Prostate cancer (PCa) is a highly malignant tumor, with increasing incidence and mortality rates worldwide. The aim of this study was to identify the prognostic lncRNAs and construct an lncRNA signature for PCa diagnosis by the interaction network between lncRNAs and protein-coding genes (PCGs). The differentially expressed lncRNAs (DElncRNAs) and PCGs (DEPCGs) between PCa and normal prostate tissues were screened from The Cancer Genome Atlas (TCGA) database. The DEPCGs were functionally annotated in terms of the enriched pathways. Weighted gene co-expression network analysis (WGCNA) of 104 PCa samples identified 15 co-expression modules, of which the Turquoise module was negatively correlated with cancer and included 5 key lncRNAs and 47 PCGs. KEGG pathway analyses of the core 47 PCGs showed significant enrichment in classic PCa-related pathways, and overlapped with the enriched pathways of the DEPCGs. LINC00857, LINC00900, LINC00908, LINC00900, SNHG3 and FENDRR were significantly associated with the survival of PCa and have not been reported previously. Finally, Multivariable Cox regression analysis was used to establish a prognostic risk formula, and the patients were accordingly stratified into the low- and high-risk groups. The latter had significantly worse OS compared to the low-risk group (P < 0.01), and the area under the receiver operating characteristic curve (ROC) of 14-year OS was 0.829. The accuracy of our prediction model was determined by calculating the corresponding concordance index (C-index) and risk curves. In conclusion, we established a 5-lncRNA prognostic signature that provides insights into the biological and clinical relevance of lncRNAs in PCa.

Histone deacetylases 1 (HDAC1), an enzyme that functions to remove acetyl molecules from ε-NH3 groups of lysine in histones, eliminates the histone acetylation at the promoter regions of tumor suppressor genes to block their expression during tumorigenesis. However, it remains unclear why HDAC1 fails to impair oncogene expression. Here we report that HDAC1 is unable to occupy at the promoters of oncogenes but maintains its occupancy with the tumor suppressors due to its interaction with CREPT (cell cycle-related and expression-elevated protein in tumor, also named RPRD1B), an oncoprotein highly expressed in tumors. We observed that CREPT competed with HDAC1 for binding to oncogene (such as CCND1, CLDN1, VEGFA, PPARD and BMP4) promoters but not the tumor suppressor gene (such as p21 and p27) promoters by a chromatin immunoprecipitation (ChIP) qPCR experiment. Using immunoprecipitation experiments, we deciphered that CREPT specifically occupied at the oncogene promoter via TCF4, a transcription factor activated by Wnt signaling. In addition, we performed a real-time quantitative PCR (qRT-PCR) analysis on cells that stably over-expressed CREPT and/or HDAC1, and we propose that HDAC1 inhibits CREPT to activate oncogene expression under Wnt signaling activation. Our findings revealed that HDAC1 functions differentially on tumor suppressors and oncogenes due to its interaction with the oncoprotein CREPT.

Background: Immunodeficiency diseases (IDDs) are associated with an increased proportion of cancer-related morbidity. However, the relationship between IDDs and malignancy readmissions has not been well described. Understanding this relationship could help us to develop a more reasonable discharge plan in the special tumor population. Methods: Using the Nationwide Readmissions Database, we established a retrospective cohort study that included patients with the 16 most common malignancies, and we defined two groups: non-immunodeficiency diseases (NOIDDs) and IDDs. Results: To identify whether the presence or absence of IDDs was associated with readmission, we identified 603,831 patients with malignancies at their time of readmission in which 0.8% had IDDs and in which readmission occurred in 47.3%. Compared with NOIDDs, patients with IDDs had a higher risk of 30-day (hazard ratio (HR) of 1.32; 95% CI of 1.25–1.40), 90-day (HR of 1.27; 95% CI of 1.21–1.34) and 180-day readmission (HR of 1.28; 95% CI of 1.22–1.35). More than one third (37.9%) of patients with IDDs had readmissions that occurred within 30 days and most (82.4%) of them were UPRs. An IDD was an independent risk factor for readmission in patients with colorectal cancer (HR of 1.32; 95% CI of 1.01–1.72), lung cancer (HR of 1.23; 95% CI of 1.02–1.48), non-Hodgkin’s lymphoma (NHL) (HR of 1.16; 95% CI of 1.04–1.28), prostate cancer (HR of 1.45; 95% CI of 1.07–1.96) or stomach cancer (HR of 2.34; 95% CI of 1.33–4.14). Anemia (44.2%), bacterial infections (28.6%) and pneumonia (13.9%) were the 30-day UPR causes in these populations. (4) Conclusions: IDDs were independently associated with higher readmission risks for some malignant tumors. Strategies should be considered to prevent the causes of readmission as a post discharge plan.

Background/Objectives: Tumors are induced by overactivation of oncogenes and loss of tumor suppressor genes. Recently, a family of proteins containing CID (C-terminal domain (CTD)-interacting domain) domains, named CREPT/RPRD1B and p15RS/RPRD1A, has been identified to be involved in tumorigenesis through the regulation of the cell cycle. Interestingly, while p15RS was shown to inhibit cell proliferation, CREPT was demonstrated to promote tumorigenesis by accelerating tumor cell cycle progression. Methods: To decipher why these two proteins function oppositely, we aimed to reveal the disparities in their clinical outcomes and protein properties. Results: We observed that CREPT and p15RS are both highly expressed in tumors, but with opposite prognostic implications. We confirmed that CREPT promotes, but p15RS inhibits cell proliferation via regulation of Wnt/β-catenin signaling activation. The CID domain of CREPT differs from that of p15RS in conformation and charge distribution. CREPT exhibits a significantly stronger oligomerization capacity than p15RS, which is mediated by the CCT (coiled-coil terminus) domain. We demonstrated that the differences in both CID and CCT domains between CREPT and p15RS contribute to their opposite physiological functions. Conclusions: In conclusion, our results demonstrate that despite high primary sequence similarity, CREPT and p15RS exhibit distinctive biochemical properties. These differences ultimately explain their functional divergence in tumorigenesis and offer novel insights into CREPT-targeted drug design.