J Cancer 2020; 11(1):260-271. doi:10.7150/jca.35067 This issue

Research Paper

CD44v6 Targeted by miR-193b-5p in the Coding Region Modulates the Migration and Invasion of Breast Cancer Cells

Song Hu1†, Manlin Cao2†, Yiqing He1, Guoliang Zhang1, Yiwen Liu1, Yan Du1, Cuixia Yang, Feng Gao1,3✉

1. Department of Molecular Biology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
2. Department of Rehabilitation Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
3. Department of Clinical Laboratory, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
These authors contributed equally to this work.

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Citation:
Hu S, Cao M, He Y, Zhang G, Liu Y, Du Y, Yang C, Gao F. CD44v6 Targeted by miR-193b-5p in the Coding Region Modulates the Migration and Invasion of Breast Cancer Cells. J Cancer 2020; 11(1):260-271. doi:10.7150/jca.35067. Available from https://www.jcancer.org/v11p0260.htm

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Abstract

Previous studies have shown that CD44 containing variant exon v6 (CD44v6) is highly expressed in many cancers and is related to tumor metastasis. However, the detailed mechanism of the regulatory pattern of CD44v6 in breast cancer remains unclear. Here, we found that CD44v6 was significantly upregulated in invasive breast cancer cell lines compared with low-invasive breast cancer cell lines. Cell migration and invasion could be suppressed by CD44v6 downregulation. MiRWalk and RNAhybrid software revealed miR-193b-5p as a miRNA targeting CD44v6 by binding to the exon v6 region. We found that the overexpression of miR-193b-5p inhibited the migration and invasion of Hs-578t and BT-549 cells, which could be rescued by restoring the expression of CD44v6. Next, we determined the potential of miR-193b-5p as an in vitro biomarker for breast cancer. Serum samples were obtained from 58 breast cancer patients, 36 patients with benign disease and 58 age-matched cancer-free controls. The results showed that the expression of miR-193b-5p in the serum was significantly lower in breast cancer patients than in controls and could distinguish cancer from cancer-free samples. The area under the receiver operating characteristic curve (ROC) for miR-193b-5p was 0.762(95% confidence interval: 0.674-0.851), which was higher than that of carcinoembryonic antigen (CEA) and cancer antigen 15-3 (CA15-3). Combining miR-193b-5p with CEA or CA15-3 could improve the diagnostic efficiency compared with the CEA and CA15-3 combination. Taken together, our results suggest that miR-193b-5p could function as a tumor-suppressive miRNA by targeting CD44v6 in breast cancer and that serum miR-193b-5p may serve as a biomarker for breast cancer diagnosis.

Keywords: Breast cancer, miR-193b-5p, migration, invasion, biomarker