Abstract
BackgroundmiR-22 has been shown to be frequently downregulated and act as a tumor suppressor in multiple cancers including breast cancers. However, the role of miR-22 in regulating the radioresistance of breast cancer cells, as well as its underlying mechanism is still not well understood.MethodsThe expressions of miR-22 and sirt1 at mRNA and protein levels were examined by qRT-PCR and Western Blot. The effects of miR-22 overexpression and sirt1 knockdown on cell viability, apoptosis, radiosensitivity, γ-H2AX foci formation were evaluated by CCK-8 assay, flow cytometry, colony formation assay, and γ-H2AX foci formation assay, respectively. Luciferase reporter assay and qRT-PCR analysis were performed to confirm the interaction between miR-22 and sirt1.ResultsmiR-22 was downregulated and sirt1 was upregulated at both mRNA and protein levels in breast cancer cells. miR-22 overexpression or sirt1 knockdown significantly suppressed viability, induced apoptosis, reduced survival fraction, and increased the number of γ-H2AX foci in breast cancer cells. Sirt1 was identified as a target of miR-22 and miR-22 negatively regulated sirt1 expression. Ectopic expression of sirt1 dramatically reversed the inhibitory effect of miR-22 on cell viability and promotive effect on apoptotic rates and radiosensitivity in breast cancer cells.ConclusionsmiR-22 suppresses tumorigenesis and improves radiosensitivity of breast cancer cells by targeting sirt1, providing a promising therapeutic target for breast cancer.
Highlights
MiR-22 has been shown to be frequently downregulated and act as a tumor suppressor in multiple cancers including breast cancers
Results miR‐22 was downregulated and sirt1 was upregulated in breast cancer cells To explore the role of miR-22 and sirt1 in the development of breast cancer, we analyzed the expressions of miR-22 and sirt1 at mRNA and protein levels in breast cancer cells by quantitative real-time PCR (qRT-PCR) and Western Blot
As demonstrated by CCK-8 assay, cell viability was significantly reduced in si-sirt1-transfected MCF-7 (Fig. 3a) and MDA-MB-231 (Fig. 3b) cells compared to control group
Summary
MiR-22 has been shown to be frequently downregulated and act as a tumor suppressor in multiple cancers including breast cancers. The role of miR-22 in regulating the radioresistance of breast cancer cells, as well as its underlying mechanism is still not well understood. It is well known that radiotherapy is currently a major adjuvant treatment for the majority of breast cancer patients [4]. This strategy helps to reduce the risk of recurrence by 70% and improve survival of breast cancer patients [5]. Radioresistance is a major challenge to attaining maximal efficacy for successful radiotherapy of breast cancers [6]. Better understanding the underlying mechanisms involved in radioresistance and developing more effective therapeutic strategy are essential and urgent
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