BackgroundRenal cell carcinoma (RCC) is one of the common malignant tumors in the urinary system, which endangers human health for a long time. The past decade, the molecular biology of renal cell carcinoma has made considerable progress, so that we have a more profound understanding of renal cell carcinoma. Molecular biological mechanism of renal cell carcinoma remains to be explored. Evidence indicates that long non-coding RNAs (lncRNAs) may be important players in human cancer progression, including RCC. In this study, we found that a newly discovered pseudogene-derived lncRNA named DUXAP8, a 2107-bp RNA, was remarkably upregulated in RCC.Material/MethodsExpression of lncRNA DUXAP8 was determined by a qRT-PCR assay in RCC tissues. The proliferation and invasion of RCC cell were measured by a cell proliferation assay and a Transwell invasion assay. Expression of miR-126 was detected by real-time PCR. Interactions between lncRNA DUXAP8 and miR-126 were measured by a luciferase reporter assay and an RNA-pull down assay. In vivo experiments were used to detect tumor formation.ResultsTogether, our study not only identifies lncRNA DUXAP8 as a negative regulator of renal cancer with potential clinical value, but also reveals a regulatory mechanism by long non-coding RNAs to control tumor development.ConclusionsResults from this study provide evidence that lncRNA DUXAP8 enhances renal cell carcinoma progression via downregulating of miR-126, which offers a new approach for the treatment of RCC.

We explored the roles and regulatory mechanisms of the circular RNA (circRNA) nuclear receptor-interacting protein 1 (NRIP1; circNRIP1) in ACHN and CAKI-1 cells. ACHN and CAKI-1 cells were transfected with smallinterfering-circNRIP1 (si-circNRIP1) and microRNA-505 (miR-505) inhibitor or the corresponding controls. Cell viability was detected with the Cell Counting Kit-8. The protein expression levels of Bcl-2, Bax, cleaved-caspase-3, matrix metalloproteinase (MMP)-2, MMP-9, adenosine 5′-monophosphate (AMP)activated protein kinase (AMPK), protein kinase B (AKT), phosphatidylinositol 3-kinase (PI3K), and mammalian target of rapamycin (mTOR) were individually determined via Western blot. Quantitative reverse transcription polymerase chain reaction was used to examine the expressions of circNRIP1 and miR-505 both in tumor cells and tissues. The apoptotic rate, the colony numbers, and the migration rate were separately determined by the Annexin V-fluorescein isothiocyanate/propidium iodide and flow cytometer, colony formation assay, and migration assay. We found that circNRIP1 was overexpressed in tumor tissue but miR-505 was overproduced. Silencing circZNF292 induced inhibition of cell viability, colony formation, and migration, as well as the activity of AMPK and PI3K/AKT/mTOR cascades but enhancement of apoptosis. si-circNRIP1 stimulated the upregulation of miR-505, whose silence abolished the effects of si-circNRIP1 on these elements mentioned above. In conclusion, the circNRIP1 played oncogenic roles in the ACHN and the CAKI-1 cell lines by targeting miR-505 via stimulating AMPK and PI3K/AKT/mTOR cascades.

