESCC cells and provide a promise for diagnosis or therapy of ESCC invasion and metastasis.
Highlights
Esophageal carcinoma, including esophageal squa mous cell carcinoma (ESCC) and esophageal adeno carcinoma (EAC), ranks the sixth lethal cancer among males and the ninth deadly malignance among females around the world
Invasion and metastasis of ESCC cells are a complex process consisting of multiple events [4,5,6], among which directed migration of tumor cells is critical in most steps of invasion– metastasis cascade [7, 8]
MiR-92b expression was higher in 30-U cells than that of 30-D cells (Figure 1D), leading us to speculate that this microRNA could suppress motility and even invasionmetastasis cascade of ESCC cells
Summary
Esophageal carcinoma, including esophageal squa mous cell carcinoma (ESCC) and esophageal adeno carcinoma (EAC), ranks the sixth lethal cancer among males and the ninth deadly malignance among females around the world. Previous studies have shed a light on initiation and progression of ESCC [9,10,11], our understanding of directed motility of ESCC cells in invasion-metastasis cascade still remains poor. We explored how the directed migration of malignant cells is regulated in invasion and metastasis of ESCC. MiR10b decreased HOXD10 level to enhance metastasis and miR-335 inhibited SOX4 expression to suppress epithelial-mesenchymal transition (EMT) are examples of the first mode [14, 15]. We have previously found that miR-10b inhibited KLF4 expression, the protein which www.impactjournals.com/oncotarget maintained differentiation of esophageal epithelium and whose overexpression promoted inflammation-induced ESCC in mouse models [17, 18], to stimulate migration and invasion of ESCC cells [19]
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