bims-lorfki 2021-02-28 papers

Issue of 2021‒02‒28
five papers selected by
Nikita Dewani
Max Delbrück Centre for Molecular Medicine

Eur Rev Med Pharmacol Sci. 2021 Feb;pii: 24833. [Epub ahead of print]25(3): 1291-1301

LncRNA DNAJC3-AS1 functions as oncogene in renal cell carcinoma via regulation of the miR-27a-3p/PRDM14 axis.

X-Y Na, X-Q Hu, Y Zhao, C-H Hu, X-S Shang.

OBJECTIVE: Renal cell carcinoma (RCC) is one of the most common urological malignancies worldwide. Although great advances have been made in the diagnosis and management of RCC, its prognosis remains unsatisfactory. Long noncoding RNAs (lncRNAs) have been found to be essential factors in the initiation and development of cancer. The current study aimed to measure the expression and functions of lncRNA DNAJC3-AS1 in the progression of clear cell RCC (ccRCC).PATIENTS AND METHODS: The expression of lncRNA DNAJC3-AS1 was detected in 30 pairs of ccRCC tissues and in cell lines by RT-PCR, and its prognostic association with ccRCC was evaluated by the Kaplan-Meier method. The proliferation, migration, invasion and apoptosis of ccRCC cells were measured after silencing DNAJC3-AS1. The interaction between DNAJC3-AS1, miR-27a-3p and PRDM14 was identified by Dual-Luciferase reporter assay. The protein levels were measured by Western blotting.
RESULTS: The expression of DNAJC3-AS1 was upregulated in ccRCC tissues and cell lines compared to their normal counterparts. In vitro, silencing DNAJC3-AS1 reduced the proliferation, migration and invasion of ccRCC cells. Downregulation of DNAJC3-AS1 also led to the apoptosis of ccRCC cells. Moreover, we also found that DNAJC3-AS1 acted as a sponge of miR-27a-3p and identified PRDM14 as a target of miR-27a-3p.
CONCLUSIONS: LncRNA DNAJC3-AS1 acts as an oncogene and plays an essential role in the tumorigenesis of ccRCC, possibly via the regulation of the miR-27a-3p/PRDM14 axis.

DOI: https://doi.org/10.26355/eurrev_202102_24833

PeerJ. 2021 ;9 e10668

An integrated analysis of lncRNA and mRNA expression profiles in the kidneys of mice with lupus nephritis.

Juan Wang, Xiongfei Wu, Yafang Tu, Jianzhong Dang, Zhitao Cai, Wenjing Liao, Weili Quan, Yaxun Wei.

Long noncoding RNAs (lncRNAs) are persistently expressed and have been described as potential biomarkers and therapeutic targets in various diseases. However, there is limited information regarding lncRNA expression in the tissue of kidney exhibiting lupus nephritis (LN)a serious complication of systemic lupus erythematosus (SLE). In this study, RNA sequencing (RNA-seq) was performed to characterize the lncRNA and mRNA expression in kidney tissues from LN (MRL/lpr) and control mice. We identified 12,979 novel lncRNAs in mouse. The expression profiles of both mRNAs and lncRNAs were differed significantly between LN and control mice. In particular, there were more upregulated lncRNAs and mRNAs than downregulated ones in the kidney tissues of LN mice. However, GO analysis showed that more downregulated genes were enriched in immune and inflammatory response-associated pathways. KEGG analysis showed that both downregulated and upregulated genes were enriched in a number of pathways, including the SLE pathway, and approximately half of these SLE-associated genes encoded inflammatory factors. Moreover, we observed that 2,181 DElncRNAs may have targeted and regulated the expression of 778 mRNAs in LN kidney tissues. The results of this study showed that 11 DElncRNAs targeted and were co-expressed with six immune and SLE-associated genes. qPCR analysis confirmed that lncRNA Gm20513 positively regulated the expression of the SLE-associated gene H2-Aa. In conclusion, the results of our study demonstrates that lncRNAs influence the progression of LN and provide some cues for further study of lncRNAs in LN. These results regarding the lncRNA-mRNAregulatory network may have important value in LN diagnosis and therapy.

Keywords: Differentially expressed genes; Immune response; Lupus nephritis; RNA sequencing; lncRNAs

DOI: https://doi.org/10.7717/peerj.10668

Expert Rev Mol Diagn. 2021 Feb 20. 1-13

Identification of the candidate lncRNA biomarkers for acute kidney injury: a systematic review and meta-analysis.

Tiantian Ma, Hongshuai Jia, Peili Ji, Yangzhige He, Limeng Chen.

Background: This meta-analysis aims to summarize the studies of lncRNAs dysregulation in individual acute kidney injury (AKI) and identify the potential lncRNA biomarkers of AKI. Research design and methods: We systematically searched four databases to identify the lncRNA expression studies of AKI in animal models and patients. The lncRNAs expression data were extracted from 38 included studies, and lncRNA vote-counting strategy was applied to identify significant lncRNA biomarkers. The predicted targets of lncRNA biomarkers were obtained by searching Co-LncRNA, RBPmap, and LncBase v.2. Further, GO enrichment analysis and KEGG pathway analysis were performed. Results: We recognized a significant lncRNA signature of 21 up-regulated and 11 down-regulated lncRNAs, among which TapSAKI, XIST, MALAT1, CASC2, and HOXA-AS2 were dysregulated both in AKI rodent models and patients. About 28.0% of these lncRNAs mainly exist in the nucleus, which was also the most enriched GO cellular components term. The most relevant GO terms in biological process and molecular function associated with these lncRNAs were splicing, processing, and binding of mRNA. Conclusions: The present meta-analysis identified 31 significant dysregulated lncRNAs from 38 studies. TapSAKI, XIST, MALAT1, CASC2, and HOXA-AS2 were considered as the potential predictive biomarkers and therapeutic targets of AKI.

Keywords: Acute kidney injury; biomarkers; diagnosis; lncRNA; systematic review

DOI: https://doi.org/10.1080/14737159.2021.1873131

Yonsei Med J. 2021 Mar;62(3): 262-273

Long Non-Coding RNA RMRP Contributes to Sepsis-Induced Acute Kidney Injury.

Xia Zhang, Zhongwei Huang, Yan Wang, Ting Wang, Jingjing Li, Peipei Xi.

PURPOSE: This study aimed to explore the role of the long non-coding RNA (lncRNA) RNA component of mitochondrial RNAase P (RMRP) in sepsis-induced acute kidney injury (AKI).MATERIALS AND METHODS: Venous blood was collected from septic patients and healthy people. C57BL/6 mice who underwent cecal ligation and puncture (CLP) were used as in vivo models of septic AKI. Lipopolysaccharide (LPS)-induced HK-2 cells were employed as in vitro models of AKI. Flow cytometry analysis was conducted to detect cell apoptosis. Enzyme-linked immunosorbent assay and