Clear Renal Cell Carcinoma Tissues Research Articles

MiR-340 regulates the growth and metabolism of renal cell carcinoma cells by targeting frizzled class receptor 3.

MicroRNA(miR)-340 is known as a multifunctional miRNA related to various types of cancer while its role in renal cell carcinoma (RCC) remains to be further investigated. In the present study, an apparent increase in miR-340 expression was observed in both clear cell RCC tissues and RCC cell line 786-O and Caki-1. Functionally, the overexpression of miR-340 promoted cell proliferation, migration, invasion, extracellular alanine(Ala) level, and glycolysis level in 786-O cells. Then, frizzled class receptor 3 (FZD3) was determined as the target gene of miR-340 and its expression level was negatively regulated by miR-340. The FZD3 silencing abrogated the inhibitory effect of miR-340 knockdown on cell proliferation, migration, invasion, Ala level, and glycolysis level in 786-O cells. In conclusion, miR-340 promotes proliferation, migration, and invasion of RCC cells via suppressing FZD3 expression, and the promotion effect of miR-340 on RCC progression may be due to its regulatory effect on glycolysis and Ala level.

RETRACTED: Oncogenic miR-27a delivered by exosomes binds to SFRP1 and promotes angiogenesis in renal clear cell carcinoma

Exosomes derived from cancer cells have emerged as important mediators of malignant phenotypes of tumors, being involved in the transmission of biological signals between cells. Herein, we intended to clarify the role of exosome-mediated transfer of oncogenic microRNA-27a (miR-27a) in angiogenesis of renal clear cell carcinoma (RCCC). Through bioinformatics analysis, we identified the differentially expressed genes of RCCC and predicted miRNAs targeting SFRP1. We manipulated the expression of miR-27a and/or SFRP1 in RCCC cells to explore their roles in angiogenesis through Cell Counting Kit-8 (CCK-8), Transwell, and Matrigel tubule formation assays. miR-27a loaded in exosomes was overexpressed and downregulated in vitro and in vivo to verify its effect on angiogenesis. SFRP1 was poorly expressed and miR-27a was highly expressed in RCCC tissues, showing a negative correlation. Dual-luciferase assay verified that miR-27a targeted and downregulated SFRP1 expression. Notably, miR-27a enhanced angiogenesis by downregulating SFRP1 expression. miR-27a-loaded exosomes can be delivered from RCCC cells to human umbilical vein endothelial cells (HUVECs). In vitro and in vivo experiments substantiated that miR-27a-loaded exosomes from RCCC cells repressed SFRP1, augmenting the viability, migration, and angiogenesis of RCCC cells. Together, RCCC-derived miR-27a-loaded exosomes inhibit SFRP1 expression and accelerate tumor angiogenesis in RCCC.

Expression and Prognostic Significance of Cadherin 4 (CDH4) in Renal Cell Carcinoma.

BackgroundAberrant expression of cadherin family members and their possible biological function have been widely studied in renal cell carcinoma (RCC). However, the expression of cadherin 4 (CDH4) and its value in RCC diagnosis and prognosis remains elusive.Material/MethodsThe TCGA database was used to analyze the expression of CDH4 and its clinical parameters and prognosis in 891 RCC patients. In addition, real-time PCR was used to verify the transcription of CDH4 in renal clear cell carcinoma tissue, and the distribution of protein was observed by immunohistochemical staining.ResultsWe found that the mRNA level of CDH4 was elevated in primary RCC in contrast with normal kidney samples using bioinformatics analysis based on the TCGA database. Among the 3 main subtypes of RCC, transcriptional CDH4 was significantly increased in KIRC and KIRP, while it was downregulated in KICH. Interestingly, CDH4 mRNA gradually decreased with the progression of KIRC and KIRP. The transcription of CDH4 in the primary tumor of KIRP patients at T3–T4 stages and KIRC patients with lymph node and distant metastasis were decreased significantly. Overall survival (OS) showed that KIRC and KICH patients with lower expression of CDH4 had worse outcomes.ConclusionsThe transcriptional level of CDH4 may serve as an effective diagnostic and prognostic biomarker for RCC patients.

