LncRNA SUMO1P3 promotes proliferation and inhibits apoptosis in colorectal cancer by epigenetically silencing CPEB3
LncRNA SUMO1P3 promotes proliferation and inhibits apoptosis in colorectal cancer by epigenetically silencing CPEB3
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DOI：
10.1016/j.bbrc.2019.02.006
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发表时间：
2019-04-02
影响因子：
3.1
通讯作者：
Wen, Jianbo
中科院分区：
文献类型：
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作者：
Lin, Hao;Guo, Qingqing;Wen, Jianbo
结直肠癌(CRC)是一种发病率高、死亡率高的常见恶性肿瘤。由于诊断较晚，大多数结直肠癌患者错过了合适的根治性手术时机，导致结直肠癌死亡率较高。因此，确定新的预后和治疗靶点是重要的。长的非编码RNA被报道为肿瘤进展的重要调节因子，包括在结直肠癌中。LncRNA SUMO1P3是一种在多种癌症中促进增殖、细胞周期和转移的癌基因，但其在结直肠癌中的作用尚未被揭示。本研究旨在探讨SUMO1P3在结直肠癌中的作用及其机制。我们验证了SUMO1P3在结直肠癌中的表达上调及其预后意义。功能丧失分析表明，SUMO1P3可促进结直肠癌细胞的增殖，抑制细胞的凋亡。胞浆多聚腺苷酸化元件结合蛋白3(CPEB3)是近年来发现的一种肿瘤抑制基因，在结直肠癌中低表达。我们通过UCSC数据库预测了组蛋白H3赖氨酸27位三甲基化的关键调控因子EZH2(H3K27me3)与CPEB3启动子结合。此外，我们验证了SUMO1P3通过EZH2在表观遗传上抑制了CPEB3。补救实验表明，SUMO1P3通过CPEB3促进细胞增殖、细胞周期和抑制细胞凋亡。因此，目前的研究表明，LncRNA SUMO1P3通过在表观上沉默CPEB3而促进结直肠癌细胞的增殖和抑制细胞的凋亡，为结直肠癌患者提供了一种新的预后指标。(C)2019 Elsevier Inc.保留所有权利。
Colorectal cancer (CRC) is a prevalent malignancy characterized with high morbidity and death rate. Due to late diagnosis, most CRC patients missed the proper timing for radical operation, which led to the high mortality in CRC. Therefore, identifying new prognostic and therapeutic targets is important. Long non-coding RNAs are reported as essential regulators for tumor progression, including in CRC. LncRNA SUMO1P3 has been documented as an oncogene promoting proliferation, cell cycle, and metastasis in several cancers, but its role in CRC has never been unveiled. The purpose of our study is to interrogate the functions and mechanism of SUMO1P3 in colorectal cancer. We validated the upregulation and the prognostic significance of SUMO1P3 in CRC. The loss-of-function assays suggested that SUMO1P3 provoked CRC cell proliferative ability, and retarded apoptotic ability. Cytoplasmic polyadenylation element binding protein 3 (CPEB3) has been newly acknowledged as a tumor suppressive gene in several cancers, and has been revealed to present low expression in CRC. We predicted through UCSC database and validated by ChIP assay that EZH2, a crucial regulator of trimethylation of histone H3 at lysine 27 (H3K27me3), bound to CPEB3 promoter. Further, we validated that SUMO1P3 epigenetically repressed CPEB3 through EZH2. Finally, rescue assays indicated that SUMO1P3 provoked proliferation, cell cycle, and retarded apoptosis through CPEB3.Consequently, current study showed that lncRNA SUMO1P3 promoted cell proliferative ability and inhibited apoptotic ability in CRC by epigenetically silencing CPEB3, providing a novel prognostic marker for CRC patients. (C) 2019 Elsevier Inc. All rights reserved.