bims-lorfki 2021-10-10 papers

Issue of 2021‒10‒10
four papers selected by
Nikita Dewani
Max Delbrück Centre for Molecular Medicine

Front Med (Lausanne). 2021 ;8 714958

Circular RNAs as Novel Diagnostic Biomarkers and Therapeutic Targets in Kidney Disease.

Jianwen Yu, Danli Xie, Naya Huang, Qin Zhou.

Circular RNAs (circRNAs) are a novel type of non-coding RNAs that have aroused growing attention in this decade. They are widely expressed in eukaryotes and generally have high stability owing to their special closed-loop structure. Many circRNAs are abundant, evolutionarily conserved, and exhibit cell-type-specific and tissue-specific expression patterns. Mounting evidence suggests that circRNAs have regulatory potency for gene expression by acting as microRNA sponges, interacting with proteins, regulating transcription, or directly undergoing translation. Dysregulated expression of circRNAs were found in many pathological conditions and contribute to the pathogenesis and progression of various disorders, including renal diseases. Recent studies have revealed that circRNAs may serve as novel reliable biomarkers for the diagnosis and prognosis prediction of multiple kidney diseases, such as renal cell carcinoma (RCC), acute kidney injury (AKI), diabetic kidney disease (DKD), and other glomerular diseases. Furthermore, circRNAs expressed by intrinsic kidney cells are shown to play a substantial role in kidney injury, mostly reported in DKD and RCC. Herein, we review the biogenesis and biological functions of circRNAs, and summarize their roles as promising biomarkers and therapeutic targets in common kidney diseases.

Keywords: biogenesis; biological functions; biomarkers; circular RNAs; kidney diseases; therapeutic targets

DOI: https://doi.org/10.3389/fmed.2021.714958

Genes Genomics. 2021 Oct 08.

Long non-coding RNA TTC28-AS1 attenuates high glucose-induced damage in HK-2 cells depending on the regulation of miR-320a/CD2AP axis.

Ji Zhang, Juan Ding, Ming Yu, Fang Li, Xue Zhou, Hongxia Shuai.

BACKGROUND: Diabetic nephropathy (DN) is the leading cause of end-stage renal disease (ESRD) worldwide. Emerging evidence suggests that long non-coding RNAs (lncRNAs) play crucial roles in DN pathogenesis.OBJECTIVE: The purpose of the present study was to explore the role and mechanism of lncRNA tetratricopeptide repeat domain 2B antisense RNA 1 (TTC28-AS1) in DN.
METHODS: Cell viability and apoptosis were assessed by the Cell Counting-8 Kit (CCK-8) assay and flow cytometry, respectively. The levels of TTC28-AS1, miR-320a and CD2-associated protein (CD2AP) were determined by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. The levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and IL-8 were gauged by enzyme-linked immunosorbent assay (ELISA). Targeted relationship between miR-320a and TTC28-AS1 or CD2AP was evaluated by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays.
RESULTS: Our data indicated that high glucose (HG) induced HK-2 cell damage by the repression of cell viability and autophagy and the enhancement of cell apoptosis, fibrosis and pro-inflammatory cytokines production. TTC28-AS1 was down-regulated and miR-320a was up-regulated in HG-induced HK-2 cells. TTC28-AS1 overexpression or miR-320a knockdown alleviated HG-induced damage in HK-2 cells. MiR-320 was a molecular mediator of TTC28-AS1 in regulating HG-induced HK-2 cell damage. Moreover, TTC28-AS1 functioned as a post-transcriptional regulator of CD2AP expression by miR-320a. MiR-320a knockdown relieved HG-induced damage in HK-2 cells by up-regulating CD2AP.
CONCLUSIONS: Our findings suggest that TTC28-AS1 attenuates HG-induced damage in HK-2 cells at least partially by targeting the miR-320a/CD2AP axis, highlighting its role as a promising therapeutic approach for DN treatment.

Keywords: CD2AP; Cell damage; DN; TTC28-AS1; miR-320a

DOI: https://doi.org/10.1007/s13258-021-01167-z

Kidney Blood Press Res. 2021 Oct 06. 1-11

Elevation of LncRNA ENST00000453774.1 Prevents Renal Fibrosis by Upregulating FBN1, IGF1R, and KLF7.

