Identification and verification of an ALYREF-involved 5-methylcytosine based signature for stratification of prostate cancer patients and prediction of clinical outcome and response to therapies.

OBJECTIVES: Due to the heterogeneity of PCa, the clinical indicators used for PCa can't satisfy risk prognostication and personalized treatment. It is imperative to develop novel biomarkers for prognosis prediction and therapy response in PCa. Accumulating evidence shows that non-mutational epigenetic reprogramming, independent from genomic instability and mutation, serves as a newly added hallmark in cancer progression. METHODS: In this study, we integrated multi-center cohorts (N > 1300) to develop a RNA 5-methylcytosine regulator-based signature, the m5C score. We performed unsupervised clustering and LASSO regression to identify novel m5C-related subtypes and calculate the m5C score. Then we assessed the role of m5C cluster and m5C score in several clinical aspects such as prognosis in various molecular subtypes, responses to chemotherapy, androgen receptor signaling inhibitor (ARSI) therapy and immunotherapy in PCa. Finally, we validated the cancer-promoting performance of ALYREF through clinical data analysis and experiments in vivo and in vitro. RESULTS: The investigation revealed that the m5C score could accurately predict the biochemical recurrence (BCR) in different subtypes (the PAM50 subtypes and immunophenotypes) and the responses to chemotherapy, ARSI therapy, and immunotherapy (PD1/PD-L1). A high m5C score indicated a poor BCR prognosis in every subtype of PCa, unfavorable responses in ARSI therapy and immunotherapy (PD1/PD-L1). Moreover, the m5C reader gene termed ALYREF, yielding the highest weighed coefficient, promoted PCa progression through in silico analysis and experimental validations (in vivo and in vitro). CONCLUSIONS: The m5C signature can function in many aspects of PCa, such as the development and prognosis of the disease, and multiple therapy responses. Further, the m5C reader, ALYREF, was identified as a prognostic biomarker and a potential therapeutic target for PCa. The m5C signature could act as a brand-new tool for predicting the prognosis of patients in different molecular subtypes and patients' therapy responses and promoting customized treatments.

Integrin-Linked Kinase (ILK) Regulates Urinary Stem Cells Differentiation into Smooth Muscle via NF-κB Signal Pathway.

OBJECTIVES: Urinary stem cells (USCs) have the capacity for unlimited growth and are promising tools for the investigations of cell differentiation and urinary regeneration. However, the limited life span significantly restricts their usefulness. This study is aimed at exploring the effect of integrin-linked kinase (ILK) on the smooth muscle cells (SMCs) differentiation of the dog USCs and investigating its molecular mechanism. METHODS: An immortalized USCs cell line with the molecular markers and biological functions was prepared. After successfully inducing the differentiation of USCs into SMCs, the expression level of the unique key factor and its mechanisms in this process was determined through real-time polymerase chain reaction, Western blot, or Immunofluorescence staining. RESULTS: We found that high cell density promoted USCs differentiation SMCs, and ILK was necessary for USCs differentiation into SMCs. Knocking down ILK decreased the expression of SMCs specific-marker, while using a selective ILK agonist increased the expression of SMCs specific-marker. Furthermore, ILK regulated SMCs differentiation in part through the activation of NF-κB pathway in USCs. A NF-κB activity assay showed overexpression of ILK could significantly upregulate NF-κB p50 expression, and NF-κB p50 acts as downstream signal molecular of ILK. CONCLUSION: High cell density induces the differentiation of USCs into SMCs, and ILK is a key regulator of myogenesis. Furthermore, NF-κB signaling pathway might play a crucial role in this process.

[Circumcision reduces the incidence of human papillomavirus infection in men].

OBJECTIVE: To investigate the association of circumcision with the incidence of human papillomavirus (HPV) infection in men. METHODS: We collected the samples from the surface of the coronal sulcus, glans penis, penile shaft and scrotum of 351 males examined for HPV infection in our hospital from January 2016 to August 2017, of whom 118 had received circumcision while the other 233 had not. We compared the incidence rate of HPV infection between the circumcision and non-circumcision groups and analyzed the association of the age of circumcision with the incidence of HPV infection. RESULTS: HPV infection was found in 135 (38.46%) of the males, 29 (24.58%) in the circumcision group and 106 (45.49%) in the non-circumcision group, significantly lower in the former than in the latter (χ² = 14.48, P < 0.01). The incidence rate of HPV infection was also remarkably lower in the males circumcised at ≤17 years (13.16% ï¼»5/38ï¼½) than in those circumcised at >17 years of age (30.0% ï¼»24/80ï¼½) (χ² = 3.942, P = 0.047). CONCLUSIONS: Male circumcision helps reduce the incidence rate of HPV infection in men and earlier surgery may achieve even better effect.