Circular RNAs (circRNAs), a novel type of endogenous noncoding RNAs, have been identified as critical regulators in human carcinogenesis. Here, we investigated the precise actions of hsa_circ_0009035 in the progression and radioresistance of cervical cancer (CC). The levels of hsa_circ_0009035, microRNA 889-3p (miR-889-3p), and homeobox B7 (HOXB7) were detected by quantitative real-time PCR (qRT-PCR) or Western blotting. RNase R and actinomycin D assays were used to assess the stability of hsa_circ_0009035. Cell proliferation, cell cycle progression, apoptosis, migration, and invasion were gauged with Cell Counting Kit-8 (CCK-8), flow cytometry, and transwell assays. Cell colony formation and survival were determined by the colony formation assay. Targeted correlations among hsa_circ_0009035, miR-889-3p, and HOXB7 were examined by the dual-luciferase reporter, RNA immunoprecipitation (RIP), or RNA pulldown assay. Animal studies were performed to evaluate the impact of hsa_circ_0009035 on tumor growth. We found that hsa_circ_0009035 was highly expressed in CC tissues and cells, and it was associated with the radioresistance of CC patients. Moreover, the silencing of hsa_circ_0009035 inhibited CC cell proliferation, migration, invasion, and it enhanced apoptosis and radiosensitivity in vitro and weakened tumor growth in vivo. Mechanistically, hsa_circ_0009035 directly targeted miR-889-3p by binding to miR-889-3p, and hsa_circ_0009035 modulated HOXB7 expression through miR-889-3p. HOXB7 was a functional target of miR-889-3p in regulating CC progression and radioresistance in vitro, and hsa_circ_0009035 modulated CC progression and radioresistance in vitro by miR-889-3p. Our current study first identified hsa_circ_0009035 as an important regulator of CC progression and radioresistance at least in part through targeting the miR-889-3p/HOXB7 axis, highlighting its significance as a potential therapeutic target for CC treatment.

中文翻译：

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hsa_circ_0009035 的沉默通过 HOXB7 的 MicroRNA 889-3p 依赖性调节抑制宫颈癌进展并增强放射敏感性

环状 RNA (circRNAs) 是一种新型的内源性非编码 RNA，已被确定为人类致癌作用的关键调节因子。在这里，我们研究了 hsa_circ_0009035 在宫颈癌 (CC) 进展和放射抗性中的精确作用。通过实时定量 PCR (qRT-PCR) 或蛋白质印迹法检测 hsa_circ_0009035、microRNA 889-3p (miR-889-3p) 和同源框 B7 (HOXB7) 的水平。RNase R 和放线菌素 D 测定用于评估 hsa_circ_0009035 的稳定性。细胞增殖、细胞周期进程、细胞凋亡、迁移和侵袭使用细胞计数试剂盒-8 (CCK-8)、流式细胞术和 transwell 测定进行测量。细胞集落形成和存活通过集落形成试验确定。hsa_circ_0009035、miR-889-3p、和 HOXB7 通过双荧光素酶报告基因、RNA 免疫沉淀 (RIP) 或 RNA pulldown 测定进行检查。进行动物研究以评估 hsa_circ_0009035 对肿瘤生长的影响。我们发现hsa_circ_0009035在CC组织和细胞中高表达，并且与CC患者的放射抗性有关。此外，hsa_circ_0009035的沉默抑制了CC细胞的增殖、迁移、侵袭，并增强了细胞凋亡和放射敏感性体外和体内减弱肿瘤生长。从机制上讲，hsa_circ_0009035 通过与 miR-889-3p 结合直接靶向 miR-889-3p，而 hsa_circ_0009035 通过 miR-889-3p 调节 HOXB7 表达。HOXB7 是 miR-889-3p 在体外调节 CC 进展和放射抗性的功能靶点，hsa_circ_0009035通过 miR-889-3p在体外调节 CC 进展和放射抗性。我们目前的研究首先确定 hsa_circ_0009035 是 CC 进展和放射抗性的重要调节因子，至少部分是通过靶向 miR-889-3p/HOXB7 轴，突出了其作为 CC 治疗潜在治疗靶点的重要性。