Department of Dermatology, The Affiliated Huaian NO.1 People's Hospital of Nanjing Medical University, No. 6, West Beijing Road, Huaiyin District, Huaian, 223300, Jiangsu, China.
Genes Genomics. 2021 May;43(5):491-501. doi: 10.1007/s13258-021-01074-3. Epub 2021 Mar 11.
Cutaneous squamous cell carcinoma (CSCC) is a severe malignancy derived from skin. Dysregulated circular RNAs (circRNAs) might play vital roles in tumor development.
Here, we aimed to explore the function of a novel circRNA circ_0067772 in CSCC.
Quantitative real-time PCR (qRT-PCR) or Western blot assay was performed to determine the expression of circ_0067772, microRNA (miR)-1238-3p and forkhead box protein G1 (FOXG1). Cell proliferation was assessed by Cell Counting Kit-8 (CCK-8) assay and colony formation assay. Transwell assay and wound healing assay were employed to examine cell metastasis. Flow cytometry was employed to monitor cell cycle and apoptosis. The target association between miR-1238-3p and circ_0067772 or FOXG1 was validated by dual-luciferase reporter assay. Moreover, role of circ_0067772 in vivo was investigated via xenograft model in nude mice.
Circ_0067772 and FOXG1 were upregulated, while miR-1238-3p was downregulated in CSCC tissues and cells. Circ_0067772 knockdown conferred inhibitory effects on cell proliferation, migration and invasion of CSCC cells. MiR-1238-3p served as a target of circ_0067772, whose silencing could reverse circ_0067772 knockdown-induced inhibitory impact on the malignant cellular behaviors. Circ_0067772 positively regulated FOXG1 expression by antagonizing miR-1238-3p. Additionally, miR-1238-3p could repress CSCC cell proliferation, migration and invasion by targeting FOXG1. Also, circ_0067772 knockdown hindered CSCC tumor growth in vivo.
Our study identified a novel oncogenic circRNA and the involvement of circ_0067772/miR-1238-3p/FOXG1 axis in CSCC development, providing a target for CSCC therapy.
皮肤鳞状细胞癌 (CSCC) 是一种严重的皮肤来源恶性肿瘤。失调的环状 RNA (circRNA) 可能在肿瘤发生中发挥重要作用。
本研究旨在探索新型环状 RNA circ_0067772 在 CSCC 中的功能。
采用实时定量 PCR (qRT-PCR) 或 Western blot 检测 circ_0067772、微小 RNA (miR)-1238-3p 和叉头框蛋白 G1 (FOXG1) 的表达。通过细胞计数试剂盒-8 (CCK-8) 检测和集落形成实验评估细胞增殖。Transwell 实验和划痕愈合实验用于检测细胞转移。流式细胞术用于监测细胞周期和凋亡。通过双荧光素酶报告实验验证 miR-1238-3p 与 circ_0067772 或 FOXG1 的靶基因关系。此外,通过裸鼠异种移植模型研究 circ_0067772 的体内作用。
CSCC 组织和细胞中 circ_0067772 和 FOXG1 上调,而 miR-1238-3p 下调。circ_0067772 下调可抑制 CSCC 细胞的增殖、迁移和侵袭。miR-1238-3p 是 circ_0067772 的靶基因,其沉默可逆转 circ_0067772 下调对恶性细胞行为的抑制作用。circ_0067772 通过拮抗 miR-1238-3p 正向调节 FOXG1 的表达。此外,miR-1238-3p 通过靶向 FOXG1 抑制 CSCC 细胞的增殖、迁移和侵袭。circ_0067772 下调还可抑制 CSCC 肿瘤在体内的生长。
本研究发现了一种新型致癌环状 RNA,以及 circ_0067772/miR-1238-3p/FOXG1 轴在 CSCC 发展中的作用,为 CSCC 治疗提供了一个新靶点。