Single-cell RNA-sequencing analysis reveals MYH9 promotes renal cell carcinoma development and sunitinib resistance via AKT signaling pathway.

Clear cell renal cell carcinoma (ccRCC) is a serious threat to human health worldwide, while its heterogeneity limits therapeutic success and leads to poor survival outcomes. Single-cell RNA-sequencing (scRNA-seq) is an important technology, which provides deep insights into the genetic characteristics of carcinoma. In this study, we profiled the gene expression of single cells from human ccRCC tissues and adjacent normal tissues using the scRNA-seq. We found that MYH9 was commonly upregulated in the ccRCC cell subgroup. Additionally, MYH9 was of highly expression in ccRCC tissues and predicted poor prognosis of ccRCC patients. MYH9 knockdown in ccRCC cells dampened their proliferative and metastatic potentials, whereas MYH9 overexpression enhanced these properties. In vivo, MYH9 also promoted ccRCC growth. Mechanistic studies showed that MYH9 played these vital roles through AKT signaling pathway. Furthermore, MYH9/AKT axis determined the responses of ccRCC cells to sunitinib treatment and might serve as a biomarker for sunitinib benefits in ccRCC patients. Thus, MYH9 might be a novel therapeutic target and prognostic predictor for ccRCC.

YBX1 promotes tumor growth by elevating glycolysis in human bladder cancer.

Aerobic glycolysis, also known as Warburg effect, is a key hallmark of cancers. The Y-box-binding protein 1 (YBX1) is a well-known oncoprotein implicated in multiple malignant phenotypes of cancers. Meanwhile, little is known about the oncogenic functions and mechanisms of YBX1 in bladder cancer. Based on gene set enrichment analysis (GSEA) of TCGA RNAseq data, we find that YBX1 was profoundly involved in the glycolysis part of glucose metabolism. Loss- and gain-of-function studies show that YBX1 can enhance glycolysis as revealed by expression of glycolytic enzymes, glucose uptake, lactate secretion and extracellular acidification rate (ECAR). Inhibition of glycolysis completely compromises the tumor-promoting effect of YBX1 on tumor growth. Mechanistically, YBX1 regulates the expression of c-Myc and HIF1α, which further upregulate glycolytic enzymes to facilitate glycolysis. Moreover, in vivo study further confirms that genetic silencing of YBX1 markedly attenuates tumor growth and this tumor-suppressive effect is largely dependent on reduced glycolysis. Taken together, these results, as a proof of principle, provide a novel insight into the oncogenic role of YBX1 in glycolysis and suggest the potential therapeutic strategy by targeting YBX1 in bladder cancer.

Oxymatrine inhibits proliferation of human bladder cancer T24 cells by inducing apoptosis and cell cycle arrest.

Oxymatrine has been shown to exert an antitumor effect on several types of cancer cells. However, the role of oxymatrine in bladder cancer has not yet been evaluated. The present study was designed to investigate the potential anti-proliferative effect of oxymatrine on bladder cancer T24 cells and the possible mechanisms involved. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to determine cell growth, and the cell morphology was examined using hematoxylin and eosin staining, wrights' staining and electron microscopy. The caspase-3 and survivin mRNA and protein levels were assessed using reverse transcription-quantitative polymerase chain reaction and western blot analysis, respectively. The expression of tumor protein p53 (p53), Bcl-2-associated X protein (Bax) and B-cell lymphoma 2 (Bcl-2) were analyzed using immunohistochemistry. Oxymatrine inhibited the proliferation of the T24 cells in a dose- and time-dependent manner. Oxymatrine also induced apoptosis and cell cycle arrest in the cells, in association with the upregulation of caspase-3 and Bax, and the downregulation of survivin, Bcl-2 and p53 expression. Overall, oxymatrine inhibits the proliferation of human bladder cancer cells by inducing apoptosis and cell cycle arrest via mechanisms that involve p53-Bax signaling and the downregulation of survivin expression.

Retroperitoneal teratoma causing ptosis: A case report.

The present study reports the case of a patient who had undergone unsuccessful hormone therapy for ocular myasthenia gravis 14-years prior to the current presentation. The diagnosis of ocular myasthenia gravis was once again confirmed by a neostigmine test and repeat nerve stimulation study. Computed tomography scans in an external institution revealed a retroperitoneal cystic tumor with calcification above the left adrenal gland. The tumor was removed via a transperitoneal laparoscopic resection and was diagnosed as a mature cystic teratoma upon pathological examination. A teratoma is a common form of germ cell tumor, but primary teratomas of the retroperitoneum are quite rare in the adult population. Post-operative observation of the patient showed resolution of the ptosis and improved movement of the eyeballs. The potential mechanism was unclear, but the patient's teratoma was mature and may have contained myoid cells with antigenicity for anti-acetylcholine receptor (anti-AchR), as has been established in the thymus. Therefore, the anti-AchR antibody may have been involved.

Serum C-reactive protein acted as a prognostic biomarker for overall survival in metastatic prostate cancer patients.

The aim of this study was to determine whether baseline serum C-reactive protein (CRP) levels were associated with overall survival in patients with metastatic prostate cancer in the Chinese population. A total of 135 patients with metastatic prostate cancer were retrospectively reviewed. Both Kaplan-Meier product-limit method and multivariable analysis by Cox regression model were used to assess the prognostic role of serum CRP levels on overall survival of patients with metastatic prostate cancer. There were 51 patients (37.8%) with higher values of baseline serum CRP levels (≥10 mg/L). Kaplan-Meier product-limit method and log-rank test showed that patients with high serum CRP level (≥10 mg/L) had significantly worse overall survival than those patients with normal serum CRP level (<10 mg/L) (P < 0.001). The multivariable analysis by Cox regression model further showed that high serum CRP level (≥10 mg/L) was a significantly independent predictor of overall survival (hazard ratio (HR) = 2.39; 95% confidence interval (95% CI) 1.56-2.39, P < 0.001). In addition, high Gleason score (≥8) also was an independent predictor of overall survival (HR = 1.80; 95% CI 1.16-2.79, P = 0.008). In conclusion, serum CRP level is useful to predict the prognosis of metastatic prostate cancer patients, and high serum CRP level is a significantly independent predictor of worse overall survival.

Expression of nerve growth factor in the prostate of male rats in response to chronic stress and sympathetic denervation.

Nerve growth factor (NGF) has been found in the normal prostate of the Wistar rat and is regarded as an important prostatic mitogen. We have previously shown that chronic stress induced epithelial hyperplasia while sympathetic denervation caused atrophy in the male Wistar rat prostate. NGF may have been a contributing mechanism to the hyperplasia and atrophy response that was observed. The aim of the present study was to investigate the expression of NGF in the prostate of the male rat in response to chronic stress and denervation. Two weeks of restraint water-immersion stress were used to induce a chronic stress model in Wistar rats. Denervation of the peripheral sympathetic nerve was induced by 6-hydroxydopamine. The expression levels of NGF in the dissected prostate lobes were examined by immunohistochemistry. After 14 days of stress, proliferation of the epithelium in the ventral lobes was observed, whereas the dorsolateral lobes were almost unaffected. NGF immunoreactive protein was localized to the columnar secretory epithelium lines of the prostate tissue. Stress and denervation led to an increase in NGF expression in the ventral lobes. In conclusion, NGF was involved in the hyperplasia and atrophy in the prostate of the male rat in response to chronic stress and sympathetic denervation, and thus may be a contributing factor in the pathophysiology of the prostate.