Abstract
BackgroundCircular 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.MethodsRT-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.ResultsCircITCH 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.ConclusionCircITCH promoted prostate cancer progression by regulating the HOXB13/miR-17-5p axis, and circITCH have a potential usage as therapeutic target for PC tumors.
Highlights
Circular RNA Itchy E3 ubiquitin protein ligase (Circ-ITCH) is significantly down-regulated in various kinds of tumors, the mechanisms of action and functions of circITCH gene in prostate cancer (PC) are still under investigation
For the past few years, the occurrence rate of prostate cancer in males has increased year by year, which is closely related to the continuous growth of life expectancy, the aging of the population, the change of
CircITCH expression levels were significantly reduced in PC cell lines with a comparison to human prostate epithelial cell line RWPE-1 (Fig. 1b)
Summary
Circular RNA Itchy E3 ubiquitin protein ligase (Circ-ITCH) is significantly down-regulated in various kinds of tumors, the mechanisms of action and functions of circITCH gene in prostate cancer (PC) are still under investigation. PC (short for prostate cancer) is a popular malignant tumor in men [1, 2]. For the past few years, the occurrence rate of prostate cancer in males has increased year by year, which is closely related to the continuous growth of life expectancy, the aging of the population, the change of. Research on the pathogenesis of prostate cancer has never stopped, from proteomics to genomics, from DNA to RNA, from encoding RNA to non-coding RNA [10, 11]. Researchers have put a lot of effort into the study of prostate cancer, the mechanism of action for the pathogenesis of prostate cancer has not been unveiled. With the advancement of science and technology, non-coding RNAs that cannot encode proteins after transcription gradually enter the field of view
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