microRNA-497 Modulates Breast Cancer Cell Proliferation, Invasion, and Survival by Targeting SMAD7.
As an inhibitor of TGF-β signaling, SMAD7 was reported to play dual roles in breast cancer development and progression. It inhibited the cancer metastasis by blocking epithelial-mesenchymal transition, however, litter studies focused on its role in other cancer processes. In this study, miR-497 expression was found inversely correlated with SMAD7 expression in breast cancer tissues. Bioinformatics analyses defined a potential miR-497 response element within 3' untranslated region of SMAD7 that was validated in reporter gene experiments. Enforced miR-497 expression, accompanied with SMAD7 reduction, suppressed MDA-MB-231 and MCF-7 breast cancer cell growth by MTT and invasion assay, and, induced the S phase arrest detected by flow cytometry. Furthermore, upregulated miR-497 expression by mimics treatment significantly suppressed the tumor growth in the orthotopic nude mouse models. Finally, high expression of miR-497 conferred a better prognosis, indicated by Kaplan-Meier test, especially in HER2 overexpression and triple-negative breast cancer (TNBC). Taken together, our results identified the proliferation promoting role of SMAD7 in breast cancer and therefore established the regulations of SMAD7 in breast cancer by miR-497 through a posttranscriptional mechanism. Moreover, miR-497 might be deemed as a novel potential therapeutic target for the HER2 positive and TNBC in future.
1 Third Department of Breast Cancer, China Tianjin Breast Cancer Prevention, Treatment and Research Center, Tianjin Medical University Cancer Institute and Hospital , National Clinical Research Center of Cancer, Tianjin, People's Republic of China .|2 Key Laboratory of Breast Cancer Prevention and Therapy of Ministry of Education , Tianjin, People's Republic of China .|3 Key Laboratory of Cancer Prevention and Therapy , Tianjin, People's Republic of China .
Jingjing
J
Liu
1 Third Department of Breast Cancer, China Tianjin Breast Cancer Prevention, Treatment and Research Center, Tianjin Medical University Cancer Institute and Hospital , National Clinical Research Center of Cancer, Tianjin, People's Republic of China .|2 Key Laboratory of Breast Cancer Prevention and Therapy of Ministry of Education , Tianjin, People's Republic of China .|3 Key Laboratory of Cancer Prevention and Therapy , Tianjin, People's Republic of China .
Yang
Y
Zhou
1 Third Department of Breast Cancer, China Tianjin Breast Cancer Prevention, Treatment and Research Center, Tianjin Medical University Cancer Institute and Hospital , National Clinical Research Center of Cancer, Tianjin, People's Republic of China .|2 Key Laboratory of Breast Cancer Prevention and Therapy of Ministry of Education , Tianjin, People's Republic of China .|3 Key Laboratory of Cancer Prevention and Therapy , Tianjin, People's Republic of China .
Zhendong
Z
Shi
1 Third Department of Breast Cancer, China Tianjin Breast Cancer Prevention, Treatment and Research Center, Tianjin Medical University Cancer Institute and Hospital , National Clinical Research Center of Cancer, Tianjin, People's Republic of China .|2 Key Laboratory of Breast Cancer Prevention and Therapy of Ministry of Education , Tianjin, People's Republic of China .|3 Key Laboratory of Cancer Prevention and Therapy , Tianjin, People's Republic of China .
Yunhui
Y
Hu
1 Third Department of Breast Cancer, China Tianjin Breast Cancer Prevention, Treatment and Research Center, Tianjin Medical University Cancer Institute and Hospital , National Clinical Research Center of Cancer, Tianjin, People's Republic of China .|2 Key Laboratory of Breast Cancer Prevention and Therapy of Ministry of Education , Tianjin, People's Republic of China .|3 Key Laboratory of Cancer Prevention and Therapy , Tianjin, People's Republic of China .
Tingting
T
Meng
1 Third Department of Breast Cancer, China Tianjin Breast Cancer Prevention, Treatment and Research Center, Tianjin Medical University Cancer Institute and Hospital , National Clinical Research Center of Cancer, Tianjin, People's Republic of China .|2 Key Laboratory of Breast Cancer Prevention and Therapy of Ministry of Education , Tianjin, People's Republic of China .|3 Key Laboratory of Cancer Prevention and Therapy , Tianjin, People's Republic of China .
Xiaobei
X
Zhang
1 Third Department of Breast Cancer, China Tianjin Breast Cancer Prevention, Treatment and Research Center, Tianjin Medical University Cancer Institute and Hospital , National Clinical Research Center of Cancer, Tianjin, People's Republic of China .|2 Key Laboratory of Breast Cancer Prevention and Therapy of Ministry of Education , Tianjin, People's Republic of China .|3 Key Laboratory of Cancer Prevention and Therapy , Tianjin, People's Republic of China .
Sheng
S
Zhang
1 Third Department of Breast Cancer, China Tianjin Breast Cancer Prevention, Treatment and Research Center, Tianjin Medical University Cancer Institute and Hospital , National Clinical Research Center of Cancer, Tianjin, People's Republic of China .|2 Key Laboratory of Breast Cancer Prevention and Therapy of Ministry of Education , Tianjin, People's Republic of China .|3 Key Laboratory of Cancer Prevention and Therapy , Tianjin, People's Republic of China .
Jin
J
Zhang
D000328:Adult; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009843:Oligoribonucleotides / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D059807:S Phase Cell Cycle Checkpoints / Q000235:genetics; D015398:Signal Transduction; D051906:Smad7 Protein / Q000235:genetics* / Q000378:metabolism; D016019:Survival Analysis; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
C559640:MIRN497 microRNA, human; D035683:MicroRNAs; D009843:Oligoribonucleotides; C497806:SMAD7 protein, human; D051906:Smad7 Protein