Long non‑coding RNA FOXD2‑AS1/miR‑150‑5p/PFN2 axis regulates breast cancer malignancy and tumorigenesis

Jiang,Ming; Qiu,Ni; Xia,Haoming; Liang,Hongling; Li,Hongsheng; Ao,Xiang

doi:10.3892/ijo.2019.4671

Long non‑coding RNA FOXD2‑AS1/miR‑150‑5p/PFN2 axis regulates breast cancer malignancy and tumorigenesis

Authors:
- Ming Jiang
- Ni Qiu
- Haoming Xia
- Hongling Liang
- Hongsheng Li
- Xiang Ao
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Affiliations: Department of Breast Surgery, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, Guangdong 510095, P.R. China
Published online on: January 3, 2019 https://doi.org/10.3892/ijo.2019.4671
Pages: 1043-1052

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Abstract

Breast cancer (BC) is a common cancer and leading cause of cancer‑associated mortality in women. Abnormal expression of long non‑coding RNA FOXD2 adjacent opposite strand RNA 1 (FOXD2‑AS1) was associated with the development of a number of tumors. However, whether FOXD2‑AS1 is dysregulated in BC and its underlying mechanisms remain unclear. In the present study, it was identified that FOXD2‑AS1 expression was upregulated in BC tissue, cell lines and sphere subpopulation. Additionally, the abnormal upregulation of FOXD2‑AS1 predicted poor prognosis in patients with BC. Furthermore, downregulation of FOXD2‑AS1 decreased cell proliferation, and migratory and invasive abilities in BC cells, and decreased the growth of transplanted tumors in vivo. Downregulation of FOXD2‑AS1 decreased the percentage of CD44 antigen+/signal transducer CD24- in breast cancer stem cell (BCSC) cells, and decreased the expression of numerous stem factors, including Nanog, octamer‑binding transcription factor 4 (Oct4), and sex determining region Y‑box 2 (SOX2), and inhibited the epithelial‑mesenchymal transition process. FOXD2‑AS1 was identified to be primarily located in the cytoplasm. Using bioinformatics analysis, a reporter gene assay and reverse transcription‑polymerase chain reaction assays, it was demonstrated that microRNA (miR)‑150‑5p was able to bind directly with the 3'‑untranslated region of FOXD2‑AS1 and PFN2 mRNA. miR‑150‑5p mimics decreased the cell proliferation, migration and invasion of BC cells. FOXD2‑AS1 knockdown significantly inhibited the miR‑150‑5p inhibitor‑induced increase in Nanog, Oct4 and SOX2 expression. The miR‑150‑5p inhibitor‑induced increase in N‑cadherin, and decrease in E‑cadherin and vimentin was inhibited by FOXD2‑AS1 knockdown. Profilin 2 (PFN2) expression was significantly upregulated in BC tissues. Additionally, the abnormal upregulation of PFN2 was associated with poor prognosis in patients with BC. FOXD2‑AS1 and PFN2 expression was positively correlated. Collectively, the present results demonstrated the role of the FOXD2‑AS1/miR‑150‑5p/PFN2 axis in the development of BC, and provides novel targets for the treatment of BC, and potential biomarkers for diagnosis and prognosis of BC.

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