Acute kidney injury (AKI), a kind of syndrome with sudden degradation of renal function, is characterized by loss of urine creatinine. 1 With 7.0% incidence in China, AKI becomes a representative public health matter that ranges from newborns to senior citizens. 2 AKI is divided into pre-kidney, intrinsic and post-kidney, of whose pathophysiology risk factors include inflammatory diseases, 3 traumatism 4 and drug overdose. 5 In addition, ischaemia/reperfusion (I/R) during kidney transplantation also is extremely likely to elicit AKI. 6,7 I/R injury, which results from the inadequate supply of oxygen and nutrients to kidney Abstract Circular RNA YAP1 (circYAP1) was reported to participate in progression of gastric cancer. However, the role of circYAP1 in acute kidney injury (AKI) remains obscure.We attempted to examine the effects of circYAP1 on ischaemia/reperfusion-stimulated renal injury. AKI model was established by treating HK-2 cells in ischaemia/ reperfusion (I/R) environment. CircYAP1 expression in blood of AKI patients and I/Rtreated HK-2 cells was evaluated via RT-qPCR. CCK-8, flow cytometry, ELISA and ROS assay were executed to test the impact of circYAP1 on cell viability, apoptosis, inflammatory cytokines and ROS generation. Bioinformatic analysis was executed to explore miRNA targets. The relativity between circYAP1 and miR-21-5p was verified by RT-qPCR and luciferase assay. The functions of miR-21-5p in I/R-triggered injury were reassessed. PI3K/AKT/mTOR pathway was detected by Western blot. Down-regulated circYAP1 was observed in AKI blood samples and I/R-treated HK-2 cells. CircYAP1 overexpression expedited cell growth and weakened secretion of inflammatory factors and ROS generation in I/R-disposed cells. Besides, we found circYAP1 could sponge to miR-21-5p. Interestingly, miR-21-5p overexpression overturned the repressive effects of circYAP1 on cell injury. Moreover, PI3K/AKT/mTOR pathway was activated by circYAP1 via inhibiting miR-21-5p. We demonstrated that circYAP1 activated PI3K/AKT/mTOR pathway and secured HK-2 cells from I/R injury via sponging miR-21-5p. K E Y W O R D S acute kidney injury, circular RNA YAP1, ischaemia/reperfusion, microRNA-21-5p, PI3K/AKT/ mTOR pathway

The objective of this study was to investigate the inhibitory effects of tanshinone OOA on human bladder cancer BOU-87 cells and the xenograft in nude mice. BOU-87 cells were treated with tanshinone OOA with concentration of 0.5, 1, 2 and 4 g/L. The cell proliferation, cycle and apoptosis were detected. The nude mice with BOU-87 cell xenograft were treated with normal saline (control), 5-fluorouracil (5-FU), 200, 400 and 600 mg/kg tanshinone OOA, respectively. The animal body weight and growth of tumor were measured. The expressions of B-cell lymphoma-2 (Bcl-2), Caspase-3 and proliferating cell nuclear antigen (PCNA) protein in xenograft were detected. The apoptosis index of cells was determined. Results showed that, tanshinone OOA inhibited the proliferation of BOU-87 cells, promoted their apoptosis, and arrested more cells in G 0 /G 1 phase. Tanshinone OOA significantly inhibited the growth of xenograft in nude mice and promoted the apoptosis of tumor cells in xenograft. Tanshinone OOA down-regulated Bcl-2 and PCNA expression and up-regulated Caspase-3 expression in xenograft. On conclusion, tanshinone OOA has inhibitory effects on human bladder cancer BOU-87 cells, and can inhibit the BOU-87 cells xenograft in nude mice.

Anti-T-lymphocyte globulin (ATG) is frequently used in the induction regimen of renal transplantation, but its dose has not been standardized. In the present study, the efficacy of different ATG-Fresenius (ATG-F) doses was assessed in recipients of renal transplantation. A total of 131 adult recipients of renal transplantation who received ATG-F induction between August 2015 and July 2018 were included. The incidence of biopsy-confirmed acute rejection, graft function, as well as graft and patient survival within 12 months post-transplant, was assessed, and adverse events, including hematologic and infection-associated side effects, were compared between patients receiving a cumulative ATG-F dose of <7 or ≥7 mg/kg. The incidence of biopsyconfirmed acute rejection was similar between patients receiving cumulative doses of <7 and ≥7 mg/kg (7.5 vs. 4.7%, P=0.766). The incidence of infection within 12 months was lower in the ATG-F <7 mg/kg group compared with that in the ≥7 mg/kg group (26.9 vs. 50.0%, P= 0.006), but the incidence of pneumonia did not differ between the ATG-F <7 and ≥7 mg/kg groups (10.4 vs. 20.3%, P= 0.117). The incidence of urinary infection was higher in the ≥7 mg/kg group than in the <7 mg/kg group (20.4 vs. 7.46%, P= 0.033), while the extent and duration of anemia and lymphopenia was similar between groups. There was no difference in graft function, delayed graft function, as well as overall and graft survival between the groups. In conclusion, a moderate reduction in the cumulative ATG-F dose was not associated with an increased risk of acute rejection, while the risk of infection was reduced. Optimization of the ATG-F dose for induction may facilitate the reduction of the risk of infection without compromising the induction efficacy in renal transplant recipients.