HECTD2/TNFAIP1 Axis Regulating the p38/JNK Pathway to Promote an Inflammatory Response in Renal Cell Carcinoma Cells.

BACKGROUND/AIM: The underlying processes of renal cell carcinoma (RCC), one of the deadliest malignancies of the urinary system, are still poorly understood. HECT domain E3 ubiquitin protein ligase 2 (HECTD2) is an E3 ubiquitin ligase implicated in the pulmonary inflammatory response. This study investigated the impact of HECTD2 on regulating inflammation in RCC cells and its potential mechanisms. MATERIALS AND METHODS: HECTD2 expression in RCC tissues was examined. Immunoprecipitation and western blot (WB) analysis confirmed that HECTD2 up-regulated euchromatic histone lysine methyltransferase 2 (EHMT2) protein degradation. ChIP experiments validated tumor necrosis factor α Inducing protein 1 (TNFAIP1) as a direct target of EHMT2. qRT-PCR determined HECTD2 and TNFAIP1 expression in RCC cells. Cell viability was assayed via CCK-8. ELISA was employed to measure the expression of IL-6, TNF-α, IL-8, and IL-1ß. WB analysis was conducted to test p38/JNK pathway-related protein (p38, p-p38, JNK, and p-JNK) expression. RESULTS: HECTD2 and TNFAIP1 were significantly up-regulated in RCC patient tissues and cells. Subsequent investigations revealed that HECTD2 promoted an inflammatory response in RCC cells. Additionally, HECTD2 up-regulated TNFAIP1 expression, and high TNFAIP1 expression could reverse the repressive impact of low HECTD2 expression on the inflammatory response in RCC cells. Rescue experiments demonstrated that the addition of p38/JNK pathway inhibitors attenuated the impact of TNFAIP1 overexpression on the RCC inflammatory response. CONCLUSION: Our findings establish a new mechanism by which HECTD2 exerts a pro-inflammatory role in RCC cells and present a prospective method for an anti-inflammatory intervention targeting the HECTD2/TNFAIP1 axis in malignancies.

Brevilin A shows an anti-tumor role in prostate cancer via the lncRNA H19/miR-194/E2F3 signaling pathway.

Brevilin A, a natural sesquiterpene lactone extracted from Centipeda minima, has been found with antitumor properties. Our study probed the functions of Brevilin A in prostate cancer cells and the mechanisms among Brevilin A, lncRNA H19, miR-194, and E2F3 on the biological behaviors of the cells. CCK8, Transwell, and TUNEL staining assays examined the impact of Brevilin A on prostate cancer cell proliferation, migration, invasion, and apoptosis, respectively. qRT-PCR and western blot determined lncRNA H19, miR-194, and E2F3 profiles. The influence of Brevilin A on the profiles of lncRNA H19, miR-194, and E2F3 was measured. A xenograft model of prostate cancer nude mice was taken to confirm the impact of Brevilin A and lncRNA H19 on cancer cell growth. Consequently, Brevilin A dampened prostate cancer cell proliferation, migration, and invasion, suppressed the expressions of lncRNA H19 and E2F3, and enhanced miR-194 level. LncRNA H19 and E2F3 were uplifted, whereas miR-194 was abated in prostate cancer cells and tissues. LncRNA H19 targeted miR-194 to positively modulate E2F3 expression, boosted DU145 cell proliferation, invasion, and migration, and curbed apoptosis. In the xenograft model, Brevilin A repressed tumor growth, whereas lncRNA H19 fostered tumor growth. Brevilin A suppressed the promotive effect of lncRNA H19 in PC cell growth in vivo. To conclude, Brevilin A modulates the biological behaviors of prostate cancer cells via the lncRNA H19/miR-194/E2F3 axis. Brevilin A exerts an anti-tumor function in prostate cancer.

Development and Verification of Prognostic Nomogram for Penile Cancer Based on the SEER Database.

Aim: We aimed to establish a prognostic nomogram for penile cancer (PC) patients based on the Surveillance, Epidemiology, and End Results Program (SEER) database. Methods: Data from 1643 patients between 2010 and 2015 were downloaded and extracted from the SEER database. They were randomly divided into the development group (70%) and the verification group (30%), and then, univariate and multivariate Cox proportional hazards regression, respectively, was used to explore the possible risk factors of PC. The factors significantly related to overall survival (OS) and cancer-specific survival (CSS) were used to establish the nomogram, which was assessed via the concordance index (C-index), receiver operating characteristic (ROC) curve, and calibration curve. An internal validation was conducted to test the accuracy and effectiveness of the nomogram. Kaplan-Meier calculation was used to predict the further OS and CSS status of these patients. Results: On multivariate Cox proportional hazards regression, the independent prognostic risk factors associated with OS were age, race, marital status, N/M stage, surgery, surgery of lymph nodes, and histologic type, with a moderate C-index of 0.737 (95% confidence interval (CI): 0.713-0.760) and 0.766 (95% CI: 0.731-0.801) in the development and verification groups, respectively. The areas under the ROC (AUC) of 3- and 5-year OS were 0.749 and 0.770, respectively. While marital status, N/M stage, surgery, surgery of lymph nodes, and histologic type were significantly linked to PC patients' CSS, which have better C-index of 0.802 (95% confidence interval (CI): 0.771-0.833) and 0.82 (95% CI: 0.775-0.865) in the development and verification groups, and the AUC of 3- and 5-year CSS were 0.766 and 0.787. Both of the survival calibration curves of 3- and 5-year OS and CSS brought out a high consistency. Conclusion: Our study produced a satisfactory nomogram revealing the survival of PC patients, which could be helpful for clinicians to assess the situation of PC patients and to implement further treatment.

Developing standards to support the clinical translation of stem cells.

Stem cells, which could be developed as starting or raw materials for cell therapy, hold tremendous promise for regenerative medicine. However, despite multiple fundamental and clinical studies, clinical translation of stem cells remains in the early stages. In contrast to traditional chemical drugs, cellular products are complex, and efficacy can be altered by culture conditions, suboptimal cell culture techniques, and prolonged passage such that translation of stem cells from bench to bedside involves not only scientific exploration but also normative issues. Establishing an integrated system of standards to support stem cell applications has great significance in efficient clinical translation. In recent years, regulators and the scientific community have recognized gaps in standardization and have begun to develop standards to support stem cell research and clinical translation. Here, we discuss the development of these standards, which support the translation of stem cell products into clinical therapy, and explore ongoing work to define current stem cell guidelines and standards. We also introduce general aspects of stem cell therapy and current international consensus on human pluripotent stem cells, discuss standardization of clinical-grade stem cells, and propose a framework for establishing stem cell standards. Finally, we review ongoing development of international and Chinese standards supporting stem cell therapy.