Yucheng Fu1, Qi Liu1, Qiyuan Bao1, Junxiang Wen1, Zhuochao Liu1, Yuehao Hu1, Guoyu He1, Cheng Peng1, Yiqi Xu1, Weibin Zhang2. 1. Department of Orthopedics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, PR China. 2. Department of Orthopedics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, PR China. zhangweibin10368@163.com.
Abstract
BACKGROUND: Osteosarcoma is the primary bone malignant neoplasm that often develops metastasis. Increasing evidences have shown that non-coding RNAs (ncRNAs) relate to the progression of osteosarcoma. However, the ncRNAs' roles in osteosarcoma metastasis are still unknown. METHODS: Differentially expressed (DE) RNAs were identified from Gene Expression Omnibus (GEO) database. Protein-protein interaction (PPI) of DE messenger RNAs (DEmRNAs) was built through STRING database. The target mRNAs and long ncRNAs (lncRNAs) of microRNAs (miRNA) were predicted through miRDB, Targetscan and Genecode databases, which then cross-checked with previously obtained DERNAs to construct competing endogenous RNA (ceRNA) network. All networks were visualized via Cytoscape and the hub RNAs were screened out through Cytoscape plug-in Cytohubba. The gene functional and pathway analyses were performed through DAVID and MirPath databases. The survival analyses of hub RNAs were obtained through Kaplan-Meier (KM) survival curves. RESULTS: Five hundred sixty-four DEmRNAs, 16 DElncRNAs and 22 DEmiRNAs were screened out. GO functional and KEGG pathway analyses showed that DERNAs were significantly associated with tumor metastasis. The ceRNA network including 6 lncRNAs, 55 mRNAs and 20 miRNAs were constructed and the top 10 hub RNAs were obtained. Above all, PI3K/AKT signaling pathway was identified as the most important osteosarcoma metastasis-associated pathway and its hub ceRNA module was constructed. The survival analyses showed that the RNAs in hub ceRNA module closely related to osteosarcoma patients' prognosis. CONCLUSIONS: The current study provided a new perspective on osteosarcoma metastasis. More importantly, the RNAs in hub ceRNA module might act as the novel therapeutic targets and prognostic factors for osteosarcoma patients.
BACKGROUND:Osteosarcoma is the primary bone malignant neoplasm that often develops metastasis. Increasing evidences have shown that non-coding RNAs (ncRNAs) relate to the progression of osteosarcoma. However, the ncRNAs' roles in osteosarcoma metastasis are still unknown. METHODS: Differentially expressed (DE) RNAs were identified from Gene Expression Omnibus (GEO) database. Protein-protein interaction (PPI) of DE messenger RNAs (DEmRNAs) was built through STRING database. The target mRNAs and long ncRNAs (lncRNAs) of microRNAs (miRNA) were predicted through miRDB, Targetscan and Genecode databases, which then cross-checked with previously obtained DERNAs to construct competing endogenous RNA (ceRNA) network. All networks were visualized via Cytoscape and the hub RNAs were screened out through Cytoscape plug-in Cytohubba. The gene functional and pathway analyses were performed through DAVID and MirPath databases. The survival analyses of hub RNAs were obtained through Kaplan-Meier (KM) survival curves. RESULTS: Five hundred sixty-four DEmRNAs, 16 DElncRNAs and 22 DEmiRNAs were screened out. GO functional and KEGG pathway analyses showed that DERNAs were significantly associated with tumor metastasis. The ceRNA network including 6 lncRNAs, 55 mRNAs and 20 miRNAs were constructed and the top 10 hub RNAs were obtained. Above all, PI3K/AKT signaling pathway was identified as the most important osteosarcoma metastasis-associated pathway and its hub ceRNA module was constructed. The survival analyses showed that the RNAs in hub ceRNA module closely related to osteosarcomapatients' prognosis. CONCLUSIONS: The current study provided a new perspective on osteosarcoma metastasis. More importantly, the RNAs in hub ceRNA module might act as the novel therapeutic targets and prognostic factors for osteosarcomapatients.
Authors: Ji Cao; Yijie Wang; Rong Dong; Guanyu Lin; Ning Zhang; Jing Wang; Nengming Lin; Yongchuan Gu; Ling Ding; Meidan Ying; Qiaojun He; Bo Yang Journal: Cancer Res Date: 2015-09-30 Impact factor: 12.701
Authors: Rajesha Rupaimoole; Jaehyuk Lee; Monika Haemmerle; Hui Ling; Rebecca A Previs; Sunila Pradeep; Sherry Y Wu; Cristina Ivan; Manuela Ferracin; Jennifer B Dennison; Niki M Zacharias Millward; Archana S Nagaraja; Kshipra M Gharpure; Michael McGuire; Nidhin Sam; Guillermo N Armaiz-Pena; Nouara C Sadaoui; Cristian Rodriguez-Aguayo; George A Calin; Ronny I Drapkin; Jeffery Kovacs; Gordon B Mills; Wei Zhang; Gabriel Lopez-Berestein; Pratip K Bhattacharya; Anil K Sood Journal: Cell Rep Date: 2015-12-10 Impact factor: 9.423