CircPDSS1 accelerates malignant progression of renal cell carcinoma through sponging of miR-182-5p

IF 0.6 4区 医学 Q4 PHARMACOLOGY & PHARMACY
Jia Wang, Yan Li, Yangsong Ou, Wan Qin, Wukui Huang, Cengceng Lu, Rongyan Ma, Rui Han, Hu Han
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Abstract

Purpose: To investigate the biological function and mechanisms of circPDSS1 in triggering malignant progression of renal cell carcinoma (RCC). Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to determine circPDSS1 levels in 50 pairs of RCC and para-cancerous tissues. The relationship between circPDSS1 level and pathological indices in RCC patients was analyzed, while the in vitro effect of circPDSS1 in regulating RCC proliferation was assessed using cell counting kit-8 (CCK-8), colony formation and 5- ethynyl-2’- deoxyuridine (EdU) assay. The sponge effect of circPDSS1 on miR-182-5p was examined by bioinformatics analysis and dual- luciferase reporter assay, while their involvement in mediating malignant progression of RCC was analyzed using rescue experiments. In vivo, the influence of circPDSS1 on RCC growth was determined by establishing a xenograft model in nude mice. Thereafter, RCC tissues were harvested from mice to assess relative levels of miR-182-5p and Ki-67. Results: CircPDSS1 was highly expressed in RCC tissues (p < 0.05). A high level of circPDSS1 correlated with advanced tumor staging and low overall survival. Knockdown of circPDSS1 inhibited RCC cell proliferation, and CircPDSS1 sponged and negatively regulated miR-182-5p (p < 0.05). MiR182-5p was able to abolish regulatory effect of circPDSS1 on malignant proliferative potential in RCC cells. In nude mice bearing RCC, in vivo knockdown of circPDSS1 slowed down tumor growth and decreased positive expression of Ki-67 in tumor tissues (p < 0.05). Conclusion: CircPDSS1 predicts tumor stage and prognosis in RCC patients. It triggers malignant progression of RCC through sponging of miR-182-5p.
CircPDSS1通过海绵化miR-182-5p加速肾细胞癌的恶性进展
目的:探讨circPDSS1在肾细胞癌(RCC)恶性进展中的生物学功能及机制。方法:采用实时定量聚合酶链反应(qRT-PCR)检测50对RCC及癌旁组织中circPDSS1水平。分析circPDSS1水平与RCC患者病理指标的关系,并通过细胞计数试剂盒-8 (CCK-8)、集落形成和5-乙基-2′-脱氧尿苷(EdU)法评估circPDSS1在体外调节RCC增殖的作用。通过生物信息学分析和双荧光素酶报告基因检测检测circPDSS1对miR-182-5p的海绵效应,并通过挽救实验分析其介导RCC恶性进展的作用。在体内,通过建立裸鼠异种移植模型来确定circPDSS1对RCC生长的影响。此后,收集小鼠的RCC组织以评估miR-182-5p和Ki-67的相对水平。结果:CircPDSS1在RCC组织中高表达(p <0.05)。高水平的circPDSS1与晚期肿瘤分期和低总生存率相关。敲低circPDSS1可抑制RCC细胞增殖,circPDSS1可抑制miR-182-5p (p <0.05)。MiR182-5p能够消除circPDSS1对RCC细胞恶性增殖潜能的调节作用。在膀胱癌裸鼠中,体内敲低circPDSS1可减缓肿瘤生长,降低肿瘤组织中Ki-67的阳性表达(p <0.05)强生# x0D;结论:CircPDSS1可预测RCC患者的肿瘤分期和预后。它通过海绵miR-182-5p触发RCC的恶性进展。
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来源期刊
CiteScore
1.00
自引率
33.30%
发文量
490
审稿时长
4-8 weeks
期刊介绍: We seek to encourage pharmaceutical and allied research of tropical and international relevance and to foster multidisciplinary research and collaboration among scientists, the pharmaceutical industry and the healthcare professionals. We publish articles in pharmaceutical sciences and related disciplines (including biotechnology, cell and molecular biology, drug utilization including adverse drug events, medical and other life sciences, and related engineering fields). Although primarily devoted to original research papers, we welcome reviews on current topics of special interest and relevance.
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