LZTFL1 inhibits kidney tumor cell growth by destabilizing AKT through ZNRF1-mediated ubiquitin proteosome pathway.

LZTFL1 is a tumor suppressor located in chromosomal region 3p21.3 that is deleted frequently and early in various cancer types including the kidney cancer. However, its role in kidney tumorigenesis remains unknown. Here we hypothesized a tumor suppressive function of LZTFL1 in clear cell renal cell carcinoma (ccRCC) and its mechanism of action based on extensive bioinformatics analysis of patients' tumor data and validated it using both gain- and loss-functional studies in kidney tumor cell lines and patient-derive xenograft (PDX) model systems. Our studies indicated that LZTFL1 inhibits kidney tumor cell proliferation by destabilizing AKT through ZNRF1-mediated ubiquitin proteosome pathway and inducing cell cycle arrest at G1. Clinically, we found that LZTFL1 is frequently deleted in ccRCC. Downregulation of LZTFL1 is associated with a poor ccRCC outcome and may be used as prognostic maker. Furthermore, we show that overexpression of LZTFL1 in PDX via lentiviral delivery suppressed PDX growth, suggesting that re-expression of LZTFL1 may be a therapeutic strategy against ccRCC.

m6A-immune-related lncRNA prognostic signature for predicting immune landscape and prognosis of bladder cancer.

BACKGROUND: N6-methyladenosine (m6A) related long noncoding RNAs (lncRNAs) may have prognostic value in bladder cancer for their key role in tumorigenesis and innate immunity. METHODS: Bladder cancer transcriptome data and the corresponding clinical data were acquired from the Cancer Genome Atlas (TCGA) database. The m6A-immune-related lncRNAs were identified using univariate Cox regression analysis and Pearson correlation analysis. A risk model was established using least absolute shrinkage and selection operator (LASSO) Cox regression analyses, and analyzed using nomogram, time-dependent receiver operating characteristics (ROC) and Kaplan-Meier survival analysis. The differences in infiltration scores, clinical features, and sensitivity to Talazoparib of various immune cells between low- and high-risk groups were investigated. RESULTS: Totally 618 m6A-immune-related lncRNAs and 490 immune-related lncRNAs were identified from TCGA, and 47 lncRNAs of their intersection demonstrated prognostic values. A risk model with 11 lncRNAs was established by Lasso Cox regression, and can predict the prognosis of bladder cancer patients as demonstrated by time-dependent ROC and Kaplan-Meier analysis. Significant correlations were determined between risk score and tumor malignancy or immune cell infiltration. Meanwhile, significant differences were observed in tumor mutation burden and stemness-score between the low-risk group and high-risk group. Moreover, high-risk group patients were more responsive to Talazoparib. CONCLUSIONS: An m6A-immune-related lncRNA risk model was established in this study, which can be applied to predict prognosis, immune landscape and chemotherapeutic response in bladder cancer.

Gastroesophageal reflux is associated with an increased risk of gastric cardiac polyps: a case-control study of 140 cases.

BACKGROUND: The pathogenesis of gastric cardiac polyps is not yet clear, and there is little research on their clinical and histopathologic characteristics and correlation with gastroesophageal reflux. Early detection and treatment of premalignant lesions in this area can prevent the development of cancer. We aimed to evaluate the clinical and histopathologic characteristics and risk factors of gastric cardiac polyps to improve the current understanding of the disease. METHODS: Patients diagnosed with gastric cardiac polyps at the Third Affiliated Hospital of Sun Yat-Sen University between January 1, 2010, and December 31, 2019, were sought for the study. The exclusion criteria were missing clinical data, insufficient pathological reports, gastric malignancy, or a previous history of gastroduodenal surgery. Ultimately, 140 patients were included in the case group, while 140 patients diagnosed with chronic superficial gastritis from the same 10-year period were identified randomly and selected as a control group. The exclusion criteria for this group were the same as those for the case group. Patients in both groups were matched in age and gender to ensure comparability between the two groups. We evaluated and compared the demographic and clinical data and endoscopic impressions of each group and analyzed the endoscopic, histologic features of gastric cardiac polyps. RESULTS: Gastroesophageal reflux was significantly associated with a higher risk of gastric cardiac polyps after adjustment for other covariates [adjusted odds ratio (OR) =2.809; 95% confidence interval (CI): 1.178-6.697; P=0.020]. Most gastric polyps were single (97.9%), sessile (92.8%), and small polyps with a diameter less than 1 cm (88.6%). Most were located in the gastroesophageal junction region (65.0%) with a smooth surface (56.4%) or surface congestion (30.0%). Hyperplastic (inflammatory) polyps (88.0%) were the most common pathological type and comprised gastric-type foveolar epithelium, squamous epithelium, or admixture of the two epithelia, with a minority showing intestinal metaplasia, mild, or moderate epithelial dysplasia. CONCLUSIONS: Gastroesophageal reflux was associated with a significantly higher incidence of gastric cardiac polyps with a 2.8-fold increased risk. Most gastric cardiac polyps were found to be benign lesions and had a favorable prognosis in the clinic despite their malignant potential.

