In conclusion, we identify miR-146a as a potential tumor suppressor in patients with EOC. miR-146a downregulates the expression of SOD2 and enhances ROS generation, leading to increased apoptosis, inhibition of proliferation, and enhanced sensitivity to chemotherapy.
In conclusion, we identify miR-146a as a potential tumor suppressor in patients with EOC. miR-146a downregulates the expression of SOD2 and enhances ROS generation, leading to increased apoptosis, inhibition of proliferation, and enhanced sensitivity to chemotherapy.
However, higher levels of tumor MDA, Mn-SOD protein expression and urinary 8-epi-PGF2α were observed along with lower tumor CAT activity in poorly differentiated or undifferentiated (grade 3, G 3) versus well or moderately well differentiated (grade 1-2, G 1-2) serous EOC tumors.
Expression of manganese superoxide dismutase (SOD2), which regulates cellular ROS, is markedly down-regulated in CRPC when compared with hormone-responsive tumors.
These results suggest that overexpression of MnSOD gene is involved in the suppression of spontaneous apoptosis, without a resultant alteration in the tumor growth.
In direct support of these findings, the tumor promoting effects of Cav-1 deficient fibroblasts could be functionally suppressed (nearly 2-fold) by the recombinant over-expression of SOD2 (superoxide dismutase 2), a known mitochondrial enzyme that de-activates superoxide, thereby reducing mitochondrial oxidative stress.
The Oncomine database confirmed higher MnSOD mRNA expression in ccRCC than in normal tissues, and immunohistochemistry analysis revealed that MnSOD protein expression was inversely associated with pathologic grade, clinical stage, tumor size, M status, and cancer-specific survival.
In the present study, we report that constitutive TrkAIII expression in human SH-SY5Y NB cells inhibits Rotenone, Paraquat and LY83583-induced mitochondrial free radical reactive oxygen species (ROS)-mediated death by stimulating SOD2 expression, increasing mitochondrial SOD2 activity and attenuating mitochondrial free radical ROS production, in association with increased mitochondrial capacity to produce H2O2, within the context of a more tumour stem cell-like phenotype.
In recent studies, decreased expression of Mn SOD, an intramitochondrial enzyme responsible for the dismutation of anion superoxide, has been reported in multiple, malignant cell types, whereas its gene has been proposed as a tumour suppressor gene in melanoma.
In order to better understand the role selenium plays in breast cancer, 30 samples of tumor tissue were obtained from women with breast cancer and analyzed for selenium concentration, the levels of several selenium-containing proteins and the levels of the MnSOD anti-oxidant protein.
Statistical analysis revealed that the reduced SOD2 expression in primary tumor tissue is associated with lymph node metastasis in both TSCC patient cohorts examined.
This review focuses on the recent discovery that decreased expression of SOD2, a putative tumor-suppressor gene and the major source of H2O2, results from hypermethylation of CpG islands.
The results presented suggest that SOD2 expression can participate in radioresistance of NPC, being markers of a subset of tumors in which routine radiation treatment failure is likely.
Mice with orthotopic thoracic tumors composed of 32D-v-abl cells that received intraesophageal SOD2-PL treatment showed transgenic mRNA in the esophagus at 24 h, but no detectable human SOD2 transgene mRNA in explanted tumors by nested RT-PCR.
In particular, in cases with metastatic RCC, high SOD2 expression in the tumors was significantly associated with a worse overall survival (p= 0.001), and the maximum critical risk.
The up-regulation of isocitrate dehydrogenase 1 (IDH1), superoxide dismutase 2, 14-3-3ε, and receptor of activated protein kinase C1 and the down-regulation of peroxiredoxin 2 in tumors were validated by RT-PCR and Western blot analysis in independent 15 pairs of samples.
Silencing SOD2 expression upregulates androgen receptor (AR) signaling and expression of SOD2 is downregulated in CRPC, compared with untreated tumors.
Sustained overexpression of SOD2 and GPX1 accounted as risk factors for distant tumour recurrence (P = 0.003) mainly for bone metastases (97% M1b) as evaluated by Kaplan-Meier curves.
In vitro experiments revealed that radiation-induced SOD2 overexpression inhibited tumor cell proliferation (61.89% vs. 40.17%, P < 0.01) and decreased apoptosis among normal cells (14.8% vs. 9.6%, P = 0.02) as compared to untransfected cells.Similar effects were observed in vivo.