Comprehensive profiling of circRNAs and the tumor suppressor function of circHIPK3 in clear cell renal carcinoma

Increasing evidence has indicated that circular RNAs (circRNAs) play a key role in the development and progression of diverse cancers, but their role in clear cell renal carcinoma (CCRCC) tumorigenesis is not well understood. In this study, we firstly performed comprehensive circRNA-seq from CCRCC tissues and pair-matched adjacent normal tissues. In total, 1184 circRNAs were dysregulated in human CCRCC tissues compared with those in adjacent normal tissues. We randomly selected four circRNAs, including circHIPK3 (circBase ID: hsa_circ_0000284), to test the circRNA-seq data in another 40 CCRCC tissues by quantitative real-time PCR (qRT-PCR). Furthermore, we found that circHIPK3 was downregulated in CCRCC tissues and cell lines. Overexpression of circHIPK3 effectively suppressed CCRCC cell invasion and migration in vitro, and inhibited CCRCC cell proliferation in vitro and in vivo. Moreover, bioinformatic analysis and luciferase reporter assay showed that circHIPK3 targeted miR-637 in CCRCC cells. Hence, CircHIPK3 may represent a tumor suppressor and target miR-637 in clear cell renal carcinoma.

Long Non-Coding RNA PANTR1 is Associated with Poor Prognosis and Influences Angiogenesis and Apoptosis in Clear-Cell Renal Cell Cancer.

POU3F3 adjacent non-coding transcript 1 (PANTR1) is an oncogenic long non-coding RNA with significant influence on numerous cellular features in different types of cancer. No characterization of its role in renal cell carcinoma (RCC) is yet available. In this study, PANTR1 expression was confined to human brain and kidney tissue and was found significantly up-regulated in clear-cell renal cell carcinoma tissue (ccRCC) compared to non-cancerous kidney tissue in two independent cohorts (p < 0.001 for both cohorts). In uni- and multivariate Cox regression analysis, ccRCC patients with higher levels of PANTR1 showed significantly poorer disease-free survival in our own respective cohort (n = 175, hazard ratio: 4.3, 95% confidence interval: 1.45–12.75, p = 0.008) in accordance with significantly poorer overall survival in a large The Cancer Genome Atlas database (TCGA) cohort (n = 530, hazard ratio: 2.19, 95% confidence interval: 1.59–3.03, p ≤ 0.001). To study the underlying cellular mechanisms mediated by varying levels of PANTR1 in kidney cancer cells, we applied siRNA-mediated knock-down experiments in three independent ccRCC cell lines (RCC-FG, RCC-MF, 769-P). A decrease in PANTR1 levels led to significantly reduced cellular growth through activation of apoptosis in all tested cell lines. Moreover, as angiogenesis is a critical driver in ccRCC pathogenesis, we identified that PANTR1 expression is critical for in vitro tube formation and endothelial cell migration (p < 0.05). On the molecular level, knock-down of PANTR1 led to a decrease in Vascular Endothelial growth factor A (VEGF-A) and cell adhesion molecule laminin subunit gamma-2 (LAMC2) expression, corroborated by a positive correlation in RCC tissue (for VEGF-A R = 0.19, p < 0.0001, for LAMC2 R = 0.13, p = 0.0028). In conclusion, this study provides first evidence that PANTR1 has a relevant role in human RCC by influencing apoptosis and angiogenesis.

