The First School of Clinical Medicine, Southern Medical University, No. 1023 shatai south Road, Baiyun District, Guangzhou, Guangdong, 510080, China; Department of Gastroenterology, Affiliated PingXiang Hospital, Southern Medical University, No. 8, Wugong Mountain Avenue, Development Zone, Pingxiang, Jiangxi, 337055, China.
Department of Critical Care Medicine, The First Affiliated Hospital of Fujian Medical University, No.20 Chazhong Road, Taijiang District, Fuzhou, Fujian, 350005, China.
Biochem Biophys Res Commun. 2019 Apr 2;511(2):239-245. doi: 10.1016/j.bbrc.2019.02.006. Epub 2019 Feb 22.
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.
结直肠癌（CRC）是一种常见的恶性肿瘤，具有高发病率和死亡率。由于诊断较晚，大多数 CRC 患者错过了根治性手术的最佳时机，导致 CRC 死亡率较高。因此，确定新的预后和治疗靶点非常重要。长链非编码 RNA 被认为是肿瘤进展的重要调节因子，包括 CRC。已有研究表明，LncRNA SUMO1P3 是促进多种癌症增殖、细胞周期和转移的癌基因，但它在 CRC 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 CRC 中的上调及其预后意义。功能丧失实验表明，SUMO1P3 可促进 CRC 细胞的增殖能力，并抑制其凋亡能力。细胞质多聚腺苷酸化元件结合蛋白 3（CPEB3）在多种癌症中被新认为是一种肿瘤抑制基因，并被发现在 CRC 中低表达。我们通过 UCSC 数据库预测，并通过 ChIP 实验验证，组蛋白 H3 赖氨酸 27 三甲基化（H3K27me3）的关键调节因子 EZH2 结合到 CPEB3 启动子上。进一步验证表明，SUMO1P3 通过 EZH2 对 CPEB3 进行表观遗传抑制。最后，挽救实验表明，SUMO1P3 通过 CPEB3 促进 CRC 细胞的增殖、细胞周期和抑制凋亡。因此，本研究表明，lncRNA SUMO1P3 通过表观遗传沉默 CPEB3 促进 CRC 细胞的增殖能力并抑制其凋亡能力，为 CRC 患者提供了一种新的预后标志物。
