Akt/protein kinase B (PKB) functions in conserved signaling cascades that regulate growth and metabolism. In humans, Akt/PKB is dysregulated in diabetes and cancer; in Caenorhabditis elegans, Akt/PKB functions in an insulin-like signaling pathway to regulate larval development. To identify molecules that modulate C. elegans Akt/PKB signaling, we performed a genetic screen for enhancers of the akt-1 mutant phenotype (eak). We report the analysis of three eak genes. eak-6 and eak-5/sdf-9 encode protein tyrosine phosphatase homologs; eak-4 encodes a novel protein with an N-myristoylation signal. All three genes are expressed primarily in the two endocrine XXX cells, and their predicted gene products localize to the plasma membrane. Genetic evidence indicates that these proteins function in parallel to AKT-1 to inhibit the FoxO transcription factor DAF-16. These results define two membrane-associated protein tyrosine phosphatase homologs that may potentiate C. elegans Akt/PKB signaling by cell autonomous and cell nonautonomous mechanisms. Similar molecules may modulate Akt/PKB signaling in human endocrine tissues.
Clear cell renal cell carcinoma (ccRCC) is a common malignancy, yet, the mechanisms underlying tumorigenesis remain unclear. Several miRNAs have been implicated in the development of RCC previously via regulation of target gene expression. As miR-625-3p has recently been identified to play a role in development of other malignancies and is reportedly upregulated in ccRCC, we sought to investigate the role of this miRNA in the progression of ccRCC. Analysis of 30 paired fresh ccRCC tissues and adjacent normal renal tissues revealed that the expression of miR-625-3p was increased in ccRCC tissues compared to normal tissues. Subsequently, in 136 formalin-fixed paraffin-embedded ccRCC tissues, the increased miR-625-3p expression was correlated with poor prognosis for ccRCC patients. The diagnostic value of miR-625-3p was identified in 50 ccRCC patients and 74 healthy controls by ROC curve. miR-625-3p was decreased in serum of ccRCC patients compared to healthy individuals. miR-625-3p could serve as a promising serum biomarker for yielding an area under the receiver operating characteristic curve of 0.792 with 70.3% sensitivity and 80.0% specificity in discriminating ccRCC from healthy individuals. Using in vitro functional assays, we found that overexpression of miR-625-3p promoted migration and invasion of ccRCC cells but reduced ccRCC cell apoptosis. Inhibition of miR-625-3p, on the other hand, exerted the opposite effects. Bioinformatic analyses indicated that predicted gene targets of miR-625-3p are correlated with lower overall survival of ccRCC patients. Together, these findings demonstrate that miR-625-3p promotes ccRCC migration and invasion and reduces apoptosis, providing a prognostic marker for survival and a potential diagnostic and therapeutic target against ccRCC.
OCTOBER: To explore the effects of the glucagon-like peptide 1 (GLP-1) liraglutide on the penile erectile function of rats with diabetic erectile dysfunction (DED) by observing the impact of liraglutide on the expression of eNOS in the corpus cavernosum of diabetic rats.We randomly divided 30 six-week-old male SD rats into a normal control (n = 10) and an experimental group (n = 20) , established models of diabetes mellitus (DM) in the experimental rats, and subdivided them into a DM (n = 8) and a GLP-1 group (n = 8) to receive intramuscular injection of normal saline and liraglutide at 5 mg per kg of the body weight per day, respectively. After 12 weeks of intervention, we obtained the levels of FPG, FINS, TG, TC, HDL-C, LDL-C, testosterone, and IL-6 and the indexes of Homa-IR and Homa-β, detected the expressions of Akt/p-Akt and eNOS/p-eNOS in the corpus cavernosum by Western blot, and compared the erectile function between different groups.The frequency and rate of penile erection were significantly lower in the DM group than in the GLP-1 and normal control groups (P < 0.05) and also lower in the GLP-1 group than in the normal controls (P < 0.05). Immunofluorescence staining showed the expression of eNOS mainly in the cytoplasm of the cavernosal vessels and sinusoidal endothelial cells, markedly lower in the DM and GLP-1 groups than in the normal rats (P < 0.05), but higher in the GLP-1 than in the DM group (P < 0.05). The level of eNOS/p-eNOS in the penile tissue was significantly decreased in the DM and GLP-1 groups in comparison with the normal controls (P < 0.01 or P < 0.05), while that of p-eNOS was markedly increased in the GLP-1 group as compared with the DM group (P < 0.05). No statistically significant differences were observed in the Akt level among the three groups of animals (P > 0.05). The expression of p-Akt was remarkably reduced in the DM and GLP-1 groups in comparison with the control rats (P < 0.01 or P < 0.05), but higher in the GLP-1 than in the DM group (P < 0.05).GLP-1 can protect the function of endothelial cells in the corpus cavernosum and improve the erectile function of DED rats by regulating the Akt/ eNOS signaling pathway, which indicates that GLP-1 could be an important option for the treatment and prevention of DED.
