MiR-219-5p Targets TBXT and Inhibits Breast Cancer Cell EMT and Cell Migration and Invasion

Overview

Journal Biosci Rep

Specialty Cell Biology

Date 2021 Aug 2

PMID 34339487

Citations 5

Authors

Qin Ye

Xing Wang

Mei Yuan

Shuaishuai Cui

Yuanyuan Chen

Zhaodi Hu

Dandan Liu

Conghui Han

Bibo Li

Dahu Chen

Affiliations

Soon will be listed here.

Abstract

miR-219-5p has been reported to act as either a tumor suppressor or a tumor promoter in different cancers by targeting different genes. In the present study, we demonstrated that miR-219-5p negatively regulated the expression of TBXT, a known epithelial-mesenchymal transition (EMT) inducer, by directly binding to TBXT 3'-untranslated region. As a result of its inhibition on TBXT expression, miR-219-5p suppressed EMT and cell migration and invasion in breast cancer cells. The re-introduction of TBXT in miR-219-5p overexpressing cells decreased the inhibitory effects of miR-219 on EMT and cell migration and invasion. Moreover, miR-219-5p decreased breast cancer stem cell (CSC) marker genes expression and reduced the mammosphere forming capability of cells. Overall, our study highlighted that TBXT is a novel target of miR-219-5p. By suppressing TBXT, miR-219-5p plays an important role in EMT and cell migration and invasion of breast cancer cells.

Citing Articles

The impact of ferroptosis and ferroptosis-related non-coding RNAs on breast cancer progression.

Liu W, Jiang C, Ma Y, Wang W, Peng J, Ma W Front Cell Dev Biol. 2025; 12:1506492.

PMID: 39763590 PMC: 11701165. DOI: 10.3389/fcell.2024.1506492.

Inhibitory Effects of BYB3 Cell-Free Extract on Human Melanoma B16F10 Cells and Tumorigenic Mice.

Li D, Wang X, Park D, Lee D, Oh S J Microbiol Biotechnol. 2023; 34(3):589-595.

PMID: 38044715 PMC: 11016762. DOI: 10.4014/jmb.2309.09002.

MiR-4649-5p acts as a tumor-suppressive microRNA in triple negative breast cancer by direct interaction with PIP5K1C, thereby potentiating growth-inhibitory effects of the AKT inhibitor capivasertib.

Jonas K, Prinz F, Ferracin M, Krajina K, Pasculli B, Deutsch A Breast Cancer Res. 2023; 25(1):119.

PMID: 37803350 PMC: 10559525. DOI: 10.1186/s13058-023-01716-2.

Non-coding RNA's prevalence as biomarkers for prognostic, diagnostic, and clinical utility in breast cancer.

Ali R, Laskar S, Khan N, Wahab S, Khalid M Funct Integr Genomics. 2023; 23(2):195.

PMID: 37270446 DOI: 10.1007/s10142-023-01123-y.

Genetic Polymorphisms in microRNA Genes Targeting PI3K/Akt Signal Pathway Modulate Cervical Cancer Susceptibility in a Chinese Population.

Chen K, Yan Z, Dong X, Liang Y, Yao Y, Zhang S Front Genet. 2022; 13:856505.

PMID: 35495171 PMC: 9047912. DOI: 10.3389/fgene.2022.856505.

References

Mani S, Guo W, Liao M, Eaton E, Ayyanan A, Zhou A . The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell. 2008; 133(4):704-15. PMC: 2728032. DOI: 10.1016/j.cell.2008.03.027. View

Du R, Wu S, Lv X, Fang H, Wu S, Kang J . Overexpression of brachyury contributes to tumor metastasis by inducing epithelial-mesenchymal transition in hepatocellular carcinoma. J Exp Clin Cancer Res. 2014; 33:105. PMC: 4279691. DOI: 10.1186/s13046-014-0105-6. View

Latinkic B, Umbhauer M, Neal K, Lerchner W, Smith J, Cunliffe V . The Xenopus Brachyury promoter is activated by FGF and low concentrations of activin and suppressed by high concentrations of activin and by paired-type homeodomain proteins. Genes Dev. 1998; 11(23):3265-76. PMC: 316753. DOI: 10.1101/gad.11.23.3265. View

Yang J, Weinberg R . Epithelial-mesenchymal transition: at the crossroads of development and tumor metastasis. Dev Cell. 2008; 14(6):818-29. DOI: 10.1016/j.devcel.2008.05.009. View

