Redox Regulating Enzymes and Connected MicroRNA Regulators Have Prognostic Value in Classical Hodgkin Lymphomas

Abstract

There are no previous studies assessing the microRNAs that regulate antioxidant enzymes in Hodgkin lymphomas (HLs). We determined the mRNA levels of redox regulating enzymes peroxiredoxins (PRDXs) I–III, manganese superoxide dismutase (MnSOD), nuclear factor erythroid-derived 2-like 2 (Nrf2), and Kelch-like ECH-associated protein 1 (Keap1) from a carefully collected set of 41 classical HL patients before receiving any treatments. The levels of redoxmiRs, miRNAs known to regulate the above-mentioned enzymes, were also assessed, along with CD3, CD20, and CD30 protein expression. RNAs were isolated from freshly frozen lymph node samples and the expression levels were analyzed by qPCR. mir23b correlated inversely with CD3 and CD20 expressions (p = 0.00076; r = −0.523 and p = 0.0012; r = −0.507) and miR144 with CD3, CD20, and CD30 (p = 0.030; r = −0.352, p = 0.041; r = −0.333 and p = 0.0032; r = −0.47, resp.). High MnSOD mRNA levels associated with poor HL-specific outcome in the patients with advanced disease (p = 0.045) and high miR-122 levels associated with worse HL-specific survival in the whole patient population (p = 0.015). When standardized according to the CD30 expression, high miR212 and miR510 predicted worse relapse-free survival (p = 0.049 and p = 0.0058, resp.). In conclusion, several redoxmiRs and redox regulating enzyme mRNA levels associate with aggressive disease outcome and may also produce prognostic information in classical HL.

Expression Levels of microRNAs miR-93 and miR-200a in Pancreatic Adenocarcinoma with Special Reference to Differentiation and Relapse-Free Survival

“…However, Keap1 and Nrf2 mRNA levels in malignant cells and adjacent pancreatic tissue do not seem to play a major prognostic role or be associated with disease aggressiveness. Furthermore, the strong correlation between Nrf2 and Keap1 mRNA levels seen here in both the malignant and the adjacent benign areas, and previously in Hodgkin lymphomas [15], seems to point out a disturbance in regulatory events, likely at the protein level. Kosti et al [25] recently compared extensive mRNA and protein data in various cancer types.…”

“…Expression levels of miRNAs are profoundly altered during carcinogenesis, but alterations in miRNA profiles may also initiate tumour growth and metastasis [12, 13]. Some miRNAs are considered to be “redoxmiRs,” as they have an essential influence on redox-state regulation [14, 15]. For example, miR-93 has been shown to directly repress Nrf2 mRNA [16].…”

MicroRNAs regulating superoxide dismutase 2 are new circulating biomarkers of heart failure

“…LIPCAR is a novel biomarker of cardiac remodeling and predict future death in patients with HF 24 , suggesting potential interest of non-coding RNAs as biomarkers in molecular diagnostics. SOD2 mRNA was recently reported for predicting worse prognosis of patients with untreated classical Hodgkin lymphoma 25 .…”

Strong SOD2 expression and HPV-16/18 positivity are independent events in cervical cancer

“…Such ROS accumulation induces cellular damage that may promote cancer development as well as its metabolic phenotype [ 13 - 15 , 27 ]. In fact, most of the studies about SOD2 expression and cancer have shown that overexpression of this enzyme is associated with the presence of metastases and poor prognosis in many malignancies, such as lymphomas [ 28 , 29 ], glioblastoma [ 30 ], bladder [ 31 ], lung [ 32 ], colorectal [ 33 ], breast [ 34 ], penile [ 35 ], gastric [ 36 ], esophageal [ 37 ] and oral cancer [ 38 ].…”