Kidney cancer ranks as one of the top 10 causes of cancer death; this cancer is difficult to detect, difficult to treat, and poorly understood. The most common subtype of kidney cancer is clear cell renal cell carcinoma (ccRCC) and its progression is influenced by complex gene interactions. Few clinical studies have investigated the molecular markers associated with the progression of ccRCC. In this study, we collected microarray profiles of 72 ccRCCs and matched normal samples to identify differentially expressed genes (DEGs). Then a weighted gene co-expression network analysis (WGCNA) was conducted to identify co-expressed gene modules. By relating all co-expressed modules to clinical features, we found that the brown module and Fuhrman grade had the highest correlation (r = −0.8, p = 1e-09). Thus, the brown module was regarded as a clinically significant module and subsequently analyzed. Functional annotation showed that the brown module focused on metabolism-related biological processes and pathways, such as fatty acid oxidation and amino acid metabolism. We then performed a protein-protein interaction (PPI) network to identify the hub nodes in the brown module. It is worth noting that only one candidate, acetyl-CoA acetyltransferase (ACAT1), was considered to be the final target most relevant to the Fuhrman grade of ccRCC, by applying the intersection of hub genes in the co-expressed network and the PPI network. ACAT1 was subsequently validated using another two external microarray datasets and the TCGA dataset. Intriguingly, validation results indicated that ACAT1 was negatively correlated with four grades of ccRCC, which was also consistent with our results from qRT-PCR analysis and immunohistochemistry staining of clinical samples. Overexpression of ACAT1 inhibited the proliferation and migration of human ccRCC cells in vitro. In addition, the Kaplan-Meier survival curve showed that patients with a lower expression of ACAT1 showed a significantly lower overall survival rate and disease-free survival rate, indicating that ACAT1 could act as a prognostic and recurrence/progression biomarker of ccRCC. In summary, we found and confirmed that ACAT1 might help to identify the progression of ccRCC, which might have important clinical implications for enhancing risk stratification, therapeutic decision, and prognosis prediction in ccRCC patients.

E3 ubiquitin ligase RNF126 (ring finger protein 126) is highly expressed in various cancers and strongly associated with tumorigenesis. However, its specific function in bladder cancer (BCa) is still debatable. Here, we found that RNF126 was significantly upregulated in BCa tissue by TCGA database, and our studies indicated that downregulation of RNF126 significantly inhibited cell proliferation and metastasis through the EGFR/PI3K/AKT signaling pathway in BCa cells. Furthermore, we identified PTEN, an inhibitor of the PI3K/AKT signaling pathway, as a novel substrate for RNF126. By co-immunoprecipitation assays, we proved that RNF126 directly interacts with PTEN. Predominantly, PTEN binds to the C-terminal containing the RING domain of RNF126. The in vivo ubiquitination assay showed that RNF126 specifically regulates PTEN stability through poly-ubiquitination. Furthermore, PTEN knockdown restored cell proliferation, metastasis, and tumor formation of BCa cells inhibited by RNF126 silencing in vitro and in vivo. In conclusion, these results identified RNF126 as an oncogene that functions through ubiquitination and degradation of PTEN in BCa.

Abnormal methylation of secreted frizzled-related proteins (SFRPs) has been observed in various human cancer types. The loss of SFRP gene expression induces the activation of the Wnt pathway and is a vital mechanism for tumorigenesis and development. The aim of the present systematic review was to assess the association between SFRP methylation and cancer risk. A meta-analysis was systematically conducted to assess the clinicopathological significance of SFRP methylation in cancer risk. The Cochrane Library, PubMed and Web of Science databases were comprehensively searched, and 83 publications with a total of 21,612 samples were selected for the meta-analysis. The pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated to evaluate the degree of associations between SFRP promoter methylation and cancer risk. Subgroup analysis, meta regression and sensitivity analysis were used to identify the potential sources of heterogeneity. SFRP1, SFRP2, SFRP4 and SFRP5 hypermethylation was significantly associated with cancer risk, with ORs of 8.48 (95% CI, 6.26–11.49), 8.21 (95% CI, 6.20–10.88), 11.41 (95% CI, 6.42–20.30) and 6.34 (95% CI, 3.86–10.42), respectively. SFRP2 methylation was significantly associated with differentiation in colorectal cancer (OR, 2.16; 95% CI, 1.02–4.56). The results of the present study demonstrated that SFRP methylation may contribute to carcinogenesis, especially in certain cancer types, including hepatocellular carcinoma and colorectal cancer.

Stem cell memory T (TSCM) and central memory T (TCM) cells can rapidly differentiate into effector memory (TEM) and terminal effector (TEF) T cells, and have the most potential for immunotherapy. In this study, we found that the frequency of TSCM and TCM cells in the CD8+ population dramatically decreased together with increases in TEM and TEF cells, particularly in younger patients with acute myeloid leukemia (AML) (< 60 years). These alterations persisted in patients who achieved complete remission after chemotherapy. The decrease in TSCM and TCM together with the increase in differentiated TEM and TEF subsets in CD8+ T cells may explain the reduced T cell response and subdued anti-leukemia capacity in AML patients.

Prostate cancer (PCa) is one of the most commonly diagnosed human cancers in males. Nearly 191,930 new cases and 33,330 new deaths of PCa are estimated in 2020. Androgen and androgen receptor pathways played essential roles in the pathogenesis of PCa. Androgen depletion therapy is the most used therapies for primary PCa patients. However, due to the high relapse and mortality of PCa, developing novel noninvasive therapies have become the focus of research. Melatonin is an indole-like neurohormone mainly produced in the human pineal gland with a prominent anti-oxidant property. The anti-tumor ability of melatonin has been substantially confirmed and several related articles have also reported the inhibitory effect of melatonin on PCa, while reviews of this inhibitory effect of melatonin on PCa in recent 10 years are absent. Therefore, we systematically discuss the relationship between melatonin disruption and the risk of PCa, the mechanism of how melatonin inhibited PCa, and the synergistic benefits of melatonin and other drugs to summarize current understandings about the function of melatonin in suppressing human prostate cancer. We also raise several unsolved issues that need to be resolved to translate currently non-clinical trials of melatonin for clinic use. We hope this literature review could provide a solid theoretical basis for the future utilization of melatonin in preventing, diagnosing and treating human prostate cancer.