Title:Oxidative Stress Upregulates PDCD4 Expression in Patients with Gastric Cancer via miR-21
Volume: 20
Issue: 11
Author(s): Honglei Tu, Haibing Sun, Yan Lin, Jie Ding, Kejun Nan, Zongfang Li, Qiang Shen and Yongchang Wei
Affiliation:
Keywords:
Gastric cancer, Oxidative stress, miR-21, programmed cell death 4.
Abstract: Reactive oxygen species (ROS) plays a key role in carcinogenesis by aberrantly inducing signaling networks that initiatiate
tumorigenesis and stimulate tumor progression. MicroRNAs (miRNAs) comprise a novel class of endogenous, small, noncoding RNAs
that negatively regulate approximately 30% of the genes in a cell via degradation or translational inhibition of their target mRNAs. However,
the effects of ROS on miRNAs expression and the role of miRNAs in ROS-mediated injury on carcinogenesis are uncertain. Using
UV spectrophotometry and enzyme-linked immunosorbent assay (ELISA), we examined tissues from human gastric cancers and tissues
adjascent to gastric cancer and normal gastric tissues and found that total anti-oxidation competence (T-AOC), superoxide dismutase
(SOD) and catalase (CAT) concentrations were lower in gastric cancer patients compared to the control subjects, while the concentrations
of DNA oxidative damage product 8-oxo-deoxyguanosine (8-OHdG) was higher. To determine the potential role of miRNA in gastric
carcinogenesis, real-time quantitative polymerase chain reaction (QPCR) analysis was performed. We found that human 8-oxoguanine
DNA N-glycosylase 1 (hOGG1) mRNA and miR-21 expression were significantly upregulated in gastric cancer tissues than in the adjacent
normal gastric tissues. Furthermore, the expression of programmed cell death 4 protein (PDCD4) in gastric cancer tissues was significantly
lower than in adjacent normal gastric tissues. The expression of miR-21 and PDCD4 was highly correlated with the degree of
differentiation, tumor staging, local lymphatic node metastasis and remote metastasis. Expression of miR-21 was negatively correlated
with T-AOC, SOD and CAT, but positively correlated with 8-OHdG and hOGG1mRNA. In addition, the relative expression of PDCD4
was negatively correlated with miR-21. These results suggest that the defensive balance of oxidation and antioxidant system in patients
with GC was impaired, resulting in enhanced oxidative tissue injury, which may directly contribute to gastric carcinogenesis. Thus we
conclude that ROS promotes gastric carcinogenesis via upregulating miR-21 expression which in turn down-regulates the expression of
PDCD4 in gastric cancer cells.