COEXISTENCE OF CD44 AND KI-67 AS THE PROGNOSTIC MARKERS IN RENAL CELL CARCINOMA

Objective: An important feature of renal cell carcinoma (RCC) is its changeable prognosis. In recent years, several potential biomarkers have been investigated and confirmatory studies of these promising biomarkers are necessary to improve the clinical practice. In the present study, it was aimed to investigate the prognostic significance of CD44 expression by comparing it with Ki-67 and p53 in clear cell RCC.Material and Methods: Formalin- fixed, paraffin-embedded tissue sections of clear cell RCC from 34 patients, who had undergone radical or partial nephrectomy, were included in this study. Correlations between CD44, Ki-67 and p53 immunohistochemical expressions and clinicopathological parameters were determined.Results: CD44-high expression group (HEG) was significantly associated (p=0.035) and correlated (p=0.016, r=0.41) with a high nuclear grade. Similarly, the Ki-67-HEG was significantly associated (p=0.01) and correlated (p=0.01, r=0.436) with a high nuclear grade. We also found significant association (p&amp;lt;0.01) and correlation (p&amp;lt;0.01, r=0.621) between expressions of these markers. However, no antigen-antibody interaction was detected by p53 staining in clear cell RCC tissue sections.Conclusion: We concluded that increased expressions of CD44 and Ki-67 in tumour tissues predict an aggressive course of RCC patients.

Expression of human cartilage glycoprotein 39 in peripheral blood and tissues in renal cell carcinoma

Objective To investigate the expression of human cartilage glycoprotein 39 (YKL-40) in renal clear cell carcinoma and peripheral blood, and to analyze its correlation with prognosis. Methods A total of 110 patients who underwent radical nephrectomy were enrolled as the observation group, and 50 patients with normal physical examination results were enrolled as the control group. The renal clear cell carcinoma tissues and adjacent tissues were taken after operation, and the expression level of YKL-40 mRNA was detected by real-time fluorescent quantitative polymerase chain reaction (FQ-PCR). Results The level of YKL-40 [(186.9±15.7) μg/L] in the peripheral blood of the observation group before surgery was significantly higher than that of the control group [(115.1±12.5) μg/L] and after surgery [(146.3±13.5) μg/L, t=20.565, 28.478, P 0.05). Multivariate Cox analysis showed that Fuhrman classification [OR(95%CI): 2.335(1.359-10.656)], lymph node metastasis [OR(95%CI): 1.854(1.289-7.659)] and peripheral blood YKL-40 [OR(95%CI): 1.335(1.185-6.987)] were independent factors of OS (P<0.05). Conclusion The level of YKL-40 in peripheral blood of patients with renal clear cell carcinoma is elevated and closely related to OS, which may be a prognostic marker. There was no increase in the level of YKL-40 in cancer tissues, and serum YKL-40 may not be derived from cancer cells. Key words: YKL-40; Renal clear cell carcinoma; Overall survival

Correlation analysis between CXC chemokine receptor 6 and prognosis of renal clear cell carcinoma

Objective To investigate the correlation between CXC chemokine receptor 6 (CXCR6) and prognosis of renal clear cell carcinoma. Methods A total of 100 patients with renal clear cell carcinoma who underwent surgery in the First People's Hospital of Ziyang from January 2013 to October 2014 were selected. Immunohistochemistry was used to detect the expression of CXCR6 in 100 cases of renal clear cell carcinoma and adjacent normal tissues. The patients were followed up to observe the positive rate of CXCR6 expression and the factors affecting overall survival (OS) and progression-free survival (PFS) of renal clear cell carcinoma and adjacent normal tissues. Results The positive rate of CXCR6 expression in renal clear cell carcinoma tissues was higher than that in adjacent tissues, and the difference was statistically significant [46.0% (46/100) vs. 20.0% (20/100), χ2 = 15.287, P < 0.01]. The positive expression rate of CXCR6 in patients with clinical stage Ⅲ-Ⅳ, lymph node metastasis and pathological grade Ⅲ-Ⅳ was higher than that in patients with clinical stage Ⅰ- Ⅱ, pathological grade Ⅰ- Ⅱ and without lymph node metastasis, and the difference was statistically significant (all P < 0.05). A total of 92 patients were followed up and 40 died. The follow-up time reached to (35-60) months and the median follow-up time was 48.9 months. Kaplan-Meier and log-rank test showed that patients with positive CXCR6 expression had lower 3-year OS and PFS rate compared with patients with negative CXCR6 expression, and the difference was statistically significant (3-year OS rate: 52.1% vs. 78.6%, χ2 = 10.027, P = 0.001; 3-year PFS rate: 48.3% vs. 67.8%, χ2 = 4.344, P = 0.037). Cox regression multivariate analysis showed pathological grade (OS: OR = 2.154, 95% CI 1.547-9.517, P = 0.023; PFS: OR = 1.235, 95% CI 1.109-5.917, P = 0.042), lymph node metastasis (OS: OR = 1.412, 95% CI 1.109-5.917, P = 0.041; PFS: OR = 1.841, 95% CI 1.354-8.994, P = 0.010), CXCR6 expression (OS: OR = 1.864, 95% CI 1.358-6.813, P = 0.031; PFS: OR = 1.457, 95% CI 1.127-6.884,P = 0.025) were independent risk factors of OS and PFS for renal clear cell carcinoma patients treated by the surgery. Conclusions The positive expression of CXCR6 is an independent risk factor for OS and PFS of renal clear cell carcinoma. The prognosis of patients with positive CXCR6 expression is poor. Key words: Carcinoma, renal cell; Receptors, chemokine; Prognosis

