The Role of Linc00467/TRAF5 in Promoting the Malignant Progression of Prostate Cancer and its Mechanism

Abstract

Abstract Background Prostate cancer (PCa) is a commonly occurring cancer in the prostate. However, its pathogenesis is complex and remains largely unknown. This study aims to uncover the biological role of Linc00467/TRAF5 in influencing the progression of PCa and to provide novel directions for clinical treatment of PCa. Methods Linc00467 and TRAF5 were screened from PIA through chip detection in our previous study. Linc00467 and TRAF5 expression was verified using RT-qPCR in PC3, DU145, and normal human prostate epithelial cell line (HPrEC). Clinical specimens were collected to measure the expression of Linc00467 and TRAF5 in normal prostate tissue, PIA tissue, and PCa tissue using RT-qPCR. To further elucidate the regulatory effects of Linc00467 on TRAF5, siLinc00467 (SH4) was transfected into PCa cell lines (PC3 and DU145), and the expression of TRAF5 was detected by Western-blot. To study the impact of Linc00467 and TRAF5 on the biological behavior of PCa cells, we transfected siLinc00467 (SH4), overexpressed TRAF5 plasmid (Ov-TRAF5), and overexpressed siLinc00467 + TRAF5 plasmid into PC3 and DU145 cells, respectively. Next, we performed specific assays (MTT assay, scarification test, Transwell, Tunel, and flow cytometry) to analyze the effects of Linc00467 and TRAF5 on proliferation, migration, invasion, and apoptosis of PCa cells (PC3 and DU145). We also utilized a tumor-bearing nude mice model to understand the effects of Linc00467 and TRAF5 on tumor growth. Results The experimental results demonstrate that Linc00467 is highly expressed in PCa cell lines (PC3 and DU145), while the expression of TRAF5 is low. We found a similar pattern in clinical specimens (PIA and PCa tissues) where in Linc00467 was highly expressed and TRAF5 was downregulated. Inhibiting Linc00467 can promote TRAF5 expression, significantly reducing the proliferation, migration, and invasion of PCa cells (PC3 and DU145) and promoting apoptosis. The experiment on tumor-bearing nude mice showed that Linc00467 inhibition and overexpressed TRAF5 could inhibit tumor growth. Conclusion Our study suggests that Linc00467 is a tumor-promoting gene in PCa, while TRAF5 is a tumor suppressor gene. Furthermore, Linc00467 has a regulatory effect on TRAF5. The tumor-promoting effect of Linc00467 may be exerted by regulating TRAF5, but its specific mechanism needs to be explored further.