Department of Gynecology, the First Affiliated Hospital of Jinan University.
Department of Gynecology, Panyu Central Hospital.
Anticancer Drugs. 2023 Jun 1;34(5):659-668. doi: 10.1097/CAD.0000000000001435. Epub 2022 Dec 19.
Cervical cancer is one of the most common malignant tumors in women. Circular RNA (circRNA) has been shown to play a crucial role in cervical cancer. Here, the aim of this study was to explore the functions and a novel miRNA/mRNA network underlying circ_0000212 in cervical cancer regulation. The expression of circ_000212, miR-625-5p and Protein Tyrosine Phosphatase 4A1 (PTP4A1) mRNA was measured by quantitative real-time PCR (qRT-PCR). 5-ethynyl-2'-deoxyuridine assay was conducted to detect the proliferation of cervical cancer cells. Wound healing and transwell assays were employed to assess cell migration and invasion. The angiogenesis abilities of cervical cancer cells were evaluated by tube formation assay. Flow cytometry was performed for analyzing cell apoptosis. The expression of PTP4A1 protein and apoptosis-relative protein were detected via western blot. The dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were employed to clarify the interaction between circ_0000212 or PTP4A1 and miR-625-5p. The impact of circ_0000212 on cervical cancer growth in vivo was detected by xenograft assay. Circ_0000212 and PTP4A1 were highly expressed and miR-625-5p expression level was decreased in cervical cancer. Circ_0000212 silencing suppressed cervical cancer cell proliferation, migration, invasion and angiogenesis while promoting apoptosis. MiR-625-5p was targeted by circ_0000212, and miR-625-5p inhibition reversed the effects of circ_0000212 knockdown. MiR-625-5p directly targeted PTP4A1, and the inhibitory effect of miR-625-5p on the malignant progression of cervical cancer was reversed after PTP4A1 overexpression. In-vivo assays validated that circ_0000212 promoted cervical cancer tumor growth in vivo . circ_0000212 acted as an oncogene in cervical cancer progression, and knockdown of circ_0000212 repressed cervical cancer development by increasing miR-625-5p and decreasing PTP4A1.
宫颈癌是女性最常见的恶性肿瘤之一。环状 RNA(circRNA)已被证明在宫颈癌中发挥关键作用。本研究旨在探讨 circ_0000212 在宫颈癌调控中的作用及其新型 miRNA/mRNA 网络。通过实时定量 PCR(qRT-PCR)测量 circ_000212、miR-625-5p 和 Protein Tyrosine Phosphatase 4A1(PTP4A1)mRNA 的表达。5-乙炔基-2'-脱氧尿苷检测用于检测宫颈癌细胞的增殖。划痕愈合和 Transwell 实验用于评估细胞迁移和侵袭。管形成实验评估宫颈癌细胞的血管生成能力。流式细胞术用于分析细胞凋亡。Western blot 检测 PTP4A1 蛋白和凋亡相关蛋白的表达。双荧光素酶报告和 RNA 免疫沉淀(RIP)实验用于阐明 circ_0000212 或 PTP4A1 与 miR-625-5p 的相互作用。通过异种移植实验检测 circ_0000212 对宫颈癌体内生长的影响。Circ_0000212 和 PTP4A1 表达上调,miR-625-5p 表达下调在宫颈癌中。Circ_0000212 沉默抑制宫颈癌细胞增殖、迁移、侵袭和血管生成,促进细胞凋亡。Circ_0000212 靶向 miR-625-5p,抑制 circ_0000212 敲低后可逆转 miR-625-5p 的抑制作用。miR-625-5p 直接靶向 PTP4A1,过表达 PTP4A1 后可逆转 miR-625-5p 对宫颈癌恶性进展的抑制作用。体内实验验证 circ_0000212 促进宫颈癌肿瘤在体内生长。circ_0000212 在宫颈癌进展中起癌基因作用,通过增加 miR-625-5p 和降低 PTP4A1 来抑制 circ_0000212 敲低可抑制宫颈癌的发展。