PLCε1: a potential target of RNA interference therapy for gastric cancer.

Abstract

Phospholipase C epsilon 1 (PLCε1) has been recently identified as a novel potential biomarker for gastric cancer because of its critical role in inflammation and tumorigenesis. Until now, there are no further reports to investigate the feasibility of gene therapy by suppressing PLCε1 expression for gastric cancer. In this study, a small interfering RNA (shRNA) targeting PLCε1 was firstly transfected into gastric cancer cells in order to silence PLCε1 expression. Both mRNA and protein expression of PLCε1 in gastric cancer cells significantly reduced by RT-PCR and Western blotting analysis. Moreover, subsequent results revealed that PLCε1 shRNA depressed the in vitro and in vivo growth of gastric cancer cells by using MTT assay and tumor xenograft experiment. Furthermore, after PLCε1 shRNA transfection, the expression of proinflammatory molecules including tumor necrosis factor-α (TNF-α), cyclooxygenase 2 (COX-2), interleukin (IL)-6 and chemokine (C-X-C motif) ligand (CXCL)-1 were unaffected, but only chemokine (C-C motif) ligand (CCL)-2 expression decreased in the gastric cancer cells. It is implied that PLCε1 may inhibit the growth of gastric cancer cells via CCL-2 protein mediated pathway. These results suggest that PLCε1 might be an alternative molecular target for gastric cancer gene therapy.

• Authors: Fang Yan, Qiang Fu
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 448 Issue 4 Pg. 409-13 (Jun 13 2014) ISSN: 1090-2104 [Electronic] United States
• PMID: 24796667 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• Biomarkers, Tumor
• CCL2 protein, human
• Chemokine CCL2
• RNA, Messenger
• RNA, Neoplasm
• Phosphoinositide Phospholipase C
• phospholipase C epsilon

Topics

• Animals
• Biomarkers, Tumor (antagonists & inhibitors, genetics)
• Cell Line, Tumor
• Cell Proliferation
• Chemokine CCL2 (genetics, metabolism)
• Down-Regulation
• Female
• Gene Knockdown Techniques
• Genetic Therapy (methods)
• Humans
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Phosphoinositide Phospholipase C (antagonists & inhibitors, genetics)
• RNA Interference
• RNA, Messenger (genetics, metabolism)
• RNA, Neoplasm (genetics, metabolism)
• Signal Transduction
• Stomach Neoplasms (enzymology, genetics, therapy)
• Xenograft Model Antitumor Assays