Affiliations: Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
Correspondence:
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Corresponding author: Biao Wu, Department of General Surgery, The First Affiliated Hospital of Nanchang University, No. 17, Yongwaizheng Street, Donghu District, Nanchang, Jiangxi 330006, China. Tel.: +86 791 8869 3241; E-mail: hamingxinvknpu@163.com.
Abstract: Breast cancer is the most common malignancies worldwide. LncRNA HOX transcript antisense intergenic RNA (HOTAIR) has been shown to promote progression and metastasis of various cancers, including breast cancer. This reasearch aimed to investigate the downstream regulatory pathways of HOTAIR in breast cancer. The levels of HOTAIR and miR-129-5p were examined in breast cancer tissues and SKBR3 and MCF7 cells by quantitative real-time PCR (qRT-PCR). Cell proliferation was examined by Cell Counting Kit-8 (CCK-8) assay. Cell migration and invasion were estimated by transwell assay. Epithelial-to-mesenchymal transition (EMT)-related markers (E-cadherin, N-cadherin and Vimentin) were measured by Western blot assay. The expression of Frizzled 7 (FZD7) was detected using qRT-PCR or Western blot assay. Bioinformatics analysis, luciferase reporter assay or RNA Immunoprecipitation (RIP) assay was performed to explore the molecular mechanism of HOTAIR in breast cancer. Xenograft analysis was utilized to evaluate the tumor growth in vivo. HOTAIR and FZD7 were upregulated, while miR-129-5p was down-regulated in breast cancer tissues and cells. Knockdown of miR-129-5p reversed the effect of HOTAIR knockdown on cell proliferation, migration, invasion and EMT. FZD7 restored the inhibition of miR-129-5p on breast cancer progression. Furthermore, HOTAIR was a sponge of miR-129-5p and FZD7 was a target of miR-129-5p. Knockdown of HOTAIR inhibited the tumor growth in vivo. HOTAIR facilitated breast cancer progression by regulating the miR-129-5p/FZD7 axis, indicating that HOTAIR may be a potential biomarker and therapeutic target for breast cancer.
Keywords: HOTAIR, miR-129-5p, FZD7, breast cancer, progression