Wellner U, Schubert J, Burk U, Schmalhofer O, Zhu F, Sonntag A . The EMT-activator ZEB1 promotes tumorigenicity by repressing stemness-inhibiting microRNAs. Nat Cell Biol. 2009; 11(12):1487-95. DOI: 10.1038/ncb1998. View

Zhang J, Ma L . MicroRNA control of epithelial-mesenchymal transition and metastasis. Cancer Metastasis Rev. 2012; 31(3-4):653-62. PMC: 3686549. DOI: 10.1007/s10555-012-9368-6. View

Cheng J, Deng R, Zhang P, Wu C, Wu K, Shi L . miR-219-5p plays a tumor suppressive role in colon cancer by targeting oncogene Sall4. Oncol Rep. 2015; 34(4):1923-32. DOI: 10.3892/or.2015.4168. View

Calin G, Croce C . MicroRNA signatures in human cancers. Nat Rev Cancer. 2006; 6(11):857-66. DOI: 10.1038/nrc1997. View

Long J, Menggen Q, Wuren Q, Shi Q, Pi X . MiR-219-5p Inhibits the Growth and Metastasis of Malignant Melanoma by Targeting BCL-2. Biomed Res Int. 2017; 2017:9032502. PMC: 5572586. DOI: 10.1155/2017/9032502. View

10.

Larue L, Bellacosa A . Epithelial-mesenchymal transition in development and cancer: role of phosphatidylinositol 3' kinase/AKT pathways. Oncogene. 2005; 24(50):7443-54. DOI: 10.1038/sj.onc.1209091. View

11.

Ma L, Teruya-Feldstein J, Weinberg R . Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature. 2007; 449(7163):682-8. DOI: 10.1038/nature06174. View

12.

Matamala N, Vargas M, Gonzalez-Campora R, Minambres R, Arias J, Menendez P . Tumor microRNA expression profiling identifies circulating microRNAs for early breast cancer detection. Clin Chem. 2015; 61(8):1098-106. DOI: 10.1373/clinchem.2015.238691. View

13.

Miller K, Siegel R, Lin C, Mariotto A, Kramer J, Rowland J . Cancer treatment and survivorship statistics, 2016. CA Cancer J Clin. 2016; 66(4):271-89. DOI: 10.3322/caac.21349. View

14.

OConor C, Chen T, Gonzalez I, Cao D, Peng Y . Cancer stem cells in triple-negative breast cancer: a potential target and prognostic marker. Biomark Med. 2018; 12(7):813-820. DOI: 10.2217/bmm-2017-0398. View

15.

Roselli M, Fernando R, Guadagni F, Spila A, Alessandroni J, Palmirotta R . Brachyury, a driver of the epithelial-mesenchymal transition, is overexpressed in human lung tumors: an opportunity for novel interventions against lung cancer. Clin Cancer Res. 2012; 18(14):3868-79. PMC: 3472640. DOI: 10.1158/1078-0432.CCR-11-3211. View

16.

Iv Santaliz-Ruiz L, Xie X, Old M, Teknos T, Pan Q . Emerging role of nanog in tumorigenesis and cancer stem cells. Int J Cancer. 2013; 135(12):2741-8. PMC: 4065638. DOI: 10.1002/ijc.28690. View

17.

Sarkar D, Shields B, Davies M, Muller J, Wakeman J . BRACHYURY confers cancer stem cell characteristics on colorectal cancer cells. Int J Cancer. 2011; 130(2):328-37. DOI: 10.1002/ijc.26029. View

18.

Kalluri R, Weinberg R . The basics of epithelial-mesenchymal transition. J Clin Invest. 2009; 119(6):1420-8. PMC: 2689101. DOI: 10.1172/JCI39104. View

19.

Larocca C, Cohen J, Fernando R, Huang B, Hamilton D, Palena C . An autocrine loop between TGF-β1 and the transcription factor brachyury controls the transition of human carcinoma cells into a mesenchymal phenotype. Mol Cancer Ther. 2013; 12(9):1805-15. PMC: 3815539. DOI: 10.1158/1535-7163.MCT-12-1007. View

20.

Yang J, Sheng Y, Wei J, Gao X, Zhu Y, Jia H . MicroRNA-219-5p Promotes Tumor Growth and Metastasis of Hepatocellular Carcinoma by Regulating Cadherin 1. Biomed Res Int. 2018; 2018:4793971. PMC: 5976989. DOI: 10.1155/2018/4793971. View