Background Circular RNA Itchy E3 ubiquitin protein ligase (Circ-ITCH) is significantly down-regulated in various kinds of tumors, however, the mechanisms of action and functions of circITCH gene in prostate cancer (PC) are still under investigation. The mail goal of this research was to study the functional role of Circ-ITCH gene in prostate cancer and to illuminate the function role of circ-ITCH gene in prostate cancer by targeting miR-17-5p/HOXB13. Methods RT-qPCR was applied to measure the expression level of circ-ITCH and miR-17-5p in PC cell lines and tissues. CCK-8, colony formation, Brdu incorporation labeling and flow cytometry assays were applied to detect the effects of circ-ITCH and miR-17-5p on proliferation and cell apoptosis. Target gene prediction and screening, luciferase reporter gene assays were utilized to assess downstream target genes of miR-17-5p and Circ-ITCH. The protein and expression of HOXB13 gene were measured by Western blotting and RT-qPCR. Results CircITCH was significantly reduced in PC cell lines and tissues. Low circITCH expression level was highly related with preoperative PSA, tumor stage and Gleason score. Overexpression of circITCH can inhibit the malignant phenotype of prostate cancer. There was a high negative relationship between the expression level of microRNA-17-5p and circITCH in PC tissues, however, there existed a positive relationship between the expression of HOXB13 and circITCH. CircITCH acted as a sponge of miR-17-5p to increase HOXB13 gene expression. In addition, miR-17-5p overexpression or HOXB13 silencing can reduce the carcinogenic effects of circICCH in prostate cancer. Conclusion CircITCH promoted prostate cancer progression by regulating the HOXB13/miR-17-5p axis, and circITCH have a potential usage as therapeutic target for PC tumors.

中文翻译：

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环状 RNA ITCH 通过海绵状 miR-17-5p 增加 HOXB13 表达来抑制前列腺癌进展。


背景 环状RNA Itchy E3泛素蛋白连接酶（Circ-ITCH）在多种肿瘤中显着下调，然而，circITCH基因在前列腺癌（PC）中的作用机制和功能仍在研究中。本研究的主要目的是研究Circ-ITCH基因在前列腺癌中的功能作用，并通过靶向miR-17-5p/HOXB13来阐明circ-ITCH基因在前列腺癌中的功能作用。方法采用RT-qPCR检测PC细胞系和组织中circ-ITCH和miR-17-5p的表达水平。应用CCK-8、集落形成、Brdu掺入标记和流式细胞术检测circ-ITCH和miR-17-5p对增殖和细胞凋亡的影响。利用靶基因预测和筛选、荧光素酶报告基因测定来评估miR-17-5p和Circ-ITCH的下游靶基因。通过Western blotting和RT-qPCR检测HOXB13基因的蛋白和表达。结果 PC 细胞系和组织中的 CircITCH 显着减少。 circITCH低表达水平与术前PSA、肿瘤分期和Gleason评分高度相关。 circITCH的过度表达可以抑制前列腺癌的恶性表型。 PC组织中microRNA-17-5p的表达量与circITCH呈高度负相关，而HOXB13的表达量与circITCH呈正相关。 CircITCH 作为 miR-17-5p 的海绵来增加 HOXB13 基因的表达。此外，miR-17-5p过表达或HOXB13沉默可以降低circICCH在前列腺癌中的致癌作用。 结论 CircITCH通过调控HOXB13/miR-17-5p轴促进前列腺癌进展，具有作为PC肿瘤治疗靶点的潜在用途。