Long noncoding RNA homeobox A11 antisense promotes transforming growth factor β1‑induced fibrogenesis in cardiac fibroblasts

Wang,Jiangting; Liu,Xiaowei; Zhuang,Qin; Pan,Rongrong; Zou,Linlin; Cen,Zhenbo; Tang,Lijiang

doi:10.3892/mmr.2019.9891

Long noncoding RNA homeobox A11 antisense promotes transforming growth factor β1‑induced fibrogenesis in cardiac fibroblasts

Authors:
- Jiangting Wang
- Xiaowei Liu
- Qin Zhuang
- Rongrong Pan
- Linlin Zou
- Zhenbo Cen
- Lijiang Tang
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Affiliations: Department of Cardiology, Zhejiang Hospital, Hangzhou, Zhejiang 310013, P.R. China, Department of Cardiology, Cixi People's Hospital, Wenzhou Medical University, Cixi, Zhejiang 315300, P.R. China
Published online on: January 24, 2019 https://doi.org/10.3892/mmr.2019.9891
Pages: 2817-2824

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Abstract

Cardiac fibrosis is closely associated with various heart diseases and is an important pathological feature of cardiac remodeling. However, detailed mechanisms underlying cardiac fibrosis remain largely unknown. Long noncoding RNAs (lncRNAs) are reported to serve significant roles in the development of cardiac fibrosis. The present study aimed to identify the role of a novel lncRNA, homeobox A11 antisense (HOXA11‑AS), in cardiac fibrosis. Overexpression of HOXA11‑AS in mouse cardiac fibroblasts (CFs) increased the expression of transforming growth factor β1 (TGFβ1) and its downstream molecules, while knockdown of HOXA11‑AS inhibited the TGFβ1 signaling pathway. Furthermore, as determined by colony formation and MTT assays, HOXA11‑AS overexpression promoted colony formation and viability in mouse CFs, while HOXA11‑AS knockdown had the opposite effect. In addition, overexpression of HOXA11‑AS increased cell migration and invasion in the Transwell assays, whereas expression knockdown decreased the metastatic ability of cells. In order to explore the detailed mechanism, co‑transfection of HOXA11‑AS expression plasmid and siTGFβ1 into CFs resulted in increased cell proliferative rate and cell metastasis through the TGFβ1 signaling pathway. Taken together, the present study suggested that the lncRNA HOXA11‑AS may be a potential therapeutic target against cardiac fibrosis, and provided a novel insight into the diagnosis and treatment of clinical cardiac fibrosis.

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