The prognostic significance of RUNX2 and miR-10a/10b and their inter-relationship in breast cancer

Abstract

BackgroundThe major cancer related mortality is caused by metastasis and invasion. It is important to identify genes regulating metastasis and invasion in order to curtail metastatic spread of cancer cells.MethodsThis study investigated the association between RUNX2 and miR-10a/miR-10b and the risk of breast cancer relapse. Expression levels of RUNX2 and miR-10a/b in108 pairs of tumor and non-tumor tissue of breast cancer were assayed by quantitative PCR analysis and evaluated for their prognostic implications.ResultsThe median expression levels of RUNX2 and miR-10b in tumor tissue normalized using adjacent non-tumor tissue were significantly higher in relapsed patients than in relapse-free patients. Higher expression of these three genes were significantly correlated with the hazard ratio for breast cancer recurrence (RUNX2: 3.02, 95% CI = 1.50 ~ 6.07; miR-10a: 2.31, 95% CI = 1.00 ~ 5.32; miR-10b: 3.96, 95% CI = 1.21 ~ 12.98). The joint effect of higher expression of all three genes was associated with a hazard ratio of 12.37 (95% CI = 1.62 ~ 94.55) for relapse. In a breast cancer cell line, RUNX2 silencing reduced the expression of miR-10a/b and also impaired cell motility, while RUNX2 overexpression elicited opposite effects.ConclusionsThese findings indicate that higher expression of RUNX2 and miR-10a/b was associated with adverse outcome of breast cancer. Expression levels of RUNX2 and miR-10a/b individually or jointly are potential prognostic factors for predicting breast cancer recurrence. Data from in vitro studies support the notion that RUNX2 promoted cell motility by upregulating miR-10a/b.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-014-0257-3) contains supplementary material, which is available to authorized users.

microRNA-10a Targets T-box 5 to Inhibit the Development of Cardiac Hypertrophy

“…More importantly, miR-10a is found to repress TBX5 protein levels by targeting TBX5 3'UTR. 13) In this study, we predicted Tbx5 to be a potential target of miR-10a using an online database and verified their direct binding by dual-luciferase reporter assay. Examination by qRT-PCR and Western blot showed that both mRNA and protein levels of TBX5 were inhibited by miR-10a, suggesting that miR-10a could not only regulate TBX5 post-transcriptionally, but also decrease the level of Tbx5 mRNA, possibly by affecting mRNA stability.…”

“…12) Higher expression of miR-10a may be also associated with an adverse outcome in breast cancer. 13) Moreover, it was reported that miR-10a can regulate the proliferation of human cardiomyocyte progenitor cells. 14) miR-10a was shown to be involved in congenital heart disease by targeting T-box 5 (Tbx5), which is a factor participating in embryonic cardiac development.…”

Thyroid Hormone Receptor-β (TRβ) Mediates Runt-Related Transcription Factor 2 (Runx2) Expression in Thyroid Cancer Cells: A Novel Signaling Pathway in Thyroid Cancer

“…Runt-related transcription factors (Runx 1-3) are key regulators in mesenchymal cell differentiation in osteogenic lineage and of proliferation and differentiation during embryonic development and tissue remodeling (11). In particular, Runx2 is a key regulator of tumorigenesis and functionally linked with tumor progression in breast (12)(13)(14), ovarian epithelial (15), and prostate cancers (16). Activation or increased expression of Runx2, noted particularly in metastatic tumors targeting bone (17)(18)(19)(20), induces an array of genes associated with cell adhesion, invasion, survival as well as increased expression of markers of metastases (21,22).…”

Prognostic significance of microRNA-10b overexpression in breast cancer: a meta-analysis

“…Using the search criteria (Figure 1), a total of 7 publications met the criteria for this analysis (Gee et al, 2008;Radojicic et al, 2011;Liang et al, 2011;Song et al, 2012;Chang et al, 2014;Markou et al, 2014;Parrella et al, 2014). The total number of patients included was 770 ranging from 60 to 219 patients per study.…”

“…Some concluded that miR-10b expression had no influence on survival (Gee et al, 2008;Radojicic et al, 2011;Parrella et al, 2014), while others reported that miR-10b expression was predictive of decreased survival outcome for breast cancer (Liang et al, 2011;Chang et al, 2014). Insufficient samples and some other factors have resulted in controversial results of different clinical studies.…”