LncRNA CFRL aggravates cardiac fibrosis by modulating both miR-3113-5p/CTGF and miR-3473d/FN1 axis
Yue Cui,
Bozhong Shi,
Zijie Zhou,
Bo Chen,
Xiaoyang Zhang,
Cong Li,
Kai Luo,
Zhongqun Zhu,
Jinghao Zheng,
Xiaomin He
Affiliations
Yue Cui
Department of Cardiothoracic Surgery, Shanghai Children’s Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine, 1678 Dongfang Road, Shanghai 200127, China
Bozhong Shi
Department of Cardiothoracic Surgery, Shanghai Children’s Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine, 1678 Dongfang Road, Shanghai 200127, China
Zijie Zhou
Department of Cardiothoracic Surgery, Shanghai Children’s Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine, 1678 Dongfang Road, Shanghai 200127, China
Bo Chen
Department of Cardiothoracic Surgery, Shanghai Children’s Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine, 1678 Dongfang Road, Shanghai 200127, China
Xiaoyang Zhang
Department of Cardiothoracic Surgery, Shanghai Children’s Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine, 1678 Dongfang Road, Shanghai 200127, China
Cong Li
Department of Cardiothoracic Surgery, Shanghai Children’s Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine, 1678 Dongfang Road, Shanghai 200127, China
Kai Luo
Department of Cardiothoracic Surgery, Shanghai Children’s Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine, 1678 Dongfang Road, Shanghai 200127, China
Zhongqun Zhu
Department of Cardiothoracic Surgery, Shanghai Children’s Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine, 1678 Dongfang Road, Shanghai 200127, China
Jinghao Zheng
Department of Cardiothoracic Surgery, Shanghai Children’s Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine, 1678 Dongfang Road, Shanghai 200127, China; Corresponding author
Xiaomin He
Department of Cardiothoracic Surgery, Shanghai Children’s Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine, 1678 Dongfang Road, Shanghai 200127, China; Corresponding author
Summary: Cardiac fibrosis is a major type of adverse remodeling, predisposing the disease progression to ultimate heart failure. However, the complexity of pathogenesis has hampered the development of therapies. One of the key mechanisms of cardiac diseases has recently been identified as long non-coding RNA (lncRNA) dysregulation. Through in vitro and in vivo studies, we identified an lncRNA NONMMUT067673.2, which is named as a cardiac fibrosis related lncRNA (CFRL). CFRL was significantly increased in both mouse model and cell model of cardiac fibrosis. In vitro, CFRL was proved to promote the proliferation and migration of cardiac fibroblasts by competitively binding miR-3113-5p and miR-3473d and indirectly up-regulating both CTGF and FN1. In vivo, silencing CFRL significantly mitigated cardiac fibrosis and improved left ventricular function. In short, CFRL may exert an essential role in cardiac fibrosis and interfering with CFRL might be considered as a multitarget strategy for cardiac fibrosis and heart failure.
