Long non‑coding RNA FOXD2‑AS1/miR‑150‑5p/PFN2 axis regulates breast cancer malignancy and tumorigenesis.
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.
['Jiang|Ming|M|', 'Qiu|Ni|N|', 'Xia|Haoming|H|', 'Liang|Hongling|H|', 'Li|Hongsheng|H|', 'Ao|Xiang|X|']
D020413:3' Untranslated Regions D000818:Animals D001943:Breast Neoplasms D063646:Carcinogenesis D045744:Cell Line, Tumor D002465:Cell Movement D049109:Cell Proliferation D002471:Cell Transformation, Neoplastic D003593:Cytoplasm D058750:Epithelial-Mesenchymal Transition D005260:Female D015972:Gene Expression Regulation, Neoplastic D006801:Humans D018960:Hyaluronan Receptors D051379:Mice D035683:MicroRNAs D051304:Profilins D011379:Prognosis D062085:RNA, Long Noncoding D012333:RNA, Messenger D014407:Tumor Cells, Cultured
breast cancer tumorigenesis long non-coding RNA FOXD2 adjacent opposite strand RNA 1 microRNA150-5p profilin 2