Overexpression of FER1L4 promotes the apoptosis and suppresses epithelial-mesenchymal transition and stemness markers via activating PI3K/AKT signaling pathway in osteosarcoma cells |
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| Affiliation: | 1. Department of Orthopaedics, Beijing Friendship Hospital, Capital Medical University, 100050, PR China;2. Department of Medicine, College of Medicine and Life Sciences, University of Toledo, Ohio, 43614, USA;1. Academy of Military Medical Sciences, Beijing, 100850, China;2. Department of Tumor Radiotherapy and Chemotherapy, Yinzhou People''s Hospital, Ningbo, 315040, China;1. Department of Orthopedics, Taizhou First People''s Hospital, Taizhou, 318020, Zhejiang, China;2. Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China;1. Department of VIP Unit, China-Japan Union Hospital of Jilin University, Changchun, 130033, China;2. Department of Orthopaedics, China-Japan Union Hospital of Jilin University, Changchun, 130033, China;3. Department of Neurosurgery, China-Japan Union Hospital of Jilin University, Changchun, 130033, China;4. Department of Ophthalmology, The First Affiliated Hospital of Jilin University, China;1. Department of Imaging Center, Northwest Women''s and Children''s Hospital, Xi''an, Shaanxi, 710061, China;2. Department of Imaging Center, The First Affiliated Hospital of Xi''an Jiao Tong University, Shaanxi, 710061, China;3. Department of Gynecology, Qingdao Women and Children''s Hospital, Qingdao, Shandong, 266000, China;4. Department of Imaging Department, Central Hospital of Hanzhong City, Shaanxi Province, Hanzhong, Shaanxi, 723000, China;1. Department of Orthopedics, Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China;2. Department of Anesthesia, Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China;1. Department of Emergency Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, PR China;2. Department of Orthopedics, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, PR China |
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| Abstract: | Novel long non-coding RNA Fer-1-like protein 4 (FER1L4) has been identified as a tumor suppressor in endometrial carcinoma, ovarian cancer, hepatocellular carcinoma, esophageal squamous cell carcinoma. However, the function of FER1L4 in osteosarcoma has not been clear. The aim of the research was to explore the effects of FER1L4 in osteosarcoma. Results showed that FER1L4 was observed to be lowly expressed in osteosarcoma cell lines (US-O2, MG-63 and SaOS-2 cells), especially MG63 cells. Besides, overexpression of FER1L4 remarkably repressed the proliferation, migration and invasion of MG63 cells. FER1L4-induced apoptotic cell death leaded to the activation of caspase-3 and Bax/Bcl2. Moreover, epithelial-mesenchymal transition (EMT) was tremendously suppressed by increased FER1L4, evidences were the increased E-cadherin and reduced vimentin and fibronectin. Blocking FER1L4 expression by sh-FER1L4 treatment increased the expression of SOX9, CD44, ALDH1, Nanog and Oct4, indicating that FER1L4 could effectively decrease cell stemness in osteosarcoma. Furthermore, the protein levels of p-AKT and p-PI3K were remarkably suppressed when FER1L4 was knocked down. In conclusion, the study indicated that FER1L4 acted as a tumor suppressor in osteosarcoma via activating PI3K/AKT pathway may be a new prognostic biomarker and potential therapeutic target for osteosarcoma intervention. |
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| Keywords: | FER1L4 Apoptosis EMT Stemness PI3K/AKT Osteosarcoma |
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