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

Overview

Journal J Cancer

Specialty Oncology

Date 2020 Jan 2

PMID 31892992

Citations 19

Authors

Song Hu

Manlin Cao

Yiqing He

Guoliang Zhang

Yiwen Liu

Yan Du

Cuixia Yang

Feng Gao

Affiliations

Soon will be listed here.

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 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.

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References

Qin W, Shi Y, Zhao B, Yao C, Jin L, Ma J . miR-24 regulates apoptosis by targeting the open reading frame (ORF) region of FAF1 in cancer cells. PLoS One. 2010; 5(2):e9429. PMC: 2828487. DOI: 10.1371/journal.pone.0009429. View

Todaro M, Gaggianesi M, Catalano V, Benfante A, Iovino F, Biffoni M . CD44v6 is a marker of constitutive and reprogrammed cancer stem cells driving colon cancer metastasis. Cell Stem Cell. 2014; 14(3):342-56. DOI: 10.1016/j.stem.2014.01.009. View

Fornetti J, Welm A, Stewart S . Understanding the Bone in Cancer Metastasis. J Bone Miner Res. 2018; 33(12):2099-2113. DOI: 10.1002/jbmr.3618. View

Tijink B, Buter J, de Bree R, Giaccone G, Lang M, Staab A . A phase I dose escalation study with anti-CD44v6 bivatuzumab mertansine in patients with incurable squamous cell carcinoma of the head and neck or esophagus. Clin Cancer Res. 2006; 12(20 Pt 1):6064-72. DOI: 10.1158/1078-0432.CCR-06-0910. View

Yamane N, Tsujitani S, Makino M, Maeta M, Kaibara N . Soluble CD44 variant 6 as a prognostic indicator in patients with colorectal cancer. Oncology. 1999; 56(3):232-8. DOI: 10.1159/000011970. View

Echeverria G, Powell E, Seth S, Ge Z, Carugo A, Bristow C . High-resolution clonal mapping of multi-organ metastasis in triple negative breast cancer. Nat Commun. 2018; 9(1):5079. PMC: 6265294. DOI: 10.1038/s41467-018-07406-4. View

Chen C, Zhao S, Karnad A, Freeman J . The biology and role of CD44 in cancer progression: therapeutic implications. J Hematol Oncol. 2018; 11(1):64. PMC: 5946470. DOI: 10.1186/s13045-018-0605-5. View

Ni J, Cozzi P, Hao J, Beretov J, Chang L, Duan W . CD44 variant 6 is associated with prostate cancer metastasis and chemo-/radioresistance. Prostate. 2014; 74(6):602-17. DOI: 10.1002/pros.22775. View

Forman J, Legesse-Miller A, Coller H . A search for conserved sequences in coding regions reveals that the let-7 microRNA targets Dicer within its coding sequence. Proc Natl Acad Sci U S A. 2008; 105(39):14879-84. PMC: 2567461. DOI: 10.1073/pnas.0803230105. View

10.

Takahashi H, Isogawa M . Management of breast cancer brain metastases. Chin Clin Oncol. 2018; 7(3):30. DOI: 10.21037/cco.2018.05.06. View

11.

Weidle U, Maisel D, Klostermann S, Weiss E, Schmitt M . Differential splicing generates new transmembrane receptor and extracellular matrix-related targets for antibody-based therapy of cancer. Cancer Genomics Proteomics. 2011; 8(5):211-26. View

12.

Bray F, Ferlay J, Soerjomataram I, Siegel R, Torre L, Jemal A . Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018; 68(6):394-424. DOI: 10.3322/caac.21492. View

13.

Rehmsmeier M, Steffen P, Hochsmann M, Giegerich R . Fast and effective prediction of microRNA/target duplexes. RNA. 2004; 10(10):1507-17. PMC: 1370637. DOI: 10.1261/rna.5248604. View

14.

Wu L, Belasco J . Let me count the ways: mechanisms of gene regulation by miRNAs and siRNAs. Mol Cell. 2008; 29(1):1-7. DOI: 10.1016/j.molcel.2007.12.010. View

15.

Liu C, Kelnar K, Liu B, Chen X, Calhoun-Davis T, Li H . The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44. Nat Med. 2011; 17(2):211-5. PMC: 3076220. DOI: 10.1038/nm.2284. View

16.

Fang M, Wu J, Lai X, Ai H, Tao Y, Zhu B . CD44 and CD44v6 are Correlated with Gastric Cancer Progression and Poor Patient Prognosis: Evidence from 42 Studies. Cell Physiol Biochem. 2016; 40(3-4):567-578. DOI: 10.1159/000452570. View

17.

Zavros Y . Initiation and Maintenance of Gastric Cancer: A Focus on CD44 Variant Isoforms and Cancer Stem Cells. Cell Mol Gastroenterol Hepatol. 2017; 4(1):55-63. PMC: 5439237. DOI: 10.1016/j.jcmgh.2017.03.003. View

18.

Chen L, Jiang B, Wang Z, Liu M, Yang H, Xing J . Combined preoperative CEA and CD44v6 improves prognostic value in patients with stage I and stage II colorectal cancer. Clin Transl Oncol. 2013; 16(3):285-92. DOI: 10.1007/s12094-013-1069-2. View

19.

Mueller B, Schraufstatter I, Goncharova V, Povaliy T, DiScipio R, Khaldoyanidi S . Hyaluronan inhibits postchemotherapy tumor regrowth in a colon carcinoma xenograft model. Mol Cancer Ther. 2010; 9(11):3024-32. PMC: 2978790. DOI: 10.1158/1535-7163.MCT-10-0529. View

20.

Siegel R, Miller K, Jemal A . Cancer statistics, 2018. CA Cancer J Clin. 2018; 68(1):7-30. DOI: 10.3322/caac.21442. View