bims-lorfki 2021-03-07 papers

Oncol Rep. 2021 Apr;45(4): 1-13

Ginsenoside compound K exerts antitumour effects in renal cell carcinoma via regulation of ROS and lncRNA THOR.

Shuqiu Chen, Haihong Ye, Fanger Gong, Suming Mao, Cong Li, Bin Xu, Yu Ren, Rui Yu.

Renal cell carcinoma (RCC) is a common type of kidney cancer that lacks effective therapeutic options. Ginsenoside compound K (CK), an active metabolite of ginsenosides, has been reported to induce apoptosis in various types of cancer cells. However, the effects of CK in RCC remain to be elucidated. Thus, the aim of the present study was to investigate the antitumor effects of CK on RCC cells. The effects of CK on the proliferation, migration, invasion, cell cycle and apoptosis of RCC cell lines (Caki‑1 and 768‑O) were investigated using MTT, wound healing, Transwell and flow cytometry assays, respectively. Changes in the expression levels of long non‑coding RNAs (lncRNAs) and proteins were measured via reverse transcription‑quantitative PCR and western blotting, respectively. Transfections with testis associated oncogenic (THOR) small interfering RNA and pcDNA were performed to knock down and overexpress lncRNA THOR, respectively. It was found that CK could effectively inhibit the proliferation, migration and invasion of RCC cells. CK also induced cell cycle arrest and caspase‑dependent apoptosis in RCC cells. Furthermore, the generation of reactive oxygen species and inhibition of the lncRNA THOR played important roles in the antitumour effects of CK in RCC cells. The present data revealed that CK was a potent antitumour agent against RCC.

DOI: https://doi.org/10.3892/or.2021.7989

J Inflamm (Lond). 2021 Mar 04. 18(1): 12

LncRNA TUG1 regulates the development of ischemia-reperfusion mediated acute kidney injury through miR-494-3p/E-cadherin axis.

Li Chen, Jun-Ying Xu, Hong-Bao Tan.

BACKGROUND: Acute kidney injury (AKI) results from renal dysfunction caused by various causes, resulting in high mortality. The underlying mechanisms of ischemia-reperfusion (I/R) induced AKI is very complicated and needed for further research. Here, we sought to found out the functions of lncRNA TUG1 in I/R-induced AKI.
METHODS: In vivo model was constructed by I/R-induced mice and in vitro model was constructed by hypoxia/reoxygenation (H/R)-induced HK-2 cell. Kidney tissue damage was evaluated through H&E staining in mice. Cell flow cytometry was used to detect the degree of apoptosis. TUG1, miR-494-3p and E-cadherin were determined both by RT-PCR and western blot. Dual luciferase assay was employed to validate the relationships between TUG1, miR-494-3p and E-cadherin. Inflammatory factors including IL-1β, TNFɑ and IL-6 were evaluated by ELISA.
RESULTS: lncRNA TUG1 was decreased while miR-494-3p was elevated in vivo and in vitro. Overexpression of TUG1 or transfection with miR-494-3p inhibitor significantly alleviated cell apoptosis. MiR-494-3p directly targeted E-cadherin and TUG1 suppressed cell apoptosis via serving as a miR-494-3p sponge to disinhibit E-cadherin.
CONCLUSION: lncRNA TUG1 alleviated I/R-induced AKI through targeting miR-494-3p/E-cadherin.

Keywords: Acute kidney injury; E-cadherin; lncRNA TUG1; miR-494-3p

DOI: https://doi.org/10.1186/s12950-021-00278-4

Kidney Blood Press Res. 2021 Mar 01. 1-11

Long Noncoding RNA PRNCR1 Reduces Renal Epithelial Cell Apoptosis in Cisplatin-Induced AKI by Regulating miR-182-5p/EZH1.

Jing Li, Xing Fan, Qian Wang, Youlan Gong, Li Guo.

BACKGROUND/AIMS: This study was designed to examine the role of long noncoding RNA PRNCR1 in cisplatin-induced acute kidney injury (AKI) in vitro and in vivo.
METHODS: The expression levels of PRNCR1 and miR-182-5p in cisplatin-induced AKI mice were examined. HK-2 cells were treated with cisplatin to induce cell damage. Then, the effects of PRNCR1 and miR-182-5p on cisplatin-stimulated HK-2 cell viability and apoptosis were detected by the CCK-8 and annexin V-FITC/PI method. Target genes of PRNCR1 and miR-182-5p were analyzed by bioinformatics analysis and luciferase.
RESULTS: The expression level of PRNCR1 was significantly reduced in cisplatin-induced AKI mice. In addition, overexpression of PRNCR1 attenuated the damage of cisplatin to HK-2. The expression level of miR-182-5p was significantly raised in cisplatin-induced AKI mice. MiR-182-5p was negatively regulated by PRNCR1 and leaded to an upregulation of EZH1 expression. Overexpression of PRNCR1 attenuated cisplatin-induced apoptosis by downregulating the miR-182-5p/EZH1 axis.
CONCLUSION: LncPRNCR1 reduced the apoptosis of renal epithelial cells induced by cisplatin by modulating miR-182-5p/EZH1.