The Role of Serine Peptidase Inhibitor Kazal Type 13 (SPINK13) as a Clinicopathological and Prognostic Biomarker in Patients with Clear Cell Renal Cell Carcinoma.

BackgroundThe serine peptidase inhibitor Kazal type 13 (SPINK13) gene has tumor suppressor activity, but its role in renal cell carcinoma (RCC) remains unknown. This study aimed to investigate mRNA expression of SPINK13 in clear cell renal cell carcinoma (CCRCC) in human tissue and to use bioinformatics data to investigate the role of SPINK13 expression as a clinicopathological and prognostic biomarker for patients with CCRCC.Material/MethodsPatients with CCRCC (N=533) with available RNA sequence data from The Cancer Genome Atlas (TCGA)-CCRCC database were analyzed with patients who had a tissue diagnosis of CCRCC (N=305) at the Fudan University Shanghai Cancer Center (FUSCC). Differential transcriptional and proteome expression profiles were obtained from the ONCOMINE cancer microarray database, TCGA, and the Human Protein Atlas (HPA) database. Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) measured SPINK13 mRNA expression in 305 samples of CCRCC tissue from the FUSCC. The effects of clinicopathological parameters on progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier and log-rank test.ResultsTranscriptional and proteome expression of SPINK13 were significantly increased CCRCC tissue samples. Increased SPINK13 mRNA expression was significantly associated with reduced PFS and OS in 838 patients with CCRCC patients from the two independent cohorts, the FUSCC and the TCGA-CCRCC cohorts (p<0.01). Gene set enrichment analysis (GSEA) showed that SPINK13 expression was involved in complement, apical junction, epithelial-mesenchymal transition (EMT), glycolysis, hypoxia, and inflammation signaling pathways.ConclusionsIncreased expression of SPINK13 was associated with poor prognosis in patients with CCRCC.

Decreased expression of TXNIP predicts poor prognosis in patients with clear cell renal cell carcinoma.

