Key result
miR-618 overexpression cuts TIMP-1 expression ~76% in vitro and is linked to lower Gleason scores.
Why the study?
The regulation of TIMP-1 expression by miR-618 and its effect on prostate cancer cell invasion were unclear, as well as miR-618 expression patterns in localized prostate cancer specimens.
Does miR-618 expression modify TIMP-1 and MMP-9 expression in prostate cancer cells and correlate with disease severity in localized prostate cancer?
Does miR-618 expression modify TIMP-1 and MMP-9 expression in prostate cancer cells and correlate with disease severity in localized prostate cancer?
In vitro, miR-618 overexpression decreases TIMP-1 and its inhibition decreases MMP-9, but in clinical samples, increased miR-618 expression was associated with lower Gleason score and pathological status, suggesting a context-dependent role.
Answers are grounded in this paper and cite their sources.
miR-618 may exert context-dependent effects on TIMP-1; leaves open its role as prognostic biomarker in localized prostate cancer.
BACKGROUND: The imbalance between the action of the tissue inhibitors of matrix metalloproteinases (TIMPs) and the matrix metalloproteinases (MMPs) is one component of metastasis physiology. TIMP-1 overrides MMP-9 activity in cancer and might be regulated by miR-618. The aims of this study were to clarify whether TIMP-1 expression is modified by miR-618 and to clarify the effect of miR-618 expression on the invasion of prostate cancer cells. We also studied miR-618 expression in surgical specimens of patients with localized prostate cancer submitted to open radical prostatectomy. METHODS: After transfection of miR-618 or its antagonist in DU145 cells, qRT-PCR for TIMP-1/MMP-9 and both ELISA and zymography for MMP-9 were performed. Total miRNA was extracted from surgical specimens of PCa, and miR-618 expression was examined for correlations with Gleason score, pathological status and biochemical recurrence. RESULTS: DU145 cells transfected with miR-618 had a 76% reduction in TIMP-1 expression relative to control cells (p = 0.003). miR-618 inhibition reduced MMP-9 expression by 31% (p = 0.032) and MMP-9 absorbance evaluated with ELISA assay (p = 0.06).Zymography suggested higher MMP-9 activity in DU145 cells transfected with miR-618 than those transfected with miR-618 inhibitor, but the difference was not significant (p = 0.55). However, miR-618 expression was lower in surgical specimens of patients with Gleason score > 7 (p = 0.08) and more advanced disease (p = 0.07). CONCLUSIONS: In vitro, miR-618 overexpression decreases TIMP-1 and miR-618 inhibition decreases MMP-9, suggesting that miR-618 might be an oncomiR. However, the analysis of clinical samples of localized prostate cancer revealed an inconsistent pattern, as increased miR-618 expression was associated with lower Gleason score and pathological status. Further studies are needed to address whether miR-618 is a context-dependent miRNA.
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Ivanovic et al. (2018) studied Localized prostate cancer (n=51). miR-618 transfection vs. Control cells was evaluated on TIMP-1 expression (76% reduction, p=0.003). In vitro, miR-618 overexpression reduced TIMP-1 expression by 76% (p=0.003), whereas in clinical samples of localized prostate cancer, higher miR-618 expression was associated with lower Gleason scores.
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