Long non‑coding RNA FOXD2‑AS1 regulates the tumorigenesis and progression of breast cancer via the S100 calcium binding protein A1/Hippo signaling pathway

Huang,Pei; Xue,Jinhui

doi:10.3892/ijmm.2020.4699

Long non‑coding RNA FOXD2‑AS1 regulates the tumorigenesis and progression of breast cancer via the S100 calcium binding protein A1/Hippo signaling pathway

Authors:
- Pei Huang
- Jinhui Xue
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Affiliations: Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China, Department of Pathology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, Henan 450000, P.R. China
Published online on: August 10, 2020 https://doi.org/10.3892/ijmm.2020.4699
Pages: 1477-1489
Copyright: © Huang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Breast cancer is one of the most prevalent cancer types and is accompanied by a high incidence and mortality rate, severely threatening women's health globally. Long non‑coding RNA forkhead box D2 adjacent apposite strand RNA 1 (lncRNA FOXD2‑AS1) has been identified to function as an oncogene in human cancers; however, it has rarely been investigated in breast cancer. The aim of the present study was to investigate the role of FOXD2‑AS1 in breast cancer, and to clarify the underlying mechanisms. The expression of FOXD2‑AS1 in breast cancer cell lines was first quantified by reverse transcription‑quantitative PCR, and the biological function of FOXD2‑AS1 was then determined. Cellular proliferative ability was determined by Cell Counting kit‑8 assay, and wound healing and Transwell assays were conducted to assess the cell migratory and invasive ability. Corresponding protein expression levels were determined by western blot analysis. In addition, experimental animal models were established by the subcutaneous injection of MDA‑MB‑468 cells into the right axillary lymph nodes of BALB/c nude mice, and the effects of FOXD2‑AS1 on tumor growth were observed. The results indicated that FOXD2‑AS1 expression was upregulated in breast cancer cell lines, and that FOXD2‑AS1 downregulation significantly inhibited the proliferation, migration and invasiveness of MCF‑7 and MDA‑MB‑468 cells. S100 calcium binding protein A1 (S100A1) was also upregulated in breast cancer cell lines and was positively regulated by FOXD2‑AS1. Furthermore, the inhibition of S100A1 and the overexpression of the serine/threonine‑protein kinase, large tumor suppressor homolog 1 (LATS1), inhibited the FOXD2‑AS1‑induced cellular proliferation, migration and invasiveness in breast cancer. Experimental mouse models revealed that FOXD2‑AS1 downregulation significantly inhibited tumor growth, and that the levels of phosphorylated (p‑)YAP and p‑LATS1 were upregulated by FOXD2‑AS1 knockdown, indicating that the inhibition of FOXD2‑AS1 activated Hippo/yes‑associated protein signaling. On the whole, the findings of the present study suggest that the FOXD2‑AS1/S100A1/Hippo axis is involved in the tumorigenesis and progression of breast cancer. In the future, these may contribution to the identification of more effective breast cancer treatments.

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