Expression and prognostic impact of PRL-3 in lymph node metastasis of gastric cancer: its molecular mechanism was investigated using artificial microRNA interference.
High PRL-3 expression had been reported to have close association with lymph node metastasis (LNM) of gastric cancer. However, the prognostic significance of highly expressing PRL-3 in LNM of human gastric cancer and the role in the metastasis remain unclear. Our study examined PRL-3 expression both in the LNM (n = 107) and in the primary lesion (n = 137) of gastric cancer, and compared the overall survival rates. RNA interference, induced by recombinant plasmid pcDNA.rPRL3-miR expressing artificial PRL-3 miRNA, was employed to knockdown PRL-3 expression in human SGC7901 gastric cancer cells. Invasion assay and migration assay in vitro were conducted to determine the role of PRL-3 in the metastasis. The role of PRL-3 in the proliferation of SGC7901 cells and tumor growth were also determined. We observed that high PRL-3 expression was more frequently detected in the LNM than in the matched primary lesion (72.9 vs. 47.7%, p < 0.001). Furthermore, the overall survival rate of the patients with high expression of PRL-3 in the LNM was significantly less than those with moderate/low expression (p = 0.003). Importantly, knockdown of PRL-3 can significantly reduce both invasion and migration potencies of SGC7901 cells (p < 0.001), and significantly suppressed the proliferation of SGC7901 cells and slowed down the tumor growth (p < 0.001). It was concluded that high expression of PRL-3 in the LNM had a negative impact on the prognosis of the patients, and plays important roles in LNM of gastric cancer and the tumor growth, which can be a potential therapeutic target and a prognostic factor.
Department of Gastroenterology Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Gastric Cancer Centre, Sun Yat-Sen University, Guangzhou, China.
Zhao
Z
Wang
Yu-Long
YL
He
Shi-Rong
SR
Cai
Wen-Hua
WH
Zhan
Zeng-Rong
ZR
Li
Bao-He
BH
Zhu
Chuang-Qi
CQ
Chen
Jin-Ping
JP
Ma
Zheng-Xuan
ZX
Chen
Wen
W
Li
Long-Juan
LJ
Zhang
D000230:Adenocarcinoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D015153:Blotting, Western; D045744:Cell Line, Tumor; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis / Q000235:genetics / Q000473:pathology*; D008297:Male; D035683:MicroRNAs; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D011379:Prognosis; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis* / Q000235:genetics; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D014162:Transfection
D014408:Biomarkers, Tumor; D035683:MicroRNAs; D009363:Neoplasm Proteins; C484730:PTP4A3 protein, human; D017027:Protein Tyrosine Phosphatases