Expression of the transmembrane-4-L-six-family-1 (TM4SF1) is high in human pancreatic cancer cells, but the underlying mechanism remains unclear. In this study, we aimed to identify and characterize microRNAs that regulate TM4SF1 expression in PC cells. Western blot analysis and quantitative polymerase chain reaction were used to detect TM4SF1 and hsa-miR-141 levels in four PC cell lines. SW1990 and BxPc-3 cells were transfected with the inhibitor miR-141, the inhibitor negative control, the miR-141 mimic and the mimic negative control; and cell invasion, migration, proliferation, cell cycle progression and apoptosis were detected by Transwell, MTT and flow cytometry assays, respectively. The miR-141 levels negatively correlated with the TM4SF1 protein levels in PC cells. The TM4SF1 protein levels were lower in the 141M group but higher in the 141I group, although the TM4SF1 mRNA levels had no significant changes, compared to the negative controls. Luciferase assays demonstrated that hsa-miR-141 directly targeted the 3'-untranslated region of the TM4SF1 gene. In addition, miR-141 downregulated TM4SF1 expression to inhibit invasion and migration of PC cells but had no effects on cell proliferation, cell cycle progression or apoptosis. TM4SF1 is a direct target of miR-141. Our findings that TM4SF1 expression was inhibited by miR-141 provide new insights into the oncogenic mechanism of TM4SF1 and suggest that miR-141 represents a novel molecular target for PC therapy.
MicroRNAs have emerged as crucial regulators of tumorigenesis. However, the mechanism by which miR‑203 is involved in the pathogenesis of pancreatic cancer (PC) remains elusive. In the present study, PC cell lines were used as an experimental model to investigate the expression and functional role of miR‑203 in PC. miR‑203 mimic virus, miRNA negative control virus and Survivin shRNA virus were transfected into the PC cell line, CFPAC‑1. mRNA and protein levels of Survivin were detected using qPCR and western blot analysis. Proliferation, apoptosis and cell cycle profiles were detected by an MTT assay and flow cytometry. Female BALB/cA‑nu nude mice were used to validate the role of miR‑203 in vivo. The protein levels of Survivin were found to negatively correlate with miR‑203 levels in four PC cell lines. A luciferase assay revealed that Survivin was a direct target of miR‑203. Transfection with miR‑203 mimic inhibited CFPAC‑1 cell proliferation and induced apoptosis and G1 phase cell cycle arrest, similar to knockdown of Survivin. In the in vivo nude mouse model, the downregulation of Survivin by knockdown of Survivin or transfection with miR‑203 mimic inhibited tumor growth. Results of the current study indicate that miR‑203 regulates the proliferation, apoptosis and cell cycle progression of PC cells by targeting Survivin.
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