Abstract
BackgroundLong 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).MethodsHowever, 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.ResultsA 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.ConclusionThese identified novel lncRNA signature and ceRNA network associated with recurrence prognosis might provide promising therapeutic targets for COAD patients.
Highlights
Long non-coding RNAs, acting as competing endogenous RNA have been reported to regulate the expression of targeted genes by sponging miRNA in colon adenocarcinoma (COAD)
Based on the screening criteria of |log2FC|> 0.263 and False discovery rate (FDR) < 0.05, differentially expressed RNAs (DERs), including 18 DEmiRNAs (9 up-regulated and 9 downregulated), 338 DEmRNAs (225 up-regulated and 113 down-regulated) and 55 DElncRNAs (43 up-regulated and 12 down-regulated) were identified in recurrence samples compared with non-recurrence samples (Additional file 1: Table S1)
Volcano plot and bidirectional hierarchical clustering heatmap were described to the DEmiRNAs (Fig. 1A), DEmRNAs and DElncRNAs (Fig. 1B), which clearly indicated the samples tend to cluster in two distinct directions
Summary
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). Accumulating evidence has confirmed the oncogenic or tumor suppressive role of lncRNAs in colon cancer development. LncRNA CASC15 promotes colon cancer cell proliferation and metastasis by regulating the miR‐4310/ LGR5/Wnt/β‐catenin signaling pathway [12]. LncRNA B3GALT5-AS1 suppressed colon cancer liver metastasis via its binding on miR-203 promoter and the repression of miR-203 [13]. As reported by Fu et al [14], a seven-lncRNA signature associated with prognosis of COAD was identified and validated by different cohorts. Lin et al [15] developed an immune-related nine-lncRNA signature predictive of overall survival in colon cancer. The research focused on functional lncRNAs associated with independent recurrent prognosis still remain relatively little
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
