High‐level expression of PRSS3 correlates with metastasis and poor prognosis in patients with gastric cancer

Abstract

Background and Objectives Serine protease‐3 (PRSS3) is a known contributor to the genesis and development of malignant tumors, although its role in gastric cancer (GC) is still unclear. Methods PRSS3 expression in GC tissue samples and its relationship with clinicopathological features were analyzed. Effects of GC cellular responses to the introduction of small interfering RNA (siRNA)‐mediated and short hairpin RNA (shRNA)‐mediated interference with tumor PRSS3 expression were also assessed. Results PRSS3 was significantly upregulated in GC tissues, and PRSS3 protein levels were higher in tumors that developed metastases soon after the surgery compared with those that remained metastasis‐free. High expression of PRSS3 was associated with tumor N staging and independently predictive of postoperative prognosis in patients with GC. The V1 variant of PRSS3 was primarily detected in GC tissue and cell lines, the others (V2‐V4) being scarcely detectable. Methylation and demethylation drugs had no impact on expression levels of any PRSS3 transcriptional variant. The downregulated PRSS3 expression suppressed GC cell growth, migration, and invasion in vitro and in vivo. Conclusions PRSS3 appears to act as an oncogene of GC. High PRSS3 expression portends postoperative metastasis, serving as an effective biomarker of poor therapeutic outcomes.

High Expression of PRSS3 Indicates Unfavorable Clinical Outcomes in Colon Adenocarcinoma

“…It has been widely acknowledged that proteases were aberrantly expressed in several types of cancer cells, which played important roles in metastatic progression. 19 Proteolytic enzymes can degrade cell adhesion molecules and promote epithelial-mesenchymal transition, thus supporting tumor cell motility. 20 In addition, it was reported that proteases can enhance tumor cell invasion through reconstructing the extracellular matrix and they are also essential for metastatic colony formation.…”

Increased expression of hematological and neurological expressed 1 (HN1) is associated with a poor prognosis of hepatocellular carcinoma and its knockdown inhibits cell growth and migration partly by down‐regulation of c‐Met

“…RNA interference was according to the previous procedure with modifications . After seeded into 96 or six‐well plates for overnight, cells were transfected with HN1‐siRNA, c‐Met‐siRNA, or NC‐siRNA (final concentration 50 nM) using lipofectamine 2000 (Invitrogen, Carlsbad, CA, USA) according to the manufacturer's instructions.…”

“…11,12 2.5 | Cell culture RNA interference was according to the previous procedure with modifications. 13 β-actin was used as an internal control to normalize gene expression, the relative quantification was determined by 2ΔCt method.…”

Exome Sequencing Reveals Genetic Variability and Identifies Chronic Prognostic Loci in Chinese Sarcoidosis Patients

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