Yinling Mao1, Jiachen Lv2, Li Jiang3, Yihui Wang4. 1. Department of Abdominal Radiotherapy, Harbin Medical University Cancer Hospital, Harbin, 150001, Heilongjiang Province, China. 2. Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, NO. 150 Hapin Road, Harbin, 150001, Heilongjiang Province, China. 3. Department of Hemolymph, Harbin Medical University Cancer Hospital, Harbin, 150001, Heilongjiang Province, China. 4. Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, NO. 150 Hapin Road, Harbin, 150001, Heilongjiang Province, China. wangyihui8888@hotmail.com.
Abstract
BACKGROUND: Long non-coding RNAs (lncRNAs), acting as competing endogenous RNA (ceRNA) have been reported to regulate the expression of targeted genes by sponging miRNA in colon adenocarcinoma (COAD). METHODS: However, their potential implications for recurrence free survival prognosis and functional roles remains largely unclear in COAD. In this study, we downloaded the TCGA dataset (training dataset) and GSE39582 (validation dataset) of COAD patients with prognostic information. RESULTS: A total of 411 differentially expressed genes (DElncRNAs: 12 downregulated and 43 upregulated), 18 DE miRNAs (9 downregulated and 9 upregulated) and 338 DEmRNAs (113 downregulated and 225 upregulated) were identified in recurrence samples compared with non-recurrence samples with the thresholds of FDR < 0.05 and |log2FC|> 0.263. Based on six signature lncRNAs (LINC00899, LINC01503, PRKAG2-AS1, RAD21-AS1, SRRM2-AS1 and USP30-AS1), the risk score (RS) system was constructed. Two prognostic clinical features, including pathologic stage and RS model status were screened for building the nomogram survival model. Moreover, a recurrent-specific ceRNA network was successfully constructed with 2 signature lncRNAs, 4 miRNAs and 113 mRNAs. Furthermore, we further manifested that SRRM2-AS1 predicted a poor prognosis in COAD patients. Furthermore, knockdown of SRRM2-AS1 significantly suppressed cell proliferation, migration, invasion and EMT markers in HT-29 and SW1116 cells. CONCLUSION: These identified novel lncRNA signature and ceRNA network associated with recurrence prognosis might provide promising therapeutic targets for COAD patients.
BACKGROUND: Long non-coding RNAs (lncRNAs), acting as competing endogenous RNA (ceRNA) have been reported to regulate the expression of targeted genes by sponging miRNA in colon adenocarcinoma (COAD). METHODS: However, their potential implications for recurrence free survival prognosis and functional roles remains largely unclear in COAD. In this study, we downloaded the TCGA dataset (training dataset) and GSE39582 (validation dataset) of COADpatients with prognostic information. RESULTS: A total of 411 differentially expressed genes (DElncRNAs: 12 downregulated and 43 upregulated), 18 DE miRNAs (9 downregulated and 9 upregulated) and 338 DEmRNAs (113 downregulated and 225 upregulated) were identified in recurrence samples compared with non-recurrence samples with the thresholds of FDR < 0.05 and |log2FC|> 0.263. Based on six signature lncRNAs (LINC00899, LINC01503, PRKAG2-AS1, RAD21-AS1, SRRM2-AS1 and USP30-AS1), the risk score (RS) system was constructed. Two prognostic clinical features, including pathologic stage and RS model status were screened for building the nomogram survival model. Moreover, a recurrent-specific ceRNA network was successfully constructed with 2 signature lncRNAs, 4 miRNAs and 113 mRNAs. Furthermore, we further manifested that SRRM2-AS1 predicted a poor prognosis in COADpatients. Furthermore, knockdown of SRRM2-AS1 significantly suppressed cell proliferation, migration, invasion and EMT markers in HT-29 and SW1116 cells. CONCLUSION: These identified novel lncRNA signature and ceRNA network associated with recurrence prognosis might provide promising therapeutic targets for COADpatients.
Authors: Xiaohui Yan; Zhongyi Hu; Yi Feng; Xiaowen Hu; Jiao Yuan; Sihai D Zhao; Youyou Zhang; Lu Yang; Weiwei Shan; Qun He; Lingling Fan; Lana E Kandalaft; Janos L Tanyi; Chunsheng Li; Chao-Xing Yuan; Dongmei Zhang; Huiqing Yuan; Keqin Hua; Yiling Lu; Dionyssios Katsaros; Qihong Huang; Kathleen Montone; Yi Fan; George Coukos; Jeff Boyd; Anil K Sood; Timothy Rebbeck; Gordon B Mills; Chi V Dang; Lin Zhang Journal: Cancer Cell Date: 2015-10-12 Impact factor: 31.743
Authors: Carlo C Maley; Athena Aktipis; Trevor A Graham; Andrea Sottoriva; Amy M Boddy; Michalina Janiszewska; Ariosto S Silva; Marco Gerlinger; Yinyin Yuan; Kenneth J Pienta; Karen S Anderson; Robert Gatenby; Charles Swanton; David Posada; Chung-I Wu; Joshua D Schiffman; E Shelley Hwang; Kornelia Polyak; Alexander R A Anderson; Joel S Brown; Mel Greaves; Darryl Shibata Journal: Nat Rev Cancer Date: 2017-09-15 Impact factor: 60.716