Keywords: Acute kidney injury; Apoptosis; EZH1; LncPRNCR1; Proliferation; miR-182-5p

DOI: https://doi.org/10.1159/000510157

Cancer Med. 2021 Mar 02.

Construction and validation of an autophagy-related long noncoding RNA signature for prognosis prediction in kidney renal clear cell carcinoma patients.

JunJie Yu, WeiPu Mao, Bin Xu, Ming Chen.

PURPOSE: The purpose of this study was to identify autophagy-associated long noncoding RNAs (ARlncRNAs) using the kidney renal clear cell carcinoma (KIRC) patient data from The Cancer Genome Atlas (TCGA) database and to construct a prognostic risk-related ARlncRNAs signature to accurately predict the prognosis of KIRC patients.
METHODS: The KIRC patient data were originated from TCGA database and were classified into a training set and testing set. Seven prognostic risk-related ARlncRNAs, identified using univariate, lasso, and multivariate Cox regression analysis, were used to construct prognostic risk-related signatures. Kaplan-Meier curves and receiver operating characteristic (ROC) curves as well as independent prognostic factor analysis and correlation analysis with clinical characteristics were utilized to evaluate and verify the specificity and sensitivity of the signature in training set and testing set, respectively. Two nomograms were established to predict the probable 1-, 3-, and 5-year survival of the KIRC patients. In addition, the lncRNA-mRNA co-expression network was constructed and Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to identify biological functions of ARlncRNAs.
RESULTS: We constructed and verified a prognostic risk-related ARlncRNAs signature in training set and testing set, respectively. We found the survival time of KIRC patients with low-risk scores was significantly better than those with high-risk scores in training set and testing set. ROC curves suggested that the area under the ROC (AUC) value for prognostic risk score signature was 0.81 in training set and 0.705 in testing set. And AUC values corresponding to 1-, 3-, and 5 years of OS were 0.809, 0.753, and 0.794 in training set and 0.698, 0.682, and 0.754 in testing set, respectively. We established the two nomograms that confirmed high C-index and accomplished good prediction accuracy.
CONCLUSIONS: We constructed a prognostic risk-related ARlncRNAs signature that could accurately predict the prognosis of KIRC patients.

Keywords: The Cancer Genome Atlas; autophagy; kidney renal clear cell carcinoma; long noncoding RNA; prognostic signature

DOI: https://doi.org/10.1002/cam4.3820

Aging (Albany NY). 2021 Feb 26. 13

Exosome-derived long non-coding RNA ZFAS1 controls cardiac fibrosis in chronic kidney disease.

Yunfei Wang, Xufen Cao, Liqiu Yan, Ye Zheng, Jing Yu, Fuyun Sun, Zheng Lian, Lina Sun.

The incidence of chronic kidney disease (CKD) complicated with cardiovascular disease (CVD) is increasing day by day. CVD complication is a significant risk factor for the progression and poor prognosis of CKD. However, in terms of clinical diagnosis, treatment, and pathophysiological mechanism, there are still many things that are not clear about CKD combined with CVD. In this article, we observed the abnormal expression of long non-coding RNA ZFAS1 (lncRNA ZFAS1) in the heart and renal tissues of CKD mice, which may a target for nephropathy with CVD. We observed that exosomes containing lncRNA ZFAS1 induced fibrosis in the heart via the wnt4/β-catenin signal pathway. Luciferase assay reported that lncRNA ZFAS1 could bind with microRNA-4711-5p (miR-4711-5p), and wnt4 was a target of miR-4711-5p. In conclusion, lncRNA ZFAS1 from HCM could promote cardiac fibrosis through WNT/β-catenin signal via exosome pathways, which provided an underlying mechanism in the cardiac fibrosis from CKD.

Keywords: cardiac fibrosis; cardiovascular disease; chronic kidney disease; exosome; lncRNA

DOI: https://doi.org/10.18632/aging.202599