Xiangning Yuan, Wen-Bin Tang, Ling Peng, Yusa Chen, Shumei Tang, Huipeng Ge, Xiufen Wang, Xiangcheng Xiao.

INTRODUCTION: Transforming growth factor-β (TGF-β), a common outcome of various progressive chronic kidney diseases, can regulate and induce fibrosis.OBJECTIVE: The study aimed to identify downstream targets of lncRNA ENST00000453774.1 (lnc453774.1) and outline their functions on the development of renal fibrosis.
METHODS: HK-2 cells were induced with 5 ng/mL TGF-β1 for 24 h to construct a renal fibrosis cell model. Differentially expressed genes (DEGs) targeted by lnc453774.1 in TGF-β1-induced renal fibrosis were identified using RNA sequencing. The dataset GSE23338 was employed to identify DEGs in 48-h TGF-β1-stimulated human kidney epithelial cells, and these DEGs were intersected with genes in the key module using weighted gene co-expression network analysis to generate key genes associated with renal fibrosis. MicroRNAs (miRs) that had targeting relationship with keys genes and lnc453774.1 were predicted by using Miranda software, and important genes were intersected with key genes that had targeting relationship with these miRs. Key target genes by lnc453774.1 were identified in a protein-protein interaction network among lnc453774.1, important genes, and reported genes related to autophagy, oxidative stress, and cell adhesion.
RESULTS: Key genes in the key module (turquoise) were intersected with DEGs in the dataset GSE23338 and yielded 20 key genes regulated by lnc453774.1 involved in renal fibrosis. Fourteen miRs had targeting relationship with lnc453774.1 and key genes, and 8 important genes targeted by these 14 miRs were identified. Fibrillin-1 (FBN1), insulin-like growth factor 1 receptor (IGF1R), and Kruppel-like factor 7 (KLF7) were identified to be involved in autophagy, oxidative stress, and cell adhesion and were elevated in the lnc453774.1-overexpressing TGF-β1-induced cells.
CONCLUSION: These results show FBN1, IGF1R, and KLF7 serve as downstream targets of lnc453774.1, and that lnc453774.1 may protect against renal fibrosis through competing endogenous miRs which target FBN1, IGF1R, and KLF7 mRNAs.

Keywords: Long noncoding RNA ENST00000453774.1; RNA sequencing; Renal fibrosis; Transforming growth factor-β1; Weighted gene correlation network analysis

DOI: https://doi.org/10.1159/000515624

Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2021 Oct 10. 38(10): 1017-1020

[Influence of long non-coding RNA Gm15645 on the podocyte injury in diabetic nephropathy].

Huan Wang, Guanqiao You, Liqin Guo, Ke Xu, Yansheng Feng.

OBJECTIVE: To explore the influence of long non-coding (lnc) RNA Gm15645 on the podocyte injury in mice with diabetic nephropathy.METHODS: Male db/db mice (with Type 2 diabetes) with a genetic background of C57BLKs/J and db/m mice (healthy) born in littermates were randomly divided into three groups. db/db group was injected with lncRNAGm15645 shRNA lentivirus with a podocyte-specific marker NPHS2; db/db blank group was injected with saline, and db/db control group was injected withnon-sense lentivirus. The results of PAS staining, pathological changes of renal tissue, relative expression of GSK-3beta, and podocin expression were compared.
RESULTS: lncRNAGm15 645 was overexpressed and podocin was down-regulated in the lentivirus overexpressed group. Mesangial cell proliferation, mesangial matrix hyperplasia, thickened basement membrane, widely fused foot process, and podocyte injury were observed by PAS staining. The expression of Gm15645 in the db/db group was significantly lower than that of the db/db blank group and db/db control group (P< 0.05), while the expression of podocin was higher (P< 0.05). Gm15645 was co-stained with podocin in renal tissue, and the target gene was GSK-3beta.
CONCLUSION: lncRNAGm15645 may provide an early biomarker for the occurrence of podocyte injury in diabetic nephropathy. The mechanism may be related to the feedback regulation of GSK-3beta gene.

DOI: https://doi.org/10.3760/cma.j.cn511374-20200903-00650