Accumulating evidence has demonstrated that thioredoxin interacting protein (TXNIP) is abnormally expressed in a variety of malignant tumors and functions as a tumor suppressor. However, the association between TXNIP and clear cell renal cell carcinoma (CCRCC) has not yet been fully elucidated. The aim of the present study was to evaluate the role of TXNIP in CCRCC using The Cancer Genome Atlas (TCGA) database. The RNA sequencing data and corresponding clinical data were collected from TCGA database. The association between TXNIP and patient clinicopathological characteristics was analyzed using analysis of variance and logistic regression. The Kaplan-Meier method and Cox proportional hazards model were used to assess the association between TXNIP and overall survival. Gene Set Enrichment Analysis (GSEA) was used to explore the associated signaling pathways. TXNIP expression was identified to be decreased in CCRCC tissues compared with normal tissues. The decreased expression of TXNIP in CCRCC was significantly associated with clinical stage [OR=0.509 for III vs. I (P=0.002); OR=0.527 for IV vs. I (P=0.012)], T stage [OR=0.552 for T3 vs. T1 (P=0.002)] and grade [OR=0.261 for G4 vs. G1 (P=0.027)]. Kaplan-Meier survival analysis indicated that cases of CCRCC with low TXNIP expression were associated with poorer prognoses compared with those with a high expression level (P=0.002). Univariate and multivariate Cox analyses indicated that TXNIP was an independent prognostic factor in CCRCC. GSEA revealed that 6 pathways exhibited significant differential enrichment in the TXNIP high-expression phenotype, including the WNT signaling pathway, the mitogen-activated protein kinase (MAPK) signaling pathway, the phosphatidylinositol signaling system, the transforming growth factor-β (TGF-β) signaling pathway, autophagy and the Janus kinase (JAK)-STAT signaling pathway. Taken together, the results of the present study indicate that TXNIP expression may be a potential prognostic marker for patients with CCRCC. In addition, the WNT signaling pathway, MAPK signaling pathway, phosphatidylinositol signaling system, TGF-β signaling pathway, autophagy and the JAK-STAT signaling pathway may be the crucial pathways regulated by TXNIP in CCRCC.

Construction and analysis of circular RNA molecular regulatory networks in clear cell renal cell carcinoma.

Increasing evidence has indicated that circular (circ)RNAs participate in carcinogenesis; however, the specific regulatory mechanisms underlying the effects of circRNAs, microRNAs (miRNAs/miRs) and genes on the development of clear cell renal cell carcinoma (CCRCC) remain unclear. In the present study, RNA microarray data from CCRCC tissues and control samples were downloaded from the Gene Expression Omnibus and The Cancer Genome Atlas, in order to identify significantly dysregulated circRNAs, miRNAs and genes. The Cancer-Specific circRNA Database was used to explore the interactions between miRNAs and circRNAs, whereas TargetScan and miRDB were employed to predict the mRNA targets of miRNAs. Functional enrichment and prognostic analyses were conducted in R. The results revealed that 324 circRNAs were downregulated, whereas 218 circRNAs were upregulated in cancer. In addition, a circRNA-miRNA-mRNA interaction network was constructed. Gene Ontology analysis of the upregulated genes revealed that these genes were enriched in biological processes, including ‘flavonoid metabolic process’, ‘cellular glucuronidation’ and ‘T cell activation’. The downregulated genes were mainly enriched in biological processes, such as ‘nephron development’, ‘kidney development’ and ‘renal system development’. The hub genes, including membrane palmitoylated protein 7, aldehyde dehydrogenase 6 family member A1, transcription factor AP-2α, collagen type IV α 4 chain, nuclear receptor subfamily 3 group C member 2, plasminogen, Holliday junction recognition protein, claudin 10, kinesin family member 18B and thyroid hormone receptor β, and the hub miRNAs, including miR-21-3p, miR-155-3p, miR-144-3p, miR-142-5p, miR-875-3p, miR-885-3p, miR-3941, miR-224-3p, miR-584-3p and miR-138-1-3p, were significantly associated with CCRCC survival. In conclusion, these results suggested that the significantly dysregulated circRNAs, miRNAs and genes identified in this study may be considered potential biomarkers of the carcinogenesis of CCRCC and the survival of patients with this disease.

