Long non-coding RNAs have recently emerged as important regulators in the pathogenesis and progression of cancers. The long non-coding RNA urothelial carcinoma-associated 1 is reportedly upregulated and functions as an oncogene in some tumors. However, the role of urothelial carcinoma-associated 1 in renal cell carcinoma is not well elucidated so far. In this study, we found that urothelial carcinoma-associated 1 was overexpressed in renal cell carcinoma tissues compared with the adjacent normal tissues, and higher urothelial carcinoma-associated 1 expression levels were positively associated with advanced tumor stage and poor survival time in renal cell carcinoma patients. Further studies showed that knockdown of urothelial carcinoma-associated 1 suppressed renal cell carcinoma cell proliferation and S-phase cell number in vitro. Moreover, urothelial carcinoma-associated 1 was found to be associated with enhancer of zeste homolog 2, which suppressed p21 expression through histone methylation (H3K27me3) on p21 promoter. We also showed that knockdown of urothelial carcinoma-associated 1 increased the p21 protein expression through regulating enhancer of zeste homolog 2. In addition, bioinformatics analysis and dual-luciferase reporter assays confirmed that miR-495 was a target of urothelial carcinoma-associated 1 in renal cell carcinoma, and urothelial carcinomaassociated 1 promoted cell proliferation by negatively regulating miR-495. These findings illuminated that urothelial carcinoma-associated 1 promoted renal cell carcinoma progression through enhancer of zeste homolog 2 and interacted with miR-495. Overall, overexpression of urothelial carcinoma-associated 1 functions as an oncogene in renal cell carcinoma that may offer a novel therapeutic target for renal cell carcinoma patients. KeywordsRenal cell carcinoma, urothelial carcinoma-associated 1, enhancer of zeste homolog 2, miR-495, tumor proliferation Long non-coding RNAs (lncRNAs), that are more than 200 bases in length, consist of exons and introns in structure, without ORFs, and are not highly conserved. Recent reports suggest that lncRNAs play an important role in regulation of diverse cellular processes such as cell growth and apoptosis and cancer metastasis. 5 Several lncRNAs have been reported to be participated in renal cancer, such as, Qiao et al. 6 found that a decrease in lncRNA growth arrest-specific 5 (GAS5) expression was associated with RCC genesis and progression and overexpression of GAS5 can inhibit the RCC progression. A recent study indicated that LncRNA metastasis-associated lung adenocarcinoma transcription 1 (MALAT1) could function as a competing endogenous RNA to regulate zinc finger e-box binding homeobox 2 (ZEB2) expression by sponging miR-200s in clear cell kidney carcinoma. 7 HOX transcript antisense RNA (HOTAIR) was overexpressed in RCC, and knockdown of HOTAIR led to the weakening of the recruitment and binding abilities of enhancer of zeste homolog 2 (EZH2) and H3K27me3 locus with lncRNA HOTAIR and inhibited cell prol...
Abstract. Raf kinase inhibitory protein (RKIP) regulates multiple cellular processes, and its downregulation is associated with distinct human cancers. In the present study, the status of RKIP promoter methylation, as well as its expression and clinical significance in esophageal squamous cell carcinoma (ESCC), were examined. The promoter methylation status in the 5'-CpG island of the RKIP gene and the expression level of the RKIP protein were examined using a modified methylation-specific polymerase chain reaction (MSP) method and immunohistochemical staining, respectively, in 77 ESCC samples and matched paratumor normal tissues. The incidence of RKIP promoter methylation was significantly higher in tumor samples (75.3%) than in the matched normal tissues (27.3%; P<0.001). A higher incidence of promoter methylation was also detected in poorly differentiated cancers (93.5%) compared with well-differentiated cancers (50.0%; P<0.001), as well as in tumor samples with positive lymph node metastasis (86.7%) compared with those with negative lymph node metastasis (59.4%; P<0.001). Consistent with the promoter methylation status, the expression level of RKIP was significantly reduced in cancer tissues (36.4%) compared with matched normal tissues (76.6%; P<0.01), as well as in cancers with positive lymph node metastasis (24.4%) compared with those with negative lymph node metastasis (53.1%; P=0.01). Promoter methylation-induced gene silencing significantly correlated with the down regulation of RKIP and the development of ESCC. The results of the present study suggested that the methylation status of the RKIP promoter, when combined with its expression level, may serve as a biomarker for predicting the biological behaviors of ESCC.
General Secretary Xi attaches great importance to the construction and development of ideological and political courses in colleges and universities and puts forward the "big ideological and political" concept. Based on the local reality, this paper combines the spiritual strength shown in the struggle of people on Mayi Island, proposes that Mayi Island is an important classroom for "big ideological and political courses" and the spirit of Mayi Island needs to be carried forward and inherited in ideological and political courses in colleges and universities, and also explores the main paths to construct the "big ideological and political" classroom of Mayi Island such as establishing a new concept of practical education, basing on the traditional theoretical classroom, and creating a "mobile ideological and political classroom".
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