Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Jilin, 130033, China.
Department of Nephrology, First Hospital of Jilin University, Jilin, 130021, China.
Cell Death Dis. 2021 May 15;12(5):499. doi: 10.1038/s41419-021-03756-y.
Long noncoding RNAs (lncRNAs) show emerging roles in colorectal cancer (CRC) development and are considered to be involved in the potential mechanism of tumor malignancy. While Sox2 overlapping transcript (SOX2OT) has been implicated in the progression of multiple cancers, its role in CRC remains to be explored. In this study, in situ hybridization (ISH) and qRT-PCR were performed to establish the functional relationships between SOX2OT and CRC deranged in CRC tissue and cells. Subsequently, SOX2OT shRNAs vectors were transfected into CRC cells to performed loss-of-function assays to detect the potential role of SOX2OT on proliferation and metastasis in vitro and vivo. The results showed SOX2OT was an oncogene that was up-regulated in human CRC tissues and cell lines. SOX2OT silencing suppressed cell proliferation, migration, and invasion in CRC cells in vitro, and inhibited tumorigenesis in the mouse xenografts. Bioinformatic predictive analysis coupled with the dual-luciferase reporter, RNA immunoprecipitation (RIP), and functional rescue assay elucidated the mechanistic network of the SOX2OT-miR-194-5p-SOX5 axis in CRC. Mechanistically, SOX2OT acted as a competing endogenous RNA (ceRNA) to upregulate SOX5 by sponging miR-194-5p. Downregulated SOX2OT boosted miR-194-5p expression, thus decreased the protein level of SOX5, which suppresses tumorgenesis of CRC.
长链非编码 RNA(lncRNA)在结直肠癌(CRC)的发展中表现出新兴的作用,被认为参与肿瘤恶性的潜在机制。虽然 Sox2 重叠转录物(SOX2OT)已被牵涉到多种癌症的进展中,但它在 CRC 中的作用仍有待探索。在这项研究中,通过原位杂交(ISH)和 qRT-PCR 来建立 SOX2OT 与 CRC 组织和细胞中失调的 CRC 之间的功能关系。随后,将 SOX2OT shRNA 载体转染到 CRC 细胞中进行功能丧失测定,以检测 SOX2OT 在体外和体内对增殖和转移的潜在作用。结果表明 SOX2OT 是一种在人 CRC 组织和细胞系中上调的癌基因。SOX2OT 沉默抑制了 CRC 细胞在体外的增殖、迁移和侵袭,并抑制了小鼠异种移植中的肿瘤发生。生物信息学预测分析结合双荧光素酶报告基因、RNA 免疫沉淀(RIP)和功能恢复测定阐明了 SOX2OT-miR-194-5p-SOX5 轴在 CRC 中的作用机制网络。从机制上讲,SOX2OT 作为竞争性内源性 RNA(ceRNA)通过海绵吸附 miR-194-5p 而上调 SOX5。下调的 SOX2OT 增加了 miR-194-5p 的表达,从而降低了 SOX5 的蛋白水平,抑制了 CRC 的肿瘤发生。