Discovery of the expression of HK2 gene in clear cell carcinoma of the kidney and its clinical significance based on database analysis

Objective To analyze the association between hexokinase 2 (HK2) gene expression and clinical pathological characteristics in renal clear cell carcinoma using database and bioinformatics methods. Methods Oncomine database was used to analyze the most significant differentially expressed genes between renal clear cell carcinoma and non-kidney tissue. The expression levels of mRNA and protein were detected by GPEIA and The Human Protein Atlas database. Correlation of HK2 expression level between clinicopathological features and prognosis of renal clear cell carcinoma was analyzed using LinkedOmics and KM-plotter databases, respectively. The STRING database was used to predict the potential protein interaction mechanism. Results The most significant difference protein in renal clear cell carcinoma, i.e. HK2, was found, which was highly expressed in renal clear cell carcinoma tissues, and positively correlated with pathological stage, T stage and N stage of renal cell carcinoma (all P<0.05). The overall survival rate of the renal clear cell carcinoma patients with high expression of HK2 was significantly lower than that of the patients with low expression (P<0.05). Conclusions High expression of HK2 gene may be associated with pathological staging, high T stage, high N stage, and poor prognosis of renal clear cell carcinoma. Key words: Renal clear cell carcinoma; Hexokinase 2; Bioinformatics

Cytochrome C inhibits tumor growth and predicts favorable prognosis in clear cell renal cell carcinoma.

Cytochrome C (Cyto C), a multifunctional enzyme, has been demonstrated to be associated with cell apoptosis and respiration. Accumulating evidence has revealed that serum Cyto C is an effective indicator in evaluating the effect of chemotherapy. However, to the best of our knowledge, the clinical significance of Cyto C and its role in cell growth and apoptosis in clear cell renal cell carcinoma (CCRCC) remain unknown. In the present study, Cyto C expression was detected in 150 CCRCC and 30 normal tissues samples via immunohistochemistry. The results demonstrated that Cyto C protein expression levels in CCRCC tissues were downregulated compared with those in corresponding normal tissues. In addition, it was revealed that Cyto C expression was negatively associated with TNM stage. Further analyses revealed that patients with CCRCC and low Cyto C expression levels had a shorter survival time than those with high Cyto C expression. Multivariate analyses indicated that high Cyto C expression levels were an independent prognostic factor for survival. Functionally, overexpression of Cyto C effectively suppressed the growth of CCRCC cells and induced cell apoptosis, and knockdown of Cyto C reversed these effects. Finally, overexpression of Cyto C inhibited the tumor growth of CCRCC cells in vivo. Overall, the data of the present study indicated that Cyto C may be a novel prognostic biomarker and acted as a regulator of tumor growth in CCRCC.

Aberrant expression of vasculogenic mimicry, PRRX1, and CIP2A in clear cell renal cell carcinoma and its clinicopathological significance

Vasculogenic mimicry (VM) involves a tubular structure with a basement membrane that is similar to and communicates with vessels but functions independent of blood vessels to nourish tumor cells, promote tumor progression, invasion, and metastasis, with reduced 5-year survival rates. Tumor cell proliferation, invasion, and metastasis are promoted by the epithelial-mesenchymal transition (EMT). Paired-related homeobox 1 (PRRX1), a newly discovered EMT inducer, has been shown to correlate with metastasis and prognosis in diverse cancer types. Cancerous inhibitor of protein phosphatase 2A (CIP2A) was initially recognized as an oncoprotein. In this study, we aimed to investigate the expression and clinical significance of the EMT markers PRRX1, CIP2A and VM in clear cell renal cell carcinoma (CCRCC) and their respective associations with clinicopathological parameters and survival.Expression of PRRX1, CIP2A and VM in whole CCRCC tissues from 110 patients was analyzed by immunohistochemical and histochemical staining. Fisher's exact test or the chi square test was used to assess associations with positive or negative staining of these markers and clinicopathological characteristics.Positive expression of CIP2A and VM presence was significantly higher and that of PRRX1 was significantly lower in CCRCC tissues than in corresponding normal tissues. Furthermore, positive expression of CIP2A and VM was significantly associated with tumor grade, size, lymph node metastasis (LNM) stage, and tumor node metastasis (TNM) stage and inversely associated with overall survival time (OST). Moreover, levels of PRRX1 were negatively associated with tumor grade, size, LNM stage, and TNM stage. The PRRX1 subgroup had a significantly longer OST time than did the PRRX1 subgroup. In multivariate analysis, high VM and CIP2A, tumor grade, LNM stage, TNM stage, and low PRRX1 levels were identified as potential independent prognostic factors for OST in CCRCC patients.VM and expression of CIP2A and PRRX1 represent promising biomarkers for metastasis and prognosis and potential therapeutic targets in CCRCC.

