Overexpression of BAMBI and SMAD7 impacts prognosis of acute myeloid leukemia patients: A potential TERT non-canonical role.

BACKGROUND: Bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) and mothers against decapentaplegic homolog 7 (SMAD7) are important transforming growth factor-ß (TGF-ß) signaling antagonists, however their roles in acute myeloid leukemia (AML) remains unclear. Telomerase reverse transcriptase (TERT) may be involved in regulating BAMBI and SMAD7 expressions; a role beyond telomeres that is not clinically validated yet. OBJECTIVE: In this study, we examined the expression levels and prognostic values of BAMBI, SMAD7 and TERT and their association with AML patients' outcomes. METHODS: Blood samples were collected from 74 de-novo AML patients and 16 controls. Real-time quantitative PCR (qRT-PCR) was performed to analyze BAMBI, SMAD7 and TERT expressions. RESULTS: BAMBI and SMAD7 expression in AML were significantly upregulated versus controls (p< 0.05). BAMBI, SMAD7 and TERT levels were significantly correlated together (p< 0.001). Kaplan-Meier analysis indicated that patients with high BAMBI, SMAD7 and TERT expression levels had markedly shorter event free survival (EFS) and overall survival (OS) time (p< 0.01). Furthermore, multivariate analysis revealed that only high BAMBI expression was an independent risk factor for OS (p= 0.001). CONCLUSIONS: BAMBI is a novel biomarker in predicting prognosis in AML patients. Moreover, a potential interplay is found between BAMBI, SMAD7 and TERT in AML pathogenies.

Serum Vitamin D and Its Upregulated Protein, Thioredoxin Interacting Protein, Are Associated With Beta-Cell Dysfunction in Adult Patients With Type 1 and Type 2 Diabetes.

OBJECTIVES: Diabetes mellitus is characterized by either complete deficiency of insulin secretion, as in type 1 diabetes, or decompensation of the pancreatic beta cells in type 2 diabetes. Both vitamin D (vitD) and thioredoxin interacting protein (TXNIP) have been shown to be involved in beta-cell dysfunction. Therefore, this study was designed to examine vitD and TXNIP serum levels in patients with diabetes and to correlate these levels with beta-cell function markers in both types of diabetes. METHODS: The routine biochemical parameters and the serum levels of vitD and TXNIP were measured in 20 patients with type 1 diabetes and 20 patients with type 2 diabetes. The levels were then compared to those of 15 healthy control volunteers. Insulin, C-peptide and proinsulin (PI), vitD and TXNIP were measured by ELISA. Beta-cell dysfunction was assessed by homeostatic model assessment (HOMA-beta), proinsulin-to-C-peptide (PI/C) and proinsulin-to-insulin (PI/I) ratios. Correlations among various parameters were studied. RESULTS: Patients with type 1 diabetes had significantly lower HOMA-beta, vitD and TXNIP levels; however, they had higher PI/C levels than the control group. Meanwhile, patients with type 2 diabetes had significantly higher C-peptide, proinsulin, PI/C, HOMA-insulin resistance (HOMA-IR) and lower HOMA-beta and vitD levels, with no significant difference in TXNIP levels as compared to the control group. In addition, vitD was significantly correlated positively with HOMA-beta and TXNIP and negatively with PI, PI/C, PI/I and HOMA-IR. TXNIP correlated positively with HOMA-beta and negatively with PI/C. CONCLUSIONS: Our data showed that vitD and TXNIP were associated with different beta-cell dysfunction markers, indicating their potential abilities to predict the beta-cell status in people with diabetes.

REST regulates oncogenic properties of glioblastoma stem cells.

Glioblastoma multiforme (GBM) tumors are the most common malignant primary brain tumors in adults. Although many GBM tumors are believed to be caused by self-renewing, glioblastoma-derived stem-like cells (GSCs), the mechanisms that regulate self-renewal and other oncogenic properties of GSCs are only now being unraveled. Here we showed that GSCs derived from GBM patient specimens express varying levels of the transcriptional repressor repressor element 1 silencing transcription factor (REST), suggesting heterogeneity across different GSC lines. Loss- and gain-of-function experiments indicated that REST maintains self-renewal of GSCs. High REST-expressing GSCs (HR-GSCs) produced tumors histopathologically distinct from those generated by low REST-expressing GSCs (LR-GSCs) in orthotopic mouse brain tumor models. Knockdown of REST in HR-GSCs resulted in increased survival in GSC-transplanted mice and produced tumors with higher apoptotic and lower invasive properties. Conversely, forced expression of exogenous REST in LR-GSCs produced decreased survival in mice and produced tumors with lower apoptotic and higher invasive properties, similar to HR-GSCs. Thus, based on our results, we propose that a novel function of REST is to maintain self-renewal and other oncogenic properties of GSCs and that REST can play a major role in mediating tumorigenicity in GBM.