PRDX4 overexpression is associated with poor prognosis in gastric cancer.

Oncology letters (2020-04-10)
Sun Yi Park, Young-Joon Lee, Jiho Park, Tae-Han Kim, Soon-Chan Hong, Eun-Jung Jung, Young-Tae Ju, Chi-Young Jeong, Hee Jin Park, Gyung Hyuck Ko, Dae Hyun Song, Miyeong Park, Jiyun Yoo, Sang-Ho Jeong
ABSTRAKT

Peroxiredoxin IV (PRDX4) is a multifunctional protein that is involved in cell protection against oxidative injury, regulation of cell proliferation, modulation of intracellular signaling, and the pathogenesis of tumors. We previously conducted a proteomic analysis to investigate tumor-specific protein expression in gastric cancer. The aim of the present study was to investigate whether PRDX4 could be a marker of poor prognosis in patients with gastric cancer. Immunohistochemistry was used to validate PRDX4 as a prognostic marker for gastric cancer. Short hairpin RNA (shRNA)-mediated knockdown of PRDX4 expression in AGS cells and MKN28 cells was used for functional studies, and PRDX4 overexpression in PRDX4-depleted cells was used for knock-in studies. Based on immunohistochemistry data, TNM stage and PRDX4 were independent prognostic factors in the Cox proportional hazard model (P<0.05). In the survival analysis, the PRDX4-overexpressing group demonstrated significantly worse survival than the PRDX4-underexpression group (P<0.01). In vitro, knockdown of PRDX4 expression by shRNA caused a significant decrease in cancer invasion. Conversely, overexpression of PRDX4 in PRDX4-depleted cancer cells promoted migration and invasion. By measuring the expression of EMT-related genes, we found that E-cadherin was increased in shPRDX4 cells compared with control shMKN28 cells, and snail and slug were decreased in shPRDX4-1 cells compared with sh-control cells. Furthermore, the expression levels of these genes could be recovered in rescue experiments. In conclusion, the results of the present study suggested that PRDX4 is a marker of poor prognosis in gastric cancer and that PRDX4 is associated with cancer cell migration and invasion via EMT.

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Sigma-Aldrich
Puromycin dihydrochloride, Ready Made Solution, from Streptomyces alboniger, 10 mg/mL in H2O
Sigma-Aldrich
MISSION® pLKO.1-puro Empty Vector Control Plasmid DNA, Contains no shRNA insert
Sigma-Aldrich
MISSION® esiRNA, targeting human PRDX4