Prognostic significance of miRNA-223 targeting SOX11 in mantle cell lymphoma
10.3760/cma.j.issn.0253-2727.2018.07.010
- VernacularTitle: miR-223靶向调控SOX11在套细胞淋巴瘤中的预后意义
- Author:
Qing ZHANG
1
;
Wentao ZHANG
;
Shengsheng WU
;
Jingjing YUAN
;
Long TIAN
;
Yanyan LIU
;
Wenli ZUO
;
Yongping SONG
;
Keshu ZHOU
Author Information
1. Department of Hematology, the Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou 450008, China
- Publication Type:Journal Article
- Keywords:
MicroRNAs;
Mantle cell lymphoma;
SOX11 transcription factor
- From:
Chinese Journal of Hematology
2018;39(7):579-583
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the expression and prognostic significance of miR-223 in patients with mantle cell lymphoma (MCL) and to investigate the possible mechanism.
Methods:Twenty-one newly diagnosed MCL patients with bone marrow involvement were enrolled in the present study, 20 healthy donors as normal control. The expression level of miR-223 and SOX11 mRNA was determined by RQ-PCR. CCK-8 and flow cytometer assays were used to analyze cell proliferation, cell cycle and apoptosis of the constructed miR-223 overexpressing MCL cell line, Granta519 cells. SOX11 protein expression level was determined by Western blot. The target gene of miR-223 was confirmed by dual luciferase reporter assay.
Results:①Of the 21 newly diagnosed MCL patients, 15 were male and 6 female, the median age was 58 (37-72) years. The expression level of miR-223 was significantly down regulated in MCL patients compared with that of healthy donors (14.7±10.5 vs 1 244.1±1 935.2, P<0.001). The lower expression of miR-223 was inversely correlated with high-risk mantle international prognostic index (P=0.001), elevated LDH (P=0.001), ECOG score ≥2 (P=0.035). ②Using the median relative expression level of miR-223 as the cutoff value, 21 MCL patients were divided into high-expression group (n=10) and low-expression group (n=11) and found that the high-expression group had a significantly superior OS (median OS: 36 vs 12 months, P=0.021). ③In vitro results showed that compared with the control group, the proliferation of miR-223 overexpressed Granta519 cells was inhibited (the most significant reduction on 96h, P<0.001), manifested by lower proportion of cells in G2/M phase (P<0.001) and increased apoptosis (P<0.001), and the expression level of SOX11 protein in Granta519 cells was significantly lower than that of the control group. ④miR-223 could inhibited the 3′ untranslated region of SOX11, and the expression level of miR-223 was significantly negatively correlated with mRNA level of SOX11 in MCL patients (r=-0.81, P<0.001).
Conclusions:The expression of miR-223 was repressed in MCL and was associated with poor clinical outcomes, which may be probably attributed to its direct targeting SOX11.
