Background:Latest studies have shown that SMAD 7 played a major role in breast cancer during tumour development and progression. In the current study, we aimed to examine the relationship between microRNA-497 (miR-497) and SMAD 7 and its function in MDA-MB-231 breast cancer cells and MCF-7 breast cancer cells. And to investigate the clinicopathologic and prognostic significance of miR-497 expression in human breast cancer.
Quantitative polymerase chain reaction was used to measure the expression levels of miR-497 in 40 breast cancer specimens and adjacent normal breast tissues. MTT assays, colony formation assays and cell cycle assays were used to explore the potential function of miR-497 in MDA-MB-231 breast cancer cells and MCF-7 breast cancer cells. Dual-luciferase reporter assays were performed to analyze the regulation of putative target of miR-497, and western blot assays were used to validate the dual-luciferase results.Also, miR-497 expression was detected in another 240 breast cancer tissues and its correlations with clinicopathologic features of patients were analyzed. Kaplan-Meier analyses were used to assess survival of patients.
The results showed that MiR-497 was downregulated in breast cancer tissues compared with normol tissues(P <0.05). Dual-luciferase reporter assays manifestations that SMAD 7 is the target of miR-497. Quantitative polymerase chain reaction and Western blot assays validated that overexpression of miR-497 can reduce SMAD 7 protein levels, miR-497 can inhibit cellular growth and cause a G1 arrest. Of 240 BC patients, 132 (55%) were placed in the high miR-497 group and 108 (45%) were placed in the low-miR-497 group. By statistical analyses, ,The miR-497 expression levels were significantly lower in HER2-positive and base-like patients than luminal subtype patients (p=0.036). Moreover, patients with high miR-497 expression had better 5-year disease-free and overall survival compared with the low miR-497 group (P = 0.0027and 0.0032, respectively).In the TNBC subtype with high miR-497 expression had better 5-year DFS and OS compared with the low miR-497 group (P = 0.0491 and 0.035). In the HER-2 + subtype with high miR-497 expression had better 5-year DFS and OS compared with the low miR-497 group (P = 0.0142 and P=0.024).
In summary, MiR-497 act as a tumor suppressor gene in breast cancer. Overexpression of miR-497 inhibited cell proliferation and G1 cell cycle arrest were observed. Downregulation of miR-497 was correlated with breast cancer progression and has negative correlation with SMAD7, The above results indicated that miR-497 might be a potential molecular biomarker for predicting the prognosis of patients and miR-497 could be considered an ideal therapeutic target for the HER-2 positive and TNBC breast cancer.
Citation Format: Liu J, Zhang S, Hu Y, Zhang M, Li C, Liu Y, Zhang X, Zhang J. MicroRNA-497 targets SMAD7 and has a tumour suppressive effect and its prognostic significance in breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-03-03.