miR‑124 targets retinoid X receptor α to reduce growth of TSC2‑deficient lymphangioleiomyomatosis

Liu,Jia; Yuan,Jun; Feng,Tianxiang; Zhao,Yinjuan; Sun,Qian; Chen,Jun; Chen,Jingyu; Jin,Meiling; Xue,Bin

doi:10.3892/or.2018.6916

miR‑124 targets retinoid X receptor α to reduce growth of TSC2‑deficient lymphangioleiomyomatosis

Authors:
- Jia Liu
- Jun Yuan
- Tianxiang Feng
- Yinjuan Zhao
- Qian Sun
- Jun Chen
- Jingyu Chen
- Meiling Jin
- Bin Xue
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Affiliations: MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing, Jiangsu 210093, P.R. China, Biochemical and Environmental Engineering School of Xiaozhuang Collage, Nanjing, Jiangsu 211171, P.R. China, Jiangsu Key Laboratory of Molecular Medicine, School of Medicine, Nanjing University, Nanjing, Jiangsu 210093, P.R. China, Collaborative Innovation Center of Sustainable Forestry in Southern China, College of Forestry, Nanjing Forestry University, Nanjing, Jiangsu 210037, P.R. China, Department of Pathology, The Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210008, P.R. China, Department of Cardiothoracic Surgery, Lung Transplant Group, Wuxi People's Hospital, Nanjing Medical University, Wuxi, Jiangsu 214023, P.R. China , Pulmonary Department, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China
Published online on: December 7, 2018 https://doi.org/10.3892/or.2018.6916
Pages: 1342-1350

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Abstract

Lymphangioleiomyomatosis (LAM) is a rare neoplastic disease that leads to progressive destruction of lung function. However, the mechanisms underlying the progression of LAM remain unknown. Recent studies demonstrated that miR‑124‑3p (hereinafter referred to as miR‑124) is a downregulated miRNA in tumors and it is still unclear whether miR‑124 participates in LAM. In the present study, it was revealed that miR‑124 was downregulated in LAM specimens and overexpression of miR‑124 resulted in the apoptosis of TSC2‑deficient cells via RXRα (retinoid X receptor α), while slightly influencing TSC2 wild‑type cells. Furthermore, a xenograft model demonstrated that the miR‑124/RXRα axis regulated the growth and fatty acid oxidation genes in TSC2‑null cells. Altogether, our results revealed the suppressive functions and mechanisms of miR‑124 in LAM progression, providing novel therapeutic targets for LAM treatment.

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