Renal cell carcinoma (RCC) is a common cancer that accounts for about 1.6% of all malignancies. Accumulating evidence has shown that miRNAs may play important roles in the development of cancers and that these same miRNAs may serve as diagnostic and prognostic biomarkers. The role of the miRNA miR-378a-5p in RCC, however, has been largely unexplored. In our study, we have demonstrated that miR-378a-5p expression was decreased in renal tissues and in RCC cell lines compared with corresponding expression levels in normal renal tissues and in the 293-T cell line. Functional studies in two RCC cell lines (ACHN and 786-O) have indicated that miR-378a-5p overexpression attenuated cell proliferation, migration, and invasion while promoting cell apoptosis. Inhibition of miR-378a-5p expression, on the other hand, promoted cell proliferation, migration, and invasion while reducing cell apoptosis. Additionally, in 42 cases of renal cancer formalin-fixed paraffin-embedded specimens, patients with higher expression levels of miR-378a-5p had significantly longer overall survival rates (P<0.05) than patients with lower miR-378a-5p expression levels. Thus, in this study, we have shown that miR-378a-5p can serve as a tumor suppressor and a potential prognostic biomarker in RCC.
Subsequently to the publication of the article, the authors have recognized a need to correct some of its content in order to clarify the accuracy of the article’s information. First, Dr Yongqing Lai should have been included as the joint corresponding author for this paper. Therefore, the information in the correspondence box (also including his email address) should have been as follows (changes are indicated in bold): Correspondence to: Professor Liangchao Ni and Dr Yongqing Tai, Department of Urology, Peking University Shenzhen Hospital, 1120 Lianhua Road, Shenzhen, Guangdong 518036, P.R. China E‑mail: lncord@163.com E‑mail: yqlord@163.com Secondly, the authors wished to add two new authors (Canbin Lin and Hang Li) to the paper. Note that all the existing authors agree to the addition of these new authors; therefore, the revised author list is as appears above (with the newly added authors appearing third and fourth in the author list), and the affiliations should have appeared as follows: YULIN LAI1,2,5*, JING QUAN1,3,5*, CANBIN LIN1,4,5, HANG LI1,5, JIA HU1,2, PEIJIE CHEN1,4,5, JINLING XU1,5, XIN GUAN1,5, WEIJIE XU1,5, YONGQING LAI1,5 and LIANGCHAO NI1,5 1Department of Urology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036; 2Graduate School, Guangzhou Medical University, Guangzhou, Guangdong 511436; 3Graduate School, Anhui Medical University, Anhui Hefei 230032; 4Graduate School, Shantou University Medical College, Shantou, Guangdong 515041; 5The Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Institute of Urology of Shenzhen PKU‑HKUST Medical Center, Shenzhen, Guangdong 518036, P.R. China *Contributed equally Lastly, the authors inadvertently omitted the reference number for the funding received from the ‘San‑ming’ Project of Medicine in Shenzhen: The ref. no. should have appeared as SZSM201612066. The authors regret that these errors and omissions were not corrected prior to the publication of the paper, and apologize to the readership for the inconvenience caused. [the original article was published in Experimental and Therapeutic Medicine Med 16: 436‑444, 2018; DOI: 10.3892/etm.2018.6151]
The aim of the present study was to investigate the role of microRNA (miR)‑222‑3p in renal cell carcinoma (RCC). The expression level of miR‑222‑3p was detected in RCC tissues and cell lines (ACHN, 786‑O, Caki‑1 and 769‑P) and was identified to be significantly upregulated compared with the level in adjacent normal renal tissues and HK‑2 cells. Further in vitro experiments demonstrated that the overexpression of miR‑222‑3p promoted the migration and invasion, and attenuated the apoptosis of 786‑O cells, whereas the knockdown of miR‑222‑3p suppressed the migration and invasion and induced the apoptosis of 786‑O cells. Similar results were observed in the ACHN cell line in terms of migration, invasion and apoptosis. Furthermore, the expression level of miR‑222‑3p was measured in 42 RCC formaldehyde‑fixed paraffin‑embedded samples, and the association between the expression of miR‑222‑3p and the pathological characteristics and overall survival rate of patients with RCC was analyzed. The results demonstrated that patients with a higher expression of miR‑222‑3p had a significantly lower overall survival rate, compared with those with a lower expression of miR‑222‑3p [hazard ratio (HR)=5.120; P=0.036]. Multivariate analysis identified that patients with a higher expression of miR‑222‑3p retained the statistically significant decrease in overall survival rate compared with patients with a lower expression of miR‑222‑3p (HR=5.636; P=0.030). Furthermore, Kaplan‑Meier survival curves indicated that patients with higher miR‑222‑3p had significantly lower overall survival rates compared with patients with lower miR‑222‑3p (P=0.020). Taken together, these results suggested that miR‑222‑3p serves as an onco‑miR in RCC and may be a potential prognostic biomarker and therapeutic target in patients with RCC.
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