LncRNA LNC-565686 Promotes Proliferation of Prostate Cancer by Inhibiting Apoptosis through Stabilizing SND1.

Long non-coding RNAs (lncRNAs), typically more than 200 nt long, cannot encode proteins, but can regulate gene expression. They play an indispensable role in the occurrence and progression of various cancers. The main purpose of this study is to discuss the role and mechanism of LNC-565686 in prostate cancer. First, we found an increased expression of LNC-565686 in prostate cancer cells using RNA sequencing, which was further verified using qRT-PCR. Then, catRAPID was used to find that LNC-565686 might regulate SND1. Furthermore, a protein half-life experiment was performed to verify that LNC-565686 could stabilize the expression of SND1. In order to further explore the effects of LNC-565686 and SND1 on prostate cancer cells, we knocked down LNC-565686 and SND1 in prostate cancer cells, and verified using CCK8 and flow cytometry and western blot for the detection of apoptosis-related indicators. Collectively, we have found that LNC-565686 can promote the proliferation of prostate cancer cells and inhibit apoptosis by stabilizing the expression of SND1. Therefore, targeting LNC-565686 might be a new treatment for prostate cancer.

GOLM1 Promotes Epithelial-Mesenchymal Transition by Activating TGFß1/Smad2 Signaling in Prostate Cancer.

Background: Prostate cancer (PC) is one of the most commonly diagnosed cancer in men worldwide. Epithelial-mesenchymal transition (EMT) is considered to play a crucial role in the development of the metastatic castration-resistant prostate cancer, which causes the majority of the death cases in PC. Golgi membrane protein 1 (GOLM1) is highly expressed in PC and has been identified as a driver factor for EMT in various cancers. However, its biological functions and underlying mechanisms remain ambiguous in PC. Method: GOLM1 expression level of PC was detected by Western blot and immunohistochemistry analyses. To investigate GOLM1 functions in cancer cells, we overexpressed and knocked down GOLM1 in different prostate cancer cell lines. Transwell assay and wound healing assay were used to determine the role of GOLM1 in cell EMT, such as migration and invasion abilities. TGF-ß1/Smad2 signaling pathway downstream of GOLM1 was detected by Western blot and Transwell assay. Result: GOLM1 expression is up-regulated in PC and correlated with a worse prognosis. GOLM1 promotes the abilities of migration and invasion in PC cell lines (DU145 and LNCaP). Furthermore, TGF-ß1/Smad2 signaling is positively regulated by GOLM1 to facilitate EMT in PC, whereas this role can be restored by TGF-ß1 after GOLM1 knockdown or be abrogated by p-Smad inhibitor SB431542. Conclusion: GOLM1 is significantly upregulated in PC and acts as a critical oncogene by promoting PC cell EMT process by activating TGF-ß1/Smad2 signaling pathway. Therefore, GOLM1 has the potential to be a biomarker for PC diagnosis and to predict the prognosis of PC patients. It is of great significance to seek effective and specific inhibitor of GOLM1 for PC treatment as well.

LSD1 Promotes Prostate Cancer Cell Survival by Destabilizing FBXW7 at Post-Translational Level.

Prostate cancer (PCa) is the most common cancer in men and the fifth leading cause of cancer death worldwide. Unfortunately, castration-resistant prostate cancer (CRPCa) is incurable with surgical treat and prone to drug resistance. Therefore, it is of great importance to find a new target for treatment. LSD1 is up-regulated in PCa and related with prognosis. The high-expression LSD1 has been shown to be a potential target for treatment and is widely studied for its demethylase-activity. However, its demethylation-independent function remains to be elusive in PCa. Recent study shows that LSD1 can destabilize cancer suppressor protein FBXW7 without demethylation-function. Hence, we hope to investigate the impact of non-canonical function of LSD1 on PCa cell survival. We over-expressed FBXW7 gene through plasmid vector in LNCaP and PC3 cell lines and the result shows that up-regulated FBXW7 can suppress the viability of PC cell through suppressing oncoproteins, such as c-MYC, NOTCH-1. After FBXW7 function experiment on PC cell, we knock-down LSD1 gene in the same kinds of cell lines. In western blot assay, we detected that down-regulation of LSD1 will cause the increasing of FBXW7 protein level and decreasing of its targeting oncoproteins. And mRNA level of FBXW7 did not change significantly after LSD1 knock-down, which means LSD1 may destabilize FBXW7 by protein-protein interactions. Moreover, exogenous wild type LSD1 and catalytically deficient mutant K661A both can abrogate previous effect of LSD1 knock-down. Consequently, LSD1 may promote PC cell survival by destabilizing FBXW7 without its demethylase-activity. Next, we compared two kinds inhibitors, and found that SP-2509 (Allosteric inhibitor) treatment suppress the cancer cell survival by blocking the LSD1-FBXW7 interaction, which is an effect that GSK-2879552 (catalytic inhibitor) cannot achieve. This work revealed a pivotal function of LSD1 in PCa, and indicated a new direction of LSD1 inhibitor research for PCa treatment.