Vimentin Overexpressions Induced by Cell Hypoxia Promote Vasculogenic Mimicry by Renal Cell Carcinoma Cells.

Vasculogenic mimicry (VM), the novel approach for tumor cells to obtain blood supply, was reported to be involved in antiangiogenic resistance and poor prognosis in renal cell carcinoma (RCC). However, the molecular mechanisms underlying VM formed by RCC cells are still not clearly depicted. In the present study, we found that OS-RC-2 acquired the VM forming ability accompanied with the increased expressions of Vimentin and AXL and decreased expression of E-Cadherin by CoCl2 treatment. Downregulation of Vimentin by siRNA severely impaired the capability of OS-RC-2 and 786-O to form VM structures induced by cell hypoxia in vitro. Moreover, knockdown of Vimentin inhibited cell migration and invasion, which could be prompted by hypoxia induction in RCC cells. In our clear cell RCC tissues, we found that VM was positively correlated with Vimentin overexpression and both predicted poor prognosis. In conclusion, Vimentin plays an important role in hypoxia induced VM formation of RCC cells and targeted Vimentin might be beneficial for RCC therapy.

High kinesin family member 11 expression predicts poor prognosis in patients with clear cell renal cell carcinoma

AimsKinesin family member 11 (Kif11) is a member of the kinesin family motor proteins, which is associated with spindle formation and tumour genesis. In this study, we investigated the relationship...

Lipophagy in nonliver tissues and some related diseases: Pathogenic and therapeutic implications.

Lipid autophagy (lipophagy) is defined as a selective autophagy process in which some intracellular lipid droplets are selectively degraded by autophagic lysosomes pathway. The occurrence of lipophagy was first discovered in liver tissues. Additionally, abundant evidence indicated that the occurrence of hepatic lipophagy has been implicated in many liver diseases including fatty liver diseases, nonalcoholic fatty liver diseases, liver fibrosis, and liver cirrhosis. However, recent studies suggested that hepatic lipophagy occurs not only in liver tissue but also in other nonliver tissues and cells. Furthermore, the occurrence of lipophagy plays a crucial role in nonliver tissues and some related diseases. For instance, lipophagy relieves insulin resistance in adipose tissue from obesity patient with type 2 diabetes. Additionally, lipophagy has the ability to remit neurodegenerative diseases by reducing activity-dependent neurodegeneration in nervous tissue. Lipophagy decreases muscle lipid accumulation and accordingly improves lipid storage myopathy in muscle tissue. Moreover, lipophagy alleviates the malignancy and metastasis of cancer in clear renal cell carcinoma tissue. Lipophagy is also involved in other processes, such as spermatogenesis, osteoblastogenesis, and mucosal ulceration. In conclusion, targeting lipophagy may be a critical regulator and a new therapeutic strategy for nonliver tissues and some related diseases.

Expression of pituitary transforming gene 1 in renal clear cell carcinoma and its association with prognosis

Objective To inyestigate the expression of pituitary transforming gene 1 (PTTG1) in renal clear cell carcinoma (RCCC) tissues and explore its association with the prognosis. Methods PTTG1 mRNA and protein levels were assessed in 41 paired RCCC tissues and adjacent normal tissues by real-time fluorescent quantitative polymerase chain reaction (FQ-PCR) and immunohistochemistry respectively. Further immunohistochemical analysis was implemented in 89 samples of RCCC to evaluate the associations between PTTG1 levels and the clinical characteristics in RCCC. Results FQ-PCR and immunohistochemical analysis demonstrated that the PTTG1 mRNA and protein levels were significantly higher in RCCC compared to normal tissues (P=0.007). In addition, the PTTG1 protein level in 89 RCCC samples was found to be significantly correlated with Fuhrman grade (P=0.026) and TNM stage (P=0.031), whereas it was not associated with gender (P=0.123), age (P=0.338) and recurrence (P=0.285). The five-year survival rate was 35.3% and 72.7% in patients with high and low PTTG1 levels respectively. The survival time of RCCC patients with high PTTG1 level was significantly lower than those with low PTTG1 1evel (P=0.029). Conclusion The overexpression of PTTG1 indicates a poor prognosis in RCCC patients and, therefore, PTTG1 may serve as a novel prognostic marker for RCCC. Key words: Pituitary transforming gene 1; Renal clear cell carcinoma; Survival rate; Prognosis

