Abstract
Metastatic disease caused by castration-resistant prostate cancer (CRPC) is the principal cause of prostate cancer (PCa)-related mortality. CRPC occurs within 2–3 years of initiation of androgen deprivation therapy (ADT), which is an important factor of influencing PCa metastasis. Recent studies have revealed that non-coding RNAs in PCa can enhance metastasis and progression, while the mechanisms are still unclear. In this study, we reported that the long noncoding RNA-LINC00963 was increased in CRPC tissues and promoted migration of PCa cells in vitro and their metastasis in vivo. High levels of LINC00963 significantly decreased tumor suppressor miR-542-3p, whose levels in metastasis tissues were low compared to those in non-metastasis tissues. LINC00963 promotes and miR-542-3p inhibits metastasis. Furthermore, the expression levels of LINC00963 and miR-542-3p were positively and negatively associated with the expression of NOP2. We demonstrated that NOP2 promoted PCa by activating the epithelial-mesenchymal transition (EMT) pathway. For specific mechanism, dual luciferase reporter assays showed that miR-542-3p directly binds to both 3'-untranslated region (UTR) of LINC00963 and NOP2 mRNA. Taken together, our results show that LINC00963 acts as an inducer of PCa metastasis by binding miR-542-3p, thereby promoting NOP2. This axis may have diagnostic and therapeutic potential for advanced PCa.
Highlights
Prostate cancer (PCa) remains the second major cause of male cancer-associated death in the United States
To identify long noncoding RNAs (lncRNAs) that may be involved in the emergence of castration-resistant prostate cancer (CRPC), we first analyzed RNA sequencing (RNA-seq) data of 3 CRPC tissues and 3 normal prostate cancer (PCa) tissues from the Transgenic adenocarcinomas of mouse prostate (TRAMP) and ProbCre/Ptenfl/fl mouse models
We found that the expression levels of 159 and 185 lncRNAs in CRPC tissues from the TRAMP mouse (Figure 1C) and the ProbCre/Ptenfl/fl mouse (Figure 1D) were significantly changed (Fold change > 2, P < 0.05) compared to those of normal PCa tissues
Summary
Prostate cancer (PCa) remains the second major cause of male cancer-associated death in the United States. Androgen-deprivation therapy (ADT) is the primary treatment for patients with biochemically relapsed and metastatic PCa [1, 2]. Research has consistently shown that after an initial sensitivity to ADT, most patients generate resistance and progress to castration-resistant prostate cancer (CRPC) [3, 4]. Namely cabazitaxel, abiraterone, and enzalutamide, have prolonged the survival of patients with CRPC [5,6,7]. CRPC is an essential cause of distant metastasis of prostate cancer, but the mechanism is still unclear [8, 9]. Understanding the intrinsic mechanism of PCa metastasis is vitally crucial for future clinical management
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