Ye Xia, Zhu Biqing, Han Jingjing, Huang Jian, Wu Yaqin
Department of Radiation Oncology, The First People's Hospital of Nantong, The Second Affiliated Hospital of Nantong University, Nantong 226001, China.
Department of Radiation Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing 210009, China.
J Genomics. 2022 Jan 11;10:16-25. doi: 10.7150/jgen.62458. eCollection 2022.
: Cervical cancer (CC) is one of the most common female malignancies worldwide. An increasing body of evidence suggests that circular RNAs (circRNAs) participate in the pathogenesis of various cancers, including CC. However, the expression profile and underlying molecular mechanisms remain largely unknown. : In this study, high throughput sequencing was applied to identify circRNA in HPV-16 positive CC tissues. Quantitative real-time PCR (qRT-PCR) was performed to validate the expression in CC tissues and cell lines. RNase R treatment, gel-electrophoresis, and RNA fluorescent hybridization (FISH) were used to characterize the circRNAs. Subsequently, the Cell Counting Kit-8 assay (CCK8), transwell and wound healing assays were performed to assess circRNA function. Meanwhile, dual-luciferase reporter and western blot were used to clarify the associated molecular mechanisms. : Circ0036602 was upregulated in HPV-16 positive CC and correlated with a poor prognosis. Moreover, circ0036602 expression significantly correlated with the clinicopathologic characteristics. Knockdown of circ0036602 inhibited CC cell proliferation, migration, and invasion. Further studies showed that circ0036602 could bind to miR-34-5p and miR-431-5p to regulate the expression of the target gene HMGB1. : Taken together, our findings suggest that circ0036602 is a tumor-promoting circRNA that promotes CC cells by sponging miR-34-5p and miR-431-5p to regulate HMGB1. Circ0036602 has huge prospects as a potential therapeutic target for CC patients.
宫颈癌(CC)是全球最常见的女性恶性肿瘤之一。越来越多的证据表明,环状RNA(circRNA)参与包括CC在内的各种癌症的发病机制。然而,其表达谱和潜在分子机制仍 largely未知。
在本研究中,应用高通量测序来鉴定HPV-16阳性CC组织中的circRNA。进行定量实时PCR(qRT-PCR)以验证CC组织和细胞系中的表达。使用RNase R处理、凝胶电泳和RNA荧光杂交(FISH)来表征circRNA。随后,进行细胞计数试剂盒-8检测(CCK8)、transwell和伤口愈合检测以评估circRNA功能。同时,使用双荧光素酶报告基因和蛋白质印迹来阐明相关分子机制。
Circ0036602在HPV-16阳性CC中上调,且与预后不良相关。此外,circ0036602表达与临床病理特征显著相关。敲低circ0036602可抑制CC细胞增殖、迁移和侵袭。进一步研究表明,circ0036602可与miR-34-5p和miR-431-5p结合以调节靶基因HMGB1的表达。
综上所述,我们的研究结果表明,circ0036602是一种促肿瘤circRNA,通过海绵吸附miR-34-5p和miR-431-5p来调节HMGB1从而促进CC细胞生长。Circ0036602作为CC患者潜在的治疗靶点具有巨大前景。