Transcriptomics analysis revealed that TAZ regulates the proliferation of KIRC cells through mitophagy.

Transcriptional Co-Activator with PDZ-Binding Motif (TAZ, also known as WWTR1) is a downstream effector of the Hippo pathway, involved in the regulation of organ regeneration and cell differentiation in processes such as development and regeneration. TAZ has been shown to play a tumor-promoting role in various cancers. Currently, many studies focus on the role of TAZ in the process of mitophagy. However, the molecular mechanism and biological function of TAZ in renal clear cell carcinoma (KIRC) are still unclear. Therefore, we systematically analyzed the mRNA expression profile and clinical data of KIRC in The Cancer Genome Atlas (TCGA) dataset. We found that TAZ expression was significantly upregulated in KIRC compared with normal kidney tissue and was closely associated with poor prognosis of patients. Combined with the joint analysis of 36 mitophagy genes, it was found that TAZ was significantly negatively correlated with the positive regulators of mitophagy. Finally, our results confirmed that high expression of TAZ in KIRC inhibits mitophagy and promotes KIRC cell proliferation. In conclusion, our findings reveal the important role of TAZ in KIRC and have the potential to be a new target for KIRC therapy.

The causal effect of serum micronutrients on malignant kidney neoplasm in European descent.

Purpose: Observational studies have revealed that serum minerals and vitamins are associated with cancer. However, the causal relationships between serum minerals and vitamins and renal malignancies remain unclear. Methods: Mendelian randomization (MR) was used for causal estimation. Single nucleotide polymorphisms (SNPs) for serum minerals and vitamins were obtained from published genome-wide association studies (GWAS). GWAS for malignant kidney neoplasm was obtained from the FinnGen consortium. Methods of inverse variance weighted (IVW), MR-Egger, and weighted median were carried out for causal inference. F-statistic was calculated to ensure a robust instrumental variable. Cochran's Q statistics was applied to calculate heterogeneity. MR-Egger regression, MR-pleiotropy residual sum and outlier methods (MR-PRESSO) methods were used to perform pleiotropy analysis. Meanwhile, confounding factors were considered to determine whether causal inference would be biased. Results: Eight different micronutrients were included (zinc, iron, magnesium, calcium, copper, selenium, phosphate, and vitamin B12). After MR analysis, we found a protective effect of serum zinc against malignant kidney neoplasm (IVW: odds ratios (ORs), 0.86; 95% confidence interval (95% CI), 0.78-0.94; p, 0.0016; MR-Egger: OR, 0.80; 95% CI, 0.64-0.97; p, 0.052; weighted median: OR, 0.85; 95% CI, 0.75-0.96; p, 0.011). Causal relationships between other micronutrients and malignant kidney neoplasm were not obtained. No heterogeneity and pleiotropy were detected, while causality was not biased by confounding factors. Conclusion: We considered that serum zinc exerted a protective effect against malignant kidney neoplasm. In clinical practice, for people with high malignant kidney neoplasm risk, an oral zinc supplementation might play a role in a potential therapeutic target.

Atractylenolide I inhibits EMT and enhances the antitumor effect of cabozantinib in prostate cancer via targeting Hsp27.

Objective: To investigate the effect of Hsp27 and the inhibitory effect of Atractylenolide I (ATL-1) on the proliferation of prostate cancer cell DU145 and PC-3. Methods: MTT assay was used to detect the inhibitory effect of silencing Hsp27 and ATL-1 on DU145 and PC-3 proliferation of prostate cancer cells. TUNEL detected the apoptosis rate of prostate cancer cell DU145 and PC-3 after silencing Hsp27 and ATL-1 treated. qRT-PCR was used to detect the changes of apoptosis related genes caspase-3, PARP, Bax and Bcl-2 in prostate cancer cell DU145 and PC-3 after the effect of silencing Hsp27 and ATL-1 treated. At the same time, the antitumor effect of ATL-1 combined with cabozantinib was analyzed. Results: Hsp27 was highly expressed in human prostate cancer. MTT assay showed that ATL-1 inhibited the proliferation of prostate cancer cells DU145 and PC-3 compared with the control group. TUNEL results showed that silencing Hsp27 and ATL-1 treated could significantly promote the apoptosis of prostate cancer cells DU145 and PC-3 compared with the control group. qRT-PCR results showed that compared with the control group, ATL-1 could promote the expression of caspase-3, PARP and Bax in DU145 and PC-3 prostate cancer cells. Inhibition of Hsp27 by ATL-1 reduced cell viability and induced apoptosis. ATL-1 inhibits the antitumor effect of Hsp27 - enhanced cabozantinib. Hsp27 regulates eIF4E and mediates cell protection. Conclusion: Silencing Hsp27 inhibits EMT. ATL-1 can inhibit the malignant evolution of prostate cancer cells by inhibiting Hsp27/eIF4E. ATL-1 also enhanced chemosensitization of cabozantinib in prostate cancer.

Evaluation of acridine orange fluorescence in exfoliative urinary cytology for diagnosing bladder carcinoma.

PURPOSE: This study reviewed acridine orange fluorescence (AO-F) in exfoliative urinary cytology results of 1,016 inpatients with urothelial cell carcinoma of the bladder and 804 outpatients to investigate the value of AO-F in the diagnosis of bladder cancer. METHODS: A total of 1,016 bladder cancer inpatients from October 1995 to October 2005 and 804 outpatients from January 2004 to January 2006 were enrolled in this study. Each patient provided the morning urine specimen of 30-50 ml in a sterile container. Urine sediments were stained by acridine orange and observed with a fluorescence microscope; 60 bladder cancer inpatients from January 2006 to July 2007 were also chosen for the control study of three different detection methods, including AO-F, hematoxylin and eosin and Feulgen staining. RESULTS: Of the 1,016 bladder carcinoma samples analyzed, 793 were AO-F positive. Total positive rate of AO-F was 78.05 %. The positive rate was 74.69 % (611/818) for non-muscle invasive bladder carcinoma and 91.91 % (182/198) for muscle invasive bladder carcinoma. A significant correlation of AO-F positivity with clinical stage was observed (P < 0.01). The positive rates among various pathological grades were 66.7 % (32/48) for G1, 67.5 % (319/474) for G2 and 90.4 % (413/457) for G3 with significant differences (P < 0.01). For the 804 outpatients, the sensitivity and specificity of bladder carcinoma were 77.11 and 85.29 %, respectively. CONCLUSIONS: With its high sensitivity and specificity, AO-F is superior to other detection methods for bladder carcinoma detection. In addition, it is familiar, non-invasive, quick, cheap and easily repeatable.

[Response of indica rice in two genic male-sterile lines to temperature and photoperiod].

Investigations on the fertility conversion of two photoperiod- and temperature sensitive genic male-sterile lines Zheda 247S and Peiai 64s under natural conditions in Hangzhou showed that there was a little impact of photoperiod on their fertility expression, while temperature was the main factor. Among daily mean temperature, daily maximum temperature and daily minimum temperature, the last one had the most significant correlation with the fertility. The temperature sensitive stage of Zheda 247S and Peiai 64S was 318 and 621 days before heading, the critical temperature of their fertility conversion was 25.28 and 25.66 degrees C, and the critical date was September 19th and September 25th, respectively. Compared to Peiai 64S, Zheda 247S had a more evident fertility conversion, its sterility was more complete and its self-setting percentage was higher at fertile stage, and the duration of the fertile stage was longer. Zheda 247S could be reproduced in Hangzhou.