Int J Biol Sci 2021; 17(4):957-971. doi:10.7150/ijbs.52591 This issue

Research Paper

Silencing PRSS1 suppresses the growth and proliferation of gastric carcinoma cells via the ERK pathway

Dongmei Ye1,3*, Yuxuan Li1*, Heliang Zhang1, Zhiwei Zhou4, Yujie Tang4, Peng Wu5, Qiang Zhao2✉, Zhiwei Zhang1✉

1. Cancer Research Institute of Hengyang Medical College, University of South China; Key Laboratory of Cancer Cellular and Molecular Pathology in Hunan Province, Hunan Hengyang 421001, China.
2. Department of Pathology, The First Affiliated Hospital of University of South China, Hunan Hengyang 421001, Hunan Province China.
3. Department of Pathology, Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province 330008, China.
4. Clinical Medicine of Hengyang Medical College, University of South China, Hengyang 421001, Hunan Province, China.
5. Department of Critical Care Medicine, Hengyang Maternal and Child Health Hospital, Hengyang, 421001, Hunan Province, China.
*These authors contributed equally to this work.

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Citation:
Ye D, Li Y, Zhang H, Zhou Z, Tang Y, Wu P, Zhao Q, Zhang Z. Silencing PRSS1 suppresses the growth and proliferation of gastric carcinoma cells via the ERK pathway. Int J Biol Sci 2021; 17(4):957-971. doi:10.7150/ijbs.52591. Available from https://www.ijbs.com/v17p0957.htm

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Abstract

Graphic 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