Journal
CLINICAL CANCER RESEARCH
Volume 21, Issue 21, Pages 4881-4891Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-14-2947
Keywords
-
Categories
Funding
- National Natural Science Foundation of China [81372883, 81001052, 81225018, 81401948]
- Science and Technology Planning Project of Guangdong Province, China [2011B031800222]
- Sun Yat-sen University Cancer Center
- Sun Yat-sen University
- Natural Science Foundation of Guangdong Province, China [8151008901000043]
- Sister Institution Network Fund of the MD Anderson Cancer Center
Ask authors/readers for more resources
Purpose: Deregulation of microRNA (miRNA) has been extensively investigated in both Hodgkin and non-Hodgkin lymphomas (NHL); however, little is known about the roles of miRNAs in T-cell lymphoblastic lymphoma (T-LBL). The aim of the present study was to investigate the potential roles of miR-374b in the development and treatment of T-LBL. Experimental Design: MiRCURY LNA array was used to generate a miRNA-expressing profile. Real-time quantitative PCR and immunohistochemistry (IHC) were applied to detect the expression of miR-374b, AKT1, and Wnt16 in T-LBL samples. The dual-luciferase reporter assay was conducted to confirm target associations of miR-374b. The tumor-suppressive effect of miR-374b was determined by both in vitro and in vivo studies. Results: The expression of 380 miRNAs was evaluated in five human T-LBL tissues and five infantile thymus samples by micro-RNA microarrays. Downregulation of miR-374b was frequently detected in primary T-LBL tissues, which was significantly associated with worse overall survival and increased risk of recurrence of the 58 patients enrolled in this study. miR-374b suppressed T-LBL cell proliferation in vitro and in vivo and sensitized cells to serum starvation-and chemotherapeutic agent-induced apoptosis. Furthermore, we characterized two AKT pathway-associated molecules, AKT1 and Wnt16, as direct targets of miR-374b. Consistently, in T-LBL patient tissues, AKT1 and Wnt16 expression was inversely correlated with miR-374b levels, and was an independent predictor of recurrence and survival. Conclusions: Our data highlight the molecular etiology and clinical significance of miR-374b in T-LBL. Targeting miR-374b may represent a new therapeutic strategy to improve therapy and survival for T-LBL patients. (C)2015 AACR.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available