Long non-coding RNA BRE-AS1 inhibits proliferation, migration and invasion of clear cell renal cell carcinoma by downregulating miR-106b-5p.

OBJECTIVE: The objective of this study was to investigate the involvement of the long non-coding RNA (lncRNA) BRE-AS1 in clear cell renal cell carcinoma (ccRCC) and to explore its potential therapeutic role. METHODS: The expression of BRE-AS1 and miR-106b-5p was determined by qRT-PCR. Overexpression of BRE-AS1 and miR-106b-5p were performed to study their relationship. Transwell assays were used to evaluate cell movement. Methylation-specific PCR (MSP) was performed to explore the role of BRE-AS1 in the methylation of the miR-106b-5p gene. RESULTS: The results showed that the expression levels of BRE-AS1 were decreased, while those of miR-106b-5p were increased in ccRCC tissues. BRE-AS1 was found to be closely associated with the prognosis of patients with ccRCC. The expression of BRE-AS1 was inversely correlated with that of miR-106b-5p in tumor tissues. Overexpression of BRE-AS1 led to decreased expression levels of miR-106b-5p and increased methylation of the miR-106b-5p gene, whereas miR-106b-5p did not affect the expression of BRE-AS1. BRE-AS1 inhibited the movement and proliferation of ccRCC cell lines, while miR-106b-5p suppressed the role of BRE-AS1. CONCLUSION: BRE-AS1 may suppress ccRCC by downregulating the expression of miR-106b-5p.

ROCK2-RNA interaction map reveals multiple biological mechanisms underlying tumor progression in renal cell carcinoma.

Renal cell carcinoma (RCC) is the most common form of kidney cancer in adults. Despite new therapeutic modalities, the outcomes for RCC patients remain unsatisfactory. Rho-associated coiled-coil forming protein kinase 2 (ROCK2) has previously been shown to be upregulated in RCC, and its expression was negatively correlated with patient survival. However, the precise molecular function of ROCK2 has remained unclear. Herein, using RNA-seq analysis of ROCK2 knockdown and control cells, we identified 464 differentially expressed genes, and 1287 alternative splicing events in 786-O RCC cells. Furthermore, mapping of iRIP-seq reads in 786-O cells showed a biased distribution at 5' UTR, intronic and intergenic regions. By comparing ROCK2-regulated alternative splicing and iRIP-seq data, we found 292 overlapping genes that are enriched in multiple tumorigenic pathways. Taken together, our work defined a complex ROCK2-RNA interaction map on a genomic scale in a human RCC cell line, which deepens our understanding of the molecular function of ROCK2 in cancer development.

Pioglitazone Ameliorates Renal Ischemia-Reperfusion Injury via Inhibition of NF-κB Activation and Inflammation in Rats.

Renal ischemia-reperfusion injury (IRI) is considered as a major cause of acute kidney injury. In this study, we investigated the role of the NF-κB signaling pathway and inflammation in the amelioration of renal IRI using pioglitazone. Sprague-Dawley (SD) rats were subjected to bilateral renal artery clamping for 45 min followed by perfusion restoration for establishing a simulated renal IRI model. At 24 h post-operatively, we assessed the serum levels of creatinine and urea nitrogen, expression levels of peroxisome proliferator-activated receptor gamma (PPAR-γ) and NF-κB-related (p-IKK-ß and IκB-α) proteins, and mRNA expression levels of the inflammatory cytokines, including TNF-α and MCP-1, in the renal tissue of various study groups. The histopathological evaluation of renal tissue was also conducted. In rat renal tissue, pioglitazone treatment decreased the serum levels of post-renal IRI creatinine and urea nitrogen, as well as necrosis. Furthermore, it elevated the expression of PPAR-γ protein and decreased the expression of NF-κB-related proteins. Pioglitazone also decreased the mRNA expression of TNF-α and MCP-1 in the renal tissue. Thus, pioglitazone ameliorates renal IRI by inhibiting the NF-κB signaling pathway and inflammatory response in rats.

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.

miR-27a in serum acts as biomarker for prostate cancer detection and promotes cell proliferation by targeting Sprouty2.

Prostate cancer (PCa) exhibits a high incidence among men, but there is no effective and non-invasive biomarker for the diagnosis of PCa, and the pathogenesis of PCa remains unclear. The present study identified that miR-27a was significantly overexpressed in the tumor tissues and sera of patients with PCa. In addition, high serum levels of miR-27a were correlated with poor survival in patients with PCa. Receiver-operating characteristic curves analysis demonstrated that the serum levels of miR-27a exhibited a high area under the curve value. Furthermore, miR-27a mimics or inhibitors significantly promoted or repressed the proliferation of PCa cells, respectively. In addition, it was identified that the expression of Sprouty2 (SPRY2) was inversely correlated with the expression of miR-27a in PCa tissues. The knockdown or overexpression of SPRY2 promoted or suppressed the proliferation of PCa cells, respectively, and the overexpression of SPRY2 inhibited the increased proliferation and cell cycle distribution of PCa cells mediated by miR-27a mimics. Taken together, these data indicated that the serum levels of miR-27a may be a novel and non-invasive biomarker for the diagnosis and prognosis of patients with PCa, and miR-27a/SPRY2 may be a therapeutic target for the treatment of PCa.

[Expression of lymphotactin in renal tuberculosis].

AIM: To study the expression of lymphotactin in normal kidney and renal tuberculosis and the arrangement of lymphotactin and infiltrating CD4(+) T cells and CD8(+) T cells in renal tuberculosis. METHODS: HLptn cDNA of tissues from six cases with normal kidneys and ten cases with tuberculous kidneys was amplified by RT-PCR. The RT-PCR products were separated with 2% of gel. The cDNA was cloned to vector pGM-T Easy and was completely sequenced. The immunohistochemical staining method was used to examine the expression of lymphotactin in normal kidneys and tuberculous kidneys and the expression of CD4 and CD8 in tuberculous kidneys. RESULTS: The sequence of cloned hLptn cDNA was confirmed and it was identical with the sequence of NO.U23772 published in GenBank. Both normal kidneys and tuberculous kidneys expressed hLptn mRNA. HLptn was detected not only in the cells of normal renal glomerulus and renal tubule but also in the cells of remaining renal glomerulus and renal tubule of tuberculous kidneys. The cells expressing surface antigens CD4 and CD8 scattered in granulomas. CONCLUSION: The constructive expression of hLptn is in the cells of renal glomerulus and renal tubule of normal kidney and tuberculous kidney. The accumulation of CD4(+) T cells and CD8(+) T cells in granulomas may not depend on hLptn.