Background: Colorectal cancer (CRC) is a malignant cancer with a high mortality. Accumulating studies have revealed that mRNAs involved in ceRNA (competing endogenous RNA) network are implicated in the tumorigenesis and development of CRC. Here, we aimed to elucidate the ceRNA network involving Src kinase associated phosphoprotein 1 (SKAP1) in the biological characteristics of CRC. Methods: Expression levels of genes in colon adenocarcinoma (COAD) samples and prognosis of COAD patients were predicted using publicly available online tool. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), clony formation and Transwell assays were conducted to test the biological functions of SKAP1 and THUMPD3 antisense RNA 1 (THUMPD3-AS1) in CRC cells. Western blot was used to measure the protein levels of SKAP1. Gene expression in CRC cells was detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR). The interaction between miR-218-5p and THUMPD3-AS1 (or SKAP1) was verified by RNA pulldown and luciferase reporter assays. Results: SKAP1 was upregulated in COAD tissues and CRC cells and it reflected a poor prognosis in patients with COAD. SKAP1 knockdown inhibited CRC (HT-29 and HCT-116) cell proliferation, migration and invasion. Mechanistically, THUMPD3-AS1 acted as a ceRNA to sponge miR-218-5p and subsequently upregulated SKAP1 expression in CRC cells. SKAP1 overexpression reversed the suppressive effect of THUMPD3-AS1 knockdown on proliferation, migration and invision of CRC cells. Conclusions:THUMPD3-AS1 promotes CRC cell growth and aggressiveness by regulating the miR-218-5p/SKAP1 axis.

背景：结直肠癌（CRC）是一种死亡率较高的恶性肿瘤。越来越多的研究表明，参与 ceRNA（竞争性内源性 RNA）网络的 mRNA 与结直肠癌的肿瘤发生和发展有关。在这里，我们的目的是阐明 CRC 生物学特征中涉及 Src 激酶相关磷蛋白 1 (SKAP1) 的 ceRNA 网络。方法：使用公开的在线工具预测结肠腺癌（COAD）样本中基因的表达水平和 COAD 患者的预后。进行3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴化物(MTT)、克隆形成和Transwell实验来测试SKAP1和THUMPD3反义RNA 1 (THUMPD3-AS1)在结直肠癌中的生物学功能细胞。Western blot用于测量SKAP1的蛋白水平。通过逆转录定量聚合酶链反应（RT-qPCR）检测CRC细胞中的基因表达。通过 RNA Pulldown 和荧光素酶报告基因测定验证了 miR-218-5p 和 THUMPD3-AS1（或 SKAP1）之间的相互作用。结果：SKAP1在COAD组织和CRC细胞中表达上调，反映COAD患者预后不良。SKAP1 敲低抑制 CRC（HT-29 和 HCT-116）细胞增殖、迁移和侵袭。从机制上讲，THUMPD3-AS1 作为 ceRNA 海绵 miR-218-5p，随后上调 CRC 细胞中 SKAP1 的表达。SKAP1 过表达逆转了 THUMPD3-AS1 敲低对 CRC 细胞增殖、迁移和浸润的抑制作用。结论：THUMPD3-AS1通过调节miR-218-5p/SKAP1轴促进CRC细胞生长和侵袭性。