Abstract 531: MiR-199a-5p is a biomarker for and regulator of epithelial-mesenchymal transition in triple-negative breast cancer patients

Abstract

Objectives: Triple-negative breast cancer (TNBC) accounts for 15-20% of all breast cancer, and is characterized by the absence of estrogen receptor, progesterone receptor and human epidermal growth factor receptor. The lack of targeted therapy is a major obstacle for treating against this aggressive subtype, hence the search of specific biomarkers may use as potential diagnostic marker and perhaps a therapeutic target for TNBC. Methods: Plasma samples from patients with TNBC and non-TNBC were recruited for miRNA profiling. By using miRCURY LNA array containing 730 miRNAs, we compared the differential miRNA expressions in plasma of patient with TNBC (n=5) and non-TNBC (n=5), as well as healthy controls (n=5). Selected miRNAs were further validated in an independent cohort (n=250) using real-time RT-PCR. Functional study of miRNA was also carried out in the cell lines. Results: Microarray data revealed miR-16, miR-21 and miR-199a-5p have differentially expression between TNBC and non-TNBC. We found that miR-16, miR-21 and miR-199a-5p were underexpressed in TNBC cases when compared with healthy controls. Moreover, post-operative expression levels of miR-16, miR-21 and miR-199a-5p were significantly increased than that of pre-operative plasma of TNBC. We then stratified the patients by TNM stage and associate with miRNA expression level. Plasma miR-199a-5p expression in TNBC patients had significant difference when compared with healthy controls (stage I, p<0.002; stage II, p<0.001; stage III, p<0.011). Transfection of miR-199a-5p mimic significantly reduced cell proliferation and restored the epithelial-mesenchymal transition (EMT) markers (E-cadherin, ZEB1 and TWIST2). Conclusions: Our data implicate that miR-199a-5p is a potential marker for discriminating TNBC cases and non-TNBC cases. The association of miR-199a-5p with EMT markers uncovers an important pathway in metastatic breast cancer. This study provides insights for the potential use of miRNA as diagnostic marker and targeted therapy for the treatment of TNBC. Citation Format: Vivian Y. Shin, Man T. Siu, John C. Ho, Ava Kwong. MiR-199a-5p is a biomarker for and regulator of epithelial-mesenchymal transition in triple-negative breast cancer patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 531. doi:10.1158/1538-7445.AM2014-531

LncRNA PRKCQ‐AS1 regulates paclitaxel resistance in triple‐negative breast cancer cells through miR‐361‐5p/PIK3C3 mediated autophagy

“…Some lncRNAs promote the occurrence and progression of TNBC by regulating their target molecules, showing the characteristics of oncogenes 33 . Other lncRNAs are characterized by tumour suppressor genes and their abnormal expression is closely associated with tumour development or malignant progression 34 .…”

“…Some lncRNAs promote the occurrence and progression of TNBC by regulating their target molecules, showing the characteristics of oncogenes. 33 Other lncRNAs are characterized by tumour suppressor genes and their abnormal expression is closely associated with tumour development or malignant progression. 34 We found lncRNA PRKCQ-AS1 might interact with miR-361-5p through bioanalysis, and was confirmed that lncRNA PRKCQ-AS1 level was up-regulated in TNBC PTX-resistant cells.…”

Review From the lab to the hospital: new ideas in miRNA medicine

“…Similar to the off-target effects seen with other exogenous RNAs, miRNA therapeutic dosage is often beyond the normal range of endogenous miRNA production [97,98]. The genes that are being targeted by the modified miRNA are directly affected by the dosage of miRNA therapies due to the dose dependence of miRNA-target interactions.…”

“…Therapeutic treatments use a variety of methods to obtain effective dosage. One proposed approach to minimizing the therapeutic dosages of individual miRNAs is to use a network of cooperative miRNAs [98]. Vector-based expression systems are another alternative, since they use endogenous promoter sequences to ensure physiologically appropriate and tissue-specific expression levels [22,102].…”

The Anticancer Effects of Flavonoids through miRNAs Modulations in Triple-Negative Breast Cancer

“…The downregulation or loss of tumor suppressor miRNA can be overcome by either using ectopic expression of synthetic miRNA mimics [177,178] or utilizing adenovirusassociated transduction vectors of target cells [179][180][181]. MicroRNA analogs are used to restore miRNAs function; this approach is known as miRNA replacement therapy.…”