Wnt/β-catenin signaling pathway plays a major role in the cancer metastasis. Several microRNAs (miRNAs) are contributed to the inhibition of breast cancer metastasis. Here, we attempted to find novel targets and mechanisms of microRNA-100 (miR-100) in regulating the migration and invasion of breast cancer cells. In this study, we found that miR-100 expression was downregulated in human breast cancer tissues and cell lines. The overexpression of miR-100 inhibited the migration and invasion of MDA-MB-231 breast cancer cells. Inversely, the downregulation of miR-100 increased the migration and invasion of MCF-7 breast cancer cells. Furthermore, FZD-8, a receptor of Wnt/β-catenin signaling pathway, was demonstrated a direct target of miR-100. The overexpression of miR-100 decreased the expression levels not only FZD-8 but also the key components of Wnt/β-catenin pathway, including β-catenin, metalloproteniase-7 (MMP-7), T-cell factor-4 (TCF-4), and lymphoid enhancing factor-1 (LEF-1), and increased the protein expression levels of GSK-3β and p-GSK-3β in MDA-MB-231 cells, and the transfection of miR-100 inhibitor in MCF-7 cells showed the opposite effects. In addition, the expression of miR-100 was negatively correlated with the FZD-8 expression in human breast cancer tissues. Overall, these findings suggest that miR-100 suppresses the migration and invasion of breast cancer cells by targeting FZD-8 and inhibiting Wnt/β-catenin signaling pathway and manipulation of miR-100 may provide a promoting therapeutic strategy for cancer breast treatment.
MiR-100 FZD-8 Breast cancer Wnt/β-catenin signaling pathway Migration Invasion
This is a preview of subscription content, log in to check access.
This work was supported by grants from the National Natural Science Foundation of China (Grant No. 81373427), Program for Liaoning Innovative Research Team in University, LNIRT, China (Grant No. LT2014016), the Liaoning Provincial Science and Technology Program, China (Grant No. 2013225079), Program for Liaoning Excellent Talents in University, China (Grant No. LJQ2014084), and the S&T Projects in Shenyang, China (Grant No. F14-232-6-05).
Minjie Wei and Miao He designed the experiments. Qian Jiang, Huizhe Wu, Zhaojin Yu, Longyang Jiang, Yan Wang, and Xingyue Zong performed the experiments. Qian Jiang, Mengtao Ma, and Miao He analyzed the data. Shu Guan and Feng Jin gave technical and material support. Miao He, Qian Jiang, and Minjie Wei wrote and reviewed the manuscript.
Klemm F, Bleckmann A, Siam L, Chuang HN, Rietkotter E, Behme D, et al. beta-catenin-independent WNT signaling in basal-like breast cancer and brain metastasis. Carcinogenesis. 2011;32(3):434–42. doi:10.1093/carcin/bgq269.CrossRefPubMedGoogle Scholar
Serafino A, Moroni N, Zonfrillo M, Andreola F, Mercuri L, Nicotera G, et al. WNT-pathway components as predictive markers useful for diagnosis, prevention and therapy in inflammatory bowel disease and sporadic colorectal cancer. Oncotarget. 2014;5(4):978–92.CrossRefPubMedPubMedCentralGoogle Scholar
Zheng YS, Zhang H, Zhang XJ, Feng DD, Luo XQ, Zeng CW, et al. MiR-100 regulates cell differentiation and survival by targeting RBSP3, a phosphatase-like tumor suppressor in acute myeloid leukemia. Oncogene. 2012;31(1):80–92. doi:10.1038/onc.2011.208.CrossRefPubMedGoogle Scholar
Li ZP, Li X, Yu C, Wang M, Peng F, Xiao J, et al. MicroRNA-100 regulates pancreatic cancer cells growth and sensitivity to chemotherapy through targeting FGFR3. Tumor Biol. 2014;35(12):11751–9. doi:10.1007/s13277-014-2271-8.CrossRefGoogle Scholar
Ma MT, He M, Wang Y, Jiao XY, Zhao L, Bai XF, et al. MiR-487a resensitizes mitoxantrone (MX)-resistant breast cancer cells (MCF-7/MX) to MX by targeting breast cancer resistance protein (BCRP/ABCG2). Cancer Lett. 2013;339(1):107–15. doi:10.1016/j.canlet.2013.07.016.CrossRefPubMedGoogle Scholar
Han HS, Son SM, Yun J, Jo YN, Lee OJ. MicroRNA-29a suppresses the growth, migration, and invasion of lung adenocarcinoma cells by targeting carcinoembryonic antigen-related cell adhesion molecule 6. FEBS Lett. 2014;588(20):3744–50. doi:10.1016/j.febslet.2014.08.023.CrossRefPubMedGoogle Scholar
Nishikawa R, Goto Y, Kojima S, Enokida H, Chiyomaru T, Kinoshita T, et al. Tumor-suppressive microRNA-29s inhibit cancer cell migration and invasion via targeting LAMC1 in prostate cancer. Int J Oncol. 2014;45(1):401–10. doi:10.3892/ijo.2014.2437.PubMedGoogle Scholar
Petrelli A, Carollo R, Cargnelutti M, Iovino F, Callari M, Cimino D, et al. By promoting cell differentiation, miR-100 sensitizes basal-like breast cancer stem cells to hormonal therapy. Oncotarget. 2015;6(4):2315–30.CrossRefPubMedGoogle Scholar
Subramanian M, Rao SR, Thacker P, Chatterjee S, Karunagaran D. MiR-29b downregulates canonical Wnt signaling by suppressing coactivators of beta-catenin in human colorectal cancer cells. J Cell Biochem. 2014;115(11):1974–84. doi:10.1002/jcb.24869.PubMedGoogle Scholar