Expression and significance of Cystatin-C in clear cell renal cell carcinoma

PurposeCystatin-C (Cys-C) has been studied as a valuable prognostic indicator in several malignancies. The goal of this study is to explore the expression and prognostic significance of Cys-C in clear cell renal cell carcinoma (CCRCC). MethodsImmunohistochemistry and western blot assays were performed to evaluate the level of Cys-C expression in CCRCC tissue. Expression levels of Cys-C in CCRCC tissue samples in relation to clinicopathological characteristics of the tumors were assessed. Their prognostic significance was analyzed by univariate and multivariate analyses. In addition, the expression of Cys-C in 786-O cell lines was inhibited by using CRISPR/Case9 and the effects of Cys-C knockout on 786-O cells in vitro were evaluated using MTT method, colony formation assay, cell cycle assay, and cell migration and invasive assay. ResultsThe expression level of Cys-C was lower in CCRCC tissues (n = 253) than in paired adjacent non-cancerous tissues (n = 164) by immunohistochemistry (P < 0.001). Among the 253 patients, the results showed that patients with low Cys-C expression level in cancer tissue has longer overall survival (OS) than that with high Cys-C level. Furthermore, knockout of Cys-C in 786-O cell line has ability to suppress cell proliferation, induce G0/G1 phase arrest, inhibited cell invasion, decreased phosphorylation of ERK1/2, STAT-3 and enhanced phosphorylated JNK expression. ConclusionsA decrease in serum Cys-C is a favorable prognostic indicator for CCRCC patients. Inhibition of Cys-C suppressed RCC 786-O cell proliferation and invasion. These results indicated that Cys-C could serve as an ideal prognostic biomarker in patients with CCRCC.

Study on the mechanism behind lncRNA MEG3 affecting clear cell renal cell carcinoma by regulating miR-7/RASL11B signaling.

The goal of this research was to study the relationships between maternally expressed gene 3 (MEG3), microRNA-7 (miR-7), and RASL11B, and explore their influence on the progression of clear cell renal cell carcinoma (CCRCC). Microarray analysis was conducted using the data provided by The Cancer Genome Atlas. The expression levels of MEG3 and miR-7 in CCRCC and adjacent tissue samples were ascertained by quantitative real-time polymerase chain reaction (qRT-PCR). The cell proliferation activity was unmasked by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and cell apoptosis and cell cycle were investigated by flow cytometry. A dual luciferase reporter assay was used to verify target relationships. Wound healing assay and transwell assay were used to detect cell migration and invasion ability. Decreased MEG3 expression was observed in CCRCC tissues and cells. Overexpression of MEG3 accelerated apoptosis; inhibited cell proliferation, migration and invasion; and induced G0/G1 phase cell cycle arrest in CCRCC. MiR-7, directly binding to MEG3, was overexpressed in the CCRCC tissues and could inhibitthe apoptosis and promote the migration and invasion of CCRCC cells. RASL11B, lowly expressed in CCRCC, was a target of miR-7. After the overexpression of RASL11B, G0/G1 phase cell cycle arrest was induced; cell apoptosis was promoted; and the proliferation, invasion, and migration of CCRCC cells were inhibited. MEG3 could up-regulate RASL11B to inhibit the cell proliferation, invasion, and migration; induce G0/G1 cell cycle arrest; and promotecell apoptosis by suppressing miR-7 in CCRCC.