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Silencing PRSS1 suppresses the growth and proliferation of gastric carcinoma cells via the ERK pathway
Authors:Dongmei Ye  Yuxuan Li  Heliang Zhang  Zhiwei Zhou  Yujie Tang  Peng Wu  Qiang Zhao  Zhiwei Zhang
Abstract:Background: Gastric carcinoma (GC) is one of the most common malignant tumors and seriously threatens human life and health.Methods: In the present study, 243 differentially expressed proteins in GC were identified using laser capture microdissection (LCM) combined with isotopically labeled quantitative proteomics technology. The expression of serine protease 1 (PRSS1) protein was analyzed by immunohistochemistry and Western blot. MTT and colony formation assays were employed to determine the effect of PRSS1 expression on the growth and proliferation of GC cells. Then, we observed the expression of miR-146a-5p in GC by qRT-PCR. A dual luciferase assay was performed to determine whether PRSS1 is a target gene of miR-146a-5p. We also explored the influence of miR-146a-5p expression on PRSS1 expression and on the growth and proliferation of GC cells. Finally, Western blotting was used to analyze the effect of PRSS1 expression on the activation of the ERK signaling pathway.Results: We confirmed that PRSS1 expression was significantly increased and was positively correlated with the differentiation, tumor size and lymph node metastasis of GC. Subsequently, we found that overexpression of PRSS1 promoted the growth and proliferation of cells, whereas silencing PRSS1 expression inhibited the growth and proliferation of MGC803 cells by inhibiting activation of the ERK signaling pathway via reductions in PAR-2 activation. MiR-146a-5p targets PRSS1 and suppresses the growth and proliferation of MGC803 cells.Conclusions: miR-146a-5p targets PRSS1 and suppresses the growth and proliferation of MGC803 cells. Silencing PRSS1 expression inhibits the ERK signaling pathway by reducing PAR-2 activation, resulting in suppressed growth and proliferation of MGC803 GC cells.
Keywords:gastric carcinoma   proteomics   PRSS1   miR-146a-5p   ERK   PAR-2
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