Up-Regulation of LINC00665 Facilitates the Malignant Progression of Prostate Cancer by Epigenetically Silencing KLF2 Through EZH2 and LSD1

This study aimed to explore the role of LINC00665 on the proliferation and metastasis of PCa, and the potential regulatory mechanisms were also investigated. LINC00665 expression level in 50 pairs of PCa tissues and adjacent ones was studied by qRT-PCR, and the associations between LINC00665 and clinicopathological characteristics of PCa patients were analyzed. Control group (sh-NC) and LINC00665 knockdown group (sh-LINC00665) were set in 22RV1 and DU145 cells, respectively. The biological function of LINC00665 in PCa cell lines were assessed by CCK-8, EdU, Transwell assays and nude mouse xenograft model. In addition, Luciferase reporter, RIP, and ChIP assays were also used to determine the regulation mechanism of LINC00665 in PCa. In this study, our data showed that LINC00665 expression level in PCa cancer tissues was significantly upregulated, compared with that in adjacent ones. Besides, the similar results were found in PCa cell lines. Knockdown of LINC00665 significantly attenuated the proliferation and migration ability of PCa cell lines, compared to sh-NC. Mechanically, LINC00665 could interact with EZH2 and LSD1, recruiting them to KLF2 promoter region to inhibit its transcription. Moreover, the tumor-suppressive effects mediated by LINC00665 knockdown were greatly reversed following down-regulation of KLF2. Also, the suppression of LINC00665 impaired tumor growth of PCa in vivo. In summary, LINC00665 exerts oncogenic functions in PCa by epigenetically silencing KLF2 expression through binding to EZH2 and LSD1, illuminating a novel mechanism of LINC00665 in the malignant progression of PCa and furnishing a prospective therapeutic biomarker to combat PCa.