Clear cell renal cell carcinoma (ccRCC) is the most common renal malignancy in adults, the incidence of which continues to increase. The lipid droplet protein perilipin 2 (PLIN2), which was originally considered an RNA transcript, is markedly expressed during adipocyte differentiation. In addition, it has been observed to be elevated in numerous types of cancer, including ccRCC; however, its essential function remains unclear in ccRCC. The present study examined the expression of PLIN2 in ccRCC, and aimed to determine the association between PLIN2 expression and patient survival. The present study mined the transcriptional, clinicopathological and survival data of PLIN2 in patients with ccRCC through The Cancer Genome Atlas. The expression levels of PLIN2 were also detected in human ccRCC tissues and cell lines by western blotting and immunohistochemistry, and its biological role was identified by functional analysis. The results demonstrated that PLIN2 was predominantly elevated in RCC tissues and cells. In addition, the expression levels of PLIN2 were significantly associated with various clinicopathological factors, and high PLIN2 expression was associated with a good prognosis. The results of a multivariate analysis demonstrated that high PLIN2 expression was an independent prognostic indicator of overall survival (hazard ratio, 0.586; P=0.001). Furthermore, PLIN2 knockdown promoted proliferation of ccRCC cells, and enhanced cell invasion and migration. These results suggested that PLIN2 may be considered a novel prognostic factor in ccRCC and a specific diagnostic indicator for patients with ccRCC. Furthermore, it could be a potential novel target for the clinical treatment of ccRCC.

Current endocrine therapy for prostate cancer (PCa) mainly inhibits androgen/androgen receptor (AR) signaling. However, due to increased intratumoural androgen synthesis and AR variation, PCa progresses to castration-resistant prostate cancer (CRPC), which ultimately becomes resistant to endocrine therapy. A search for new therapeutic perspectives is urgently needed. Methods: By screening lipid metabolism-related gene sets and bioinformatics analysis in prostate cancer database, we identified the key lipid metabolism-related genes in PCa. Bisulfite genomic Sequence Polymerase Chain Reaction (PCR) (BSP) and Methylation-Specific Polymerase Chain Reaction (PCR) (MSP) were preformed to detect the promoter methylation of ACSS3. Gene expression was analyzed by qRT-PCR, Western blotting, IHC and co-IP. The function of ACSS3 in PCa was measured by CCK-8, Transwell assays. LC/MS, Oil Red O assays and TG and cholesterol measurement assays were to detect the levels of TG and cholesterol in cells. Resistance to Enzalutamide in C4-2 ENZR cells was examined in a xenograft tumorigenesis model in vivo. Results: We found that acyl-CoA synthetase short chain family member 3 (ACSS3) was downregulated and predicted a poor prognosis in PCa. Loss of ACSS3 expression was due to gene promoter methylation. Restoration of ACSS3 expression in PCa cells significantly reduced LD deposits, thus promoting apoptosis by increasing endoplasmic reticulum (ER) stress, and decreasing de novo intratumoral androgen synthesis, inhibiting CRPC progression and reversing Enzalutamide resistance. Mechanistic investigations demonstrated that ACSS3 reduced LD deposits by regulating the stability of the LD coat protein perilipin 3 (PLIN3). Conclusions: Our study demonstrated that ACSS3 represses prostate cancer progression through downregulating lipid droplet-associated protein PLIN3.

Prostate cancer (PCa) is the second leading cause of death among American men.Increasing evidence has shown that long noncoding RNAs (lncRNAs) play important roles in tumorigenesis of PCa. In this study, we explored the biological functions of small nucleolar RNA host gene 12 (SNHG12) and investigated the interaction between miR-133b and SNHG12 in the progression of PCa. Data was downloaded from The Cancer Genome Atlas and Human Cancer Metastasis Database, and clinicopathological characteristics were analyzed with relapse-free survival rate. We detected SNHG12 expression level in PCa cells and tissues, and then analyzed its clinical significance, which revealed that SNHG12 has the potent to predict prognosis of PCa. Bioinformatic analysis revealed that SNHG12 was closely related to the progression of PCa and could target candidate microRNA (miR-133b). After transfecting SNHG12 silencing plasmid and miR-133b mimic/sponge, biological function assays were conducted and results illustrated that SNHG12 associated with miR-133b exerted biological effects on cancer cell growth, migration, and invasion. Direct interactions between miR-133b and SNHG12 have been found and SNHG12 acts as an oncogene to promote tumorigenesis of PCa by sponging tumor suppressor gene miR-133b. K E Y W O R D SSNHG12, miR-133b, prostate cancer, biomarker, tumorigenesis