Abstract. The WW domain-containing oxidoreductase (WWOX) gene which encompasses the common human fragile site FRA16D has been proposed as a putative tumor suppressor gene, and loss of WWOX expression has been found in several types of solid cancer. As the role of WWOX in human leukemia has not yet been fully elucidated, the present study examined the expression of WWOX in patients with different types of leukemia as well as in leukemia-derived cell lines. Based on the data, WWOX mRNA (WWOX) and protein (Wwox) were significantly reduced or absent in the leukemia patients as well as in the cell lines. In addition, a recombinant expression vector, pGC-FU-WWOX, was constructed and transfected WWOX cDNA into Jurkat cells (acute T-lymphoblastic leukemia) and K562 cells (chronic myeloid leukemia in erythroid crisis) which all lack endogenous Wwox. In vitro experiments indicated that restoration of Wwox in Jurkat and K562 cells significantly suppressed proliferation and colony formation. Of note, apoptosis was also induced by Wwox restoration. Furthermore, we traced the mechanisms underlying this process and found that Wwox restoration could trigger the mitochondrial pathway in leukemia. Our data provide evidence that WWOX exerts a role as a tumor suppressor gene in leukemia, possibly by inhibiting proliferation and promoting apoptosis via the mitochondrial pathway.

Abstract. The role of the WW domain-containing oxidoreductase (WWOX) gene in multiple types of solid human cancers has been documented extensively thus far. Recently, we investigated the in vitro effects of WWOX overexpression and observed marked growth arrest in human leukemia cells; however, the clinical characterization of WWOX in leukemia remains poorly investigated. The present study evaluated the WWOX expression profiles of 182 patients with leukemia of different types and 5 leukemic cell lines, using reverse transcription-polymerase chain reaction and immunofluorescence analysis. The results found that WWOX mRNA and WWOX protein expression was significantly reduced or absent in the leukemia cases and cell lines compared with paired controls. The WWOX-positive rate was also lower in the leukemia cases compared with the rate of the normal controls. Notably, the WWOX level was reduced in newly diagnosed and relapsed cases, or in chronic myelogenous leukemia in the blastic phase, yet elevated in remission samples. Moreover, WWOX-negative cases exhibited WWOX expression restoration following induced remission. These findings suggest that WWOX may contribute to the occurrence and development of leukemia, and that it has potential to be a good biomarker or predictor for leukemia therapy.

Background MicroRNA‐126 (miR‐126) has been investigated in autoimmune diseases and organ failures, whereas its implication in sepsis is rarely reported. Our study initially explored the value of miR‐126 in diagnosing sepsis and predicting disease severity, degree of inflammation, and mortality. Methods Totally, 208 sepsis patients and 210 healthy controls were enrolled; then, their plasma samples were collected for detecting circulating miR‐126 by quantitative polymerase chain reaction. For sepsis patients, their cytokine levels in plasma samples were detected by enzyme‐linked immunosorbent assay. Results miR‐126 was upregulated in sepsis patients compared with healthy controls, and it was of certain value in distinguishing sepsis patients from healthy controls (AUC: 0.726 (95% CI: 0.678‐0.774)). miR‐126 expression was positively correlated with acute physiology and chronic health evaluation II score, serum creatinine, and C‐reactive protein but not albumin or white blood cell count in sepsis patients. Regarding cytokines, miR‐126 was positively correlated with tumor necrosis factor‐α, interleukin (IL)‐6, and IL‐8, but negatively correlated with IL‐10 in sepsis patients. As for mortality, miR‐126 expression was higher in deaths compared with survivors, and ROC curve displayed that it could predict mortality of sepsis patients to some extent with AUC of 0.619 (95% CI: 0.533‐0.705). Conclusion miR‐126 potentially serves as an assistant diagnostic and prognostic biomarker for sepsis.

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