Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
Department of Thoracic Surgery, Hebei Province Cangzhou Hospital of Integrated Traditional and Western Medicine, Hebei, China.
Thorac Cancer. 2022 Jun;13(12):1751-1762. doi: 10.1111/1759-7714.14450. Epub 2022 May 6.
Circular RNAs (circRNAs) can act as key regulators in human cancers, including esophageal squamous cell carcinoma (ESCC). However, the role and mechanism of circ_0005231 in ESCC have not previously been reported.
RNA levels and protein levels were detected by real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot assay, respectively. Cell proliferation was assessed by colony formation assay and 5-ethynyl-2'-deoxyuridine (EdU) assay. Wound healing and transwell assays were used to assess cell migration and invasion, respectively. The intermolecular interaction was predicted by bioinformatic analysis and verified by RNA immunoprecipitation (RIP), RNA pulldown and dual-luciferase reporter assays. Xenograft tumor model was used for exploring the biological function of circ_0005231 in vivo.
Circ_0005231 was upregulated in ESCC plasma, tissues and cells. Cell proliferation, migration and invasion were significantly restrained by knockdown of circ_0005231 in ESCC cells. Circ_0005231 acted as a sponge of miR-383-5p, and circ_0005231 regulated ESCC cellular behavior by sponging miR-383-5p. Moreover, miR-383-5p directly targeted KIAA0101, and circ_0005231 positively regulated KIAA0101 expression by sponging miR-383-5p. Furthermore, circ_0005231 knockdown suppressed the malignant behavior of ESCC cells by downregulating KIAA0101. Importantly, knockdown of circ_0005231 blocked xenograft tumor growth in vivo.
Circ_0005231 acted as a sponge of miR-383-5p to promote ESCC progression by upregulating KIAA0101, which provided a potential therapeutic strategy for ESCC treatment.
环状 RNA(circRNAs)可作为人类癌症(包括食管鳞状细胞癌[ESCC])的关键调节因子。然而,circ_0005231 在 ESCC 中的作用和机制尚未见报道。
采用实时定量聚合酶链反应(RT-qPCR)和 Western blot 检测 RNA 水平和蛋白水平。通过集落形成实验和 5-乙炔基-2'-脱氧尿苷(EdU)实验评估细胞增殖。采用划痕愈合和 Transwell 实验分别评估细胞迁移和侵袭。通过生物信息学分析预测分子间相互作用,并通过 RNA 免疫沉淀(RIP)、RNA 下拉和双荧光素酶报告基因实验进行验证。利用异种移植肿瘤模型在体内探索 circ_0005231 的生物学功能。
circ_0005231 在 ESCC 血浆、组织和细胞中上调。在 ESCC 细胞中,circ_0005231 的敲低显著抑制了细胞增殖、迁移和侵袭。circ_0005231 作为 miR-383-5p 的海绵,通过海绵 miR-383-5p 调节 ESCC 细胞行为。此外,miR-383-5p 直接靶向 KIAA0101,circ_0005231 通过海绵 miR-383-5p 正向调节 KIAA0101 表达。此外,circ_0005231 的敲低通过下调 KIAA0101 抑制 ESCC 细胞的恶性行为。重要的是,circ_0005231 的敲低在体内阻断了异种移植肿瘤的生长。
circ_0005231 作为 miR-383-5p 的海绵,通过上调 KIAA0101 促进 ESCC 进展,为 ESCC 的治疗提供了一种潜在的治疗策略。