Background: SOX2 overlapping transcript (SOX2-OT) produces alternatively spliced long non-coding RNAs (lncRNA). Previous studies of the prognostic role of SOX2-OT expression met with conflicting results. The aim of this study was to properly consider the prognostic role of SOX2-OT expression in several cancers. In addition, the regulative mechanism of SOX2-OT is explored. Methods: PubMed, EMBASE, and Cochrane Library and The Cancer Genome Atlas (TCGA) database were comprehensively explored to recover pertinent studies. We conducted an extensive inquiry to verify the implication of SOX2-OT expression in cancer patients by conducting a meta-analysis of 13 selected studies. Thirty-two TCGA databases were used to analyze the connection between SOX2-OT expression and both the overall survival (OS) and clinicopathological characteristics of cancer patients using R and STATA 13.0. Trial sequential analysis (TSA) was adopted in order to compute the studies' power. Results: Thirteen studies involving 1172 cancer patients and 32 TCGA cancer types involving 9676 cancer patients were eventually selected. Elevated SOX2-OT expression was significantly related to shorter OS (HR = 2.026, 95% CI: 1.691-2.428, P < 0.0001) and disease-free survival (DFS) (HR = 2.554, 95% CI: 1.261-5.174, P = 0.0092) in cancer patients. Meanwhile, TSA substantiated adequate power to demonstrate the relationship between SOX2-OT expression and OS. The cancer patients with elevated SOX2-OT expression were more likely to have advanced clinical stage (RR = 1.468, 95% CI: 1.106-1.949, P = 0.0079), earlier lymphatic metastasis (P = 0.0005), earlier distant metastasis (P < 0.0001), greater tumor size (P < 0.0001), and more extreme tumor invasion (P < 0.0001) compared to those with low SOX2-OT expression. Meta-regression and
Colorectal cancer (CRC) is one of the leading causes of cancer‐related death worldwide. The existence of cancer stem cells (CSC) causes tumor relapses, metastasis, and resistance to conventional therapy. Alternative splicing has been shown to affect physiological and pathological processes. Accumulating evidence has confirmed that targeting alternative splicing could be an effective strategy to treat CRC. Currently, the role of alternative splicing in the regulation of CSC properties in CRC has not been elucidated. Here, we show that RBM17 displays oncogenic roles in CRC cells. RBM17 enhances cell proliferation and reduces chemotherapeutic‐induced apoptosis in CRC cells. Besides, RBM17 increases CD133 positive and ALDEFLUOR positive populations and promotes sphere formation in CRC cells. In mechanism studies, we found that FOXM1 is critical for RBM17 enhanced CSC properties. Moreover, FOXM1 alternative splicing is essential for RBM17 enhanced CSC properties in CRC cells. Additionally, RBM17 enhances CSC characteristics by controlling FOXM1 expression to promote Sox2 expression. Furthermore, AKT1 works as an upstream kinase to control RBM17‐mediated FOXM1 alternative splicing and enhancement of CSC properties in CRC cells. Our study reveals that AKT1‐RBM17‐FOXM1‐Sox2 axis could be a potential target for modulating alternative splicing to reduce CSC properties in CRC cells.
Background. Colorectal cancer (CRC) has been the 3rd most commonly malignant tumor of the gastrointestinal tract in the world. 5-Methylcytosine (m5C) and long noncoding RNAs (lncRNAs) have an essential role in predicting the prognosis and immune response for CRC patients. Therefore, we built a m5C-related lncRNA (m5CRlncRNA) model to investigate the prognosis and treatment methods for CRC patients. Methods. Firstly, we secured the transcriptome and clinical data for CRC from The Cancer Genome Atlas (TCGA). Then, m5CRlncRNAs were recognized by coexpression analysis. Then, univariate Cox, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses were utilized to build m5C-related prognostic characteristics. Besides, Kaplan-Meier analysis, ROC, PCA, C -index, enrichment analysis, and nomogram were performed to investigate the model. Additionally, immunotherapy responses and antitumor medicines were explored for CRC patients. Results. A total of 8 m5C-related lncRNAs (AC093157.1, LINC00513, AC025171.4, AC090948.2, ZEB1-AS1, AC109449.1, AC009041.3, and LINC02516) were adopted to construct a risk model to investigate survival and prognosis for CRC patients. CRC samples were separated into low- and high-risk groups, with the latter having a worse prognosis. The m5C-related lncRNA model helps us to better distinguish immunotherapy responses and IC50 of antitumor medicines in different groups of CRC patients. Conclusion. The research may give new perspectives on tailored therapy approaches as well as novel theories for forecasting the prognosis of CRC patients.
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