miR-503-3p promotes epithelial–mesenchymal transition in breast cancer by directly targeting SMAD2 and E-cadherin

a.
State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
b.
Qiqihar Medical University, Qiqihar 161000, China

More Information

Corresponding author: E-mail address: songym@cicams.ac.cn (Yongmei Song)

These authors contributed equally to this work.

摘要

- /
- /
- /
- /
Abstract: Although progress in clinical and basic research has significantly increased our understanding of breast cancer, little is known about the molecular mechanism underlying breast cancer metastasis. Identification of effective therapeutic targets to prevent breast cancer metastasis is urgently needed. The function of miR-503-3p has been investigated in other cancers, but its role in breast cancer remains undefined. Here, we found that miR-503-3p was overexpressed in breast cancer tissue and plasma compared with adjacent normal breast tissue and with plasma from healthy individuals. Moreover, we identified miR-503-3p to be an oncogene of breast cancer cell proliferation, migration and invasion. Upregulation of miR-503-3p in breast cancer cells inhibited expression of epithelial–mesenchymal transition (EMT)-related protein SMAD2 and the epithelial marker protein E-cadherin by directly binding to their mRNA 3′ untranslated region, whereas increased expression of mesenchymal marker proteins, including vimentin and N-cadherin. Taken together, our findings support a critical role for miR-503-3p in induction of breast cancer EMT and suggest that plasma miR-503-3p may be a useful diagnostic biomarker for breast cancer.
- Breast cancer /
- miR-503-3p /
- Plasma miRNA /
- SMAD2 /
- E-cadherin
These authors contributed equally to this work.
注释:

HTML全文

参考文献(23)

[1]	Chan, S.H., Huang, W.C., Chang, J.W. et al. MicroRNA-149 targets GIT1 to suppress integrin signaling and breast cancer metastasis Oncogene, 33 (2014),pp. 4496-4507
[2]	Heerboth, S., Housman, G., Leary, M. et al. EMT and tumor metastasis Clin. Transl. Med., 4 (2015),p. 6
[3]	Holm, J., Li, J., Darabi, H. et al. Associations of breast cancer risk prediction tools with tumor characteristics and metastasis J. Clin. Oncol., 34 (2016),pp. 251-258
[4]	Kimbung, S., Johansson, I., Danielsson, A. et al. Transcriptional profiling of breast cancer metastases identifies liver metastasis-selective genes associated with adverse outcome in luminal a primary breast cancer Clin. Cancer Res., 22 (2016),pp. 146-157
[5]	Li, B.S., Zuo, Q.F., Zhao, Y.L. et al. MicroRNA-25 promotes gastric cancer migration, invasion and proliferation by directly targeting transducer of ERBB2, 1 and correlates with poor survival Oncogene, 34 (2015),pp. 2556-2565
[6]	Li, H., Wang, Z., Zhang, W. et al. Fbxw7 regulates tumor apoptosis, growth arrest and the epithelial-to-mesenchymal transition in part through the RhoA signaling pathway in gastric cancer Cancer Lett., 370 (2016),pp. 39-55
[7]	Li, N.S., Zou, J.R., Lin, H. et al. LKB1/AMPK inhibits TGF-beta1 production and the TGF-beta signaling pathway in breast cancer cells Tumour Biol., 37 (2016),pp. 8249-8258
[8]	Liu, L., Zhao, Z., Zhou, W. et al. Enhanced expression of miR-425 promotes esophageal squamous cell carcinoma tumorigenesis by targeting SMAD2 J. Genet. Genomics, 42 (2015),pp. 601-611
[9]	Megiorni, F., Cialfi, S., McDowell, H.P. et al. Deep sequencing the microRNA profile in rhabdomyosarcoma reveals down-regulation of miR-378 family members BMC Cancer, 14 (2014),p. 880
[10]	Su, C.M., Wang, M.Y., Hong, C.C. et al. miR-520h is crucial for DAPK2 regulation and breast cancer progression Oncogene, 35 (2016),pp. 1134-1142
[11]	Sun, B., Xie, C., Zheng, T. et al. Selecting molecular therapeutic drug targets based on the expression profiles of intrahepatic cholangiocarcinomas and miRNA-mRNA regulatory networks Oncol. Rep., 35 (2016),pp. 382-390
[12]	Syed, V. TGF-beta signaling in cancer J. Cell. Biochem., 117 (2016),pp. 1279-1287
[13]	Varmeh, S., Vanden Borre, P., Gunda, V. et al. Genome-wide analysis of differentially expressed miRNA in PLX4720-resistant and parental human thyroid cancer cell lines Surgery, 159 (2016),pp. 152-162
[14]	Wittchen, E.S., Hartnett, M.E. The small GTPase Rap1 is a novel regulator of RPE cell barrier function Invest. Ophthalmol. Vis. Sci., 52 (2011),pp. 7455-7463
[15]	Xu, X., Zhang, Y., Liu, Z. et al. miRNA-532-5p functions as an oncogenic microRNA in human gastric cancer by directly targeting RUNX3 J. Cell. Mol. Med., 20 (2016),pp. 95-103
[16]	Yamada, A., Cox, M.A., Gaffney, K.A. et al. Technical factors involved in the measurement of circulating microRNA biomarkers for the detection of colorectal neoplasia PLoS One, 9 (2014),p. e112481
[17]	Yin, K., Yin, W., Wang, Y. et al. MiR-206 suppresses epithelial mesenchymal transition by targeting TGF-beta signaling in estrogen receptor positive breast cancer cells Oncotarget, 7 (2016),pp. 24537-24548
[18]	Yoruker, E.E., Holdenrieder, S., Gezer, U. Blood-based biomarkers for diagnosis, prognosis and treatment of colorectal cancer Clin. Chim. Acta, 455 (2016),pp. 26-32
[19]	Yuan, D., Li, K., Zhu, K. et al. Plasma miR-183 predicts recurrence and prognosis in patients with colorectal cancer Cancer Biol. Ther., 16 (2015),pp. 268-275
[20]	Zhao, Y.Y., Wang, W.A., Hu, H. Treatment with recombinant tissue plasminogen activator alters the microRNA expression profiles in mouse brain after acute ischemic stroke Neurol. Sci., 36 (2015),pp. 1463-1470
[21]	Zhong, Y., Pei, Y.H., Wang, J. et al. MicroRNA expression profile in myocardial bridging patients Scand. J. Clin. Lab. Invest., 74 (2014),pp. 582-587
[22]	Zhou, J., Zhang, J. Identification of miRNA-21 and miRNA-24 in plasma as potential early stage markers of acute cerebral infarction Mol. Med. Rep., 10 (2014),pp. 971-976
[23]	Zhu, X., Zhong, J., Zhao, Z. et al. Epithelial derived CTGF promotes breast tumor progression via inducing EMT and collagen I fibers deposition Oncotarget, 6 (2015),pp. 25320-25338