Overexpression of EIF5A2 in upper urinary tract urothelial carcinoma is a new independent prognostic marker of survival.

Aim: To study the expression of EIF5A2 in urinary tract urothelial carcinoma and its clinicopathological features and prognosis. Methods: EIF5A2 expression was detected via immunohistochemistry in 101 patients. Results: Kaplan-Meier analysis showed that the EIF5A2 low expression group had significantly longer overall survival (OS; p < 0.001) and progression-free survival (PFS; p < 0.001) than the EIF5A2 high expression group. The high expression of EIF5A2 significantly predict poor OS and PFS in the subset patients (p < 0.05). EIF5A2 was an independent prognostic factor for OS and PFS (p = 0.003 and p = 0.001). The established nomogram model and its calibration curve predicted the probability of survival accurately. Conclusion: EIF5A2 is a potential molecular marker of poor prognosis in urinary tract urothelial carcinoma.

RIN1 promotes renal cell carcinoma malignancy by activating EGFR signaling through Rab25.

We previously identified the important role of RIN1 expression in the prognosis of clear cell renal cell carcinoma (ccRCC). The role of RIN1 in ccRCC malignancy and underlying molecular mechanisms remain unclear. Here we report that ccRCC cells and tissues expressed more RIN1 than normal controls. Gain-of-function and loss-of-function studies demonstrated that RIN1 enhanced ccRCC cell growth, migration and invasion abilities in vitro and promoted tumor growth and metastasis in vivo. Mechanistic studies revealed that RIN1 has an activating effect on EGFR signaling in ccRCC. In addition, we unveil Rab25, a critical GTPase in ccRCC malignancy, as a functional RIN1 interacting partner. Knockdown of Rab25 eliminated the augmentation of carcinoma cell proliferation, migration and invasion by ectopic RIN1. We also confirmed that RIN1 and Rab25 expression correlates with the overall-survival of ccRCC patients from TCGA. These findings suggest that RIN1 plays an important oncogenic role in ccRCC malignancy by activation of EGFR signaling through interacting with Rab25, and RIN1 could be employed as an effective therapeutic target for ccRCC.

miR-106b-5p promotes renal cell carcinoma aggressiveness and stem-cell-like phenotype by activating Wnt/ß-catenin signalling.

PURPOSE: To examine the role of miR-106b-5p in regulating the cancer stem-cell-like phenotype in clear cell renal cell carcinomas (ccRCC). EXPERIMENTAL DESIGN: Real-time PCR was performed to evaluate miR-106b-5p levels in ccRCC cell lines and patients specimens. A series of in vivo and in vitro assays were performed to confirm the effect of miR-106b-5p on ccRCC stemness phenotype. RESULTS: ccRCC cells and tissues expressed more miR-106b-5p than normal controls. Gain- and loss-of-function studies demonstrated that overexpression of miR-106b-5p in ccRCC cells increased the spheres formation ability and the proportion of side population cells. Ectopic expression of miR-106b-5p in ccRCC cells increased tumour growth rates and the number of metastatic colonies in the lungs by using an orthotopic kidney cancer model and a tail vein injection model, respectively. Mechanistic studies revealed that, miR-106b-5p has an activating effect on Wnt/ß-catenin signalling. miR-106p-5p overexpression simultaneously targets multiple negative regulators of the Wnt/ß-catenin pathway, namely, LZTFL1, SFRP1 and DKK2. In addition, we also confirmed that miR-106b-5p and its targets expression correlates with the overall-survival of ccRCC patients from TCGA. CONCLUSIONS: These findings suggest that miR-106b-5p mediates the constitutive activation of Wnt/ß-catenin signalling, likely serving as a potential therapeutic target for ccRCC.

[Clinical observation on electric heat needle therapy for treatment of gonarthritis].

OBJECTIVE: To observe clinical therapeutic effect of electric heat needle therapy on senile gonarthritis. METHODS: Sixty-five patients were divided into a treatment group and a control group. The treatment group of 35 cases were treated by electric heat needling at Dubi (ST 35), Neixiyang (EX-LE 4), Yanglingquan (GB 34) and Yin-lingquan (SP 9), and the control group of 30 cases by simple acupuncture at the same acupoints as in the treatment group. In the two groups, the treatment was given once every other day, 10 sessions constituting one therapeutic course. After treatment of 2 courses, their therapeutic effects were compared. RESULTS: There was a very significant difference between the two groups in the total effective rate (P < 0.01). CONCLUSION: Electric heat needle therapy has a better clinical therapeutic effect on senile gonarthritis, better than simple acupuncture therapy.