Nanjing Medical University, Nanjing 210000, Jiangsu, China; Wuxi People's Hospital, Wuxi 214000, Jiangsu, China.
Wuxi People's Hospital, Wuxi 214000, Jiangsu, China.
Dig Liver Dis. 2020 Dec;52(12):1494-1502. doi: 10.1016/j.dld.2020.07.019. Epub 2020 Aug 15.
Circular RNAs are crucial in tumorigenesis. However, little is known about their functions in colorectal cancer (CRC). Circ-SMARCA5 was found to be an oncogene or tumor suppresser in different types of cancers, but its exact role in CRC remains unknown. Here, we aim to identify the role of circ-SMARCA5 in CRC development.
Circ-SMARCA5 expression was determined by qRT-PCR. CRC cell proliferation, migration, and invasion were detected by CCK-8, wound healing, and Transwell assays, respectively. Bioinformatics analysis was performed to predict target genes. The interaction of microRNA (miR) with circ-SMARCA5 or target genes was detected using luciferase reporter assay. Xenograft model was established to determine the effect of circ-SMARCA5 on CRC tumor growth in vivo.
Circ-SMARCA5 expression was dramatically decreased in CRC cell lines and tissues. Circ-SMARCA5 overexpression inhibited CRC cell proliferation, migration and invasion. MiR-93-3p was predicted as a target of circ-SMARCA5 and its overexpression attenuated the anti-tumor effect of circ-SMARCA5 on CRC cells. Furthermore, we predicted AT-rich interaction domain 4B (ARID4B) as the target of miR-39-3p. Functional analysis showed that circ-SMARCA5 upregulated ARID4B expression via miR-39-3p. Additionally, in vivo studies demonstrated that circ-SMARCA5 suppressed CRC tumor progression.
Circ-SMARCA5 functions as a tumor suppressor by upregulating ARID4B expression via sponging miR-39-3p, and thereby inhibited CRC progression.
环状 RNA 在肿瘤发生中起着至关重要的作用。然而,它们在结直肠癌(CRC)中的功能知之甚少。Circ-SMARCA5 在不同类型的癌症中被发现是癌基因或肿瘤抑制因子,但它在 CRC 中的确切作用仍不清楚。在这里,我们旨在确定 circ-SMARCA5 在 CRC 发展中的作用。
通过 qRT-PCR 测定 circ-SMARCA5 的表达。通过 CCK-8、划痕愈合和 Transwell 测定分别检测 CRC 细胞的增殖、迁移和侵袭。进行生物信息学分析以预测靶基因。使用荧光素酶报告基因测定检测 microRNA(miR)与 circ-SMARCA5 或靶基因的相互作用。建立异种移植模型以确定 circ-SMARCA5 对 CRC 肿瘤在体内生长的影响。
Circ-SMARCA5 的表达在 CRC 细胞系和组织中明显降低。Circ-SMARCA5 的过表达抑制 CRC 细胞的增殖、迁移和侵袭。MiR-93-3p 被预测为 circ-SMARCA5 的靶基因,其过表达减弱了 circ-SMARCA5 对 CRC 细胞的抗肿瘤作用。此外,我们预测富含 AT 的相互作用域 4B(ARID4B)是 miR-39-3p 的靶基因。功能分析表明,circ-SMARCA5 通过 miR-39-3p 上调 ARID4B 的表达。此外,体内研究表明,circ-SMARCA5 抑制 CRC 肿瘤的进展。
Circ-SMARCA5 通过海绵吸附 miR-39-3p 上调 ARID4B 的表达,从而发挥肿瘤抑制作用,抑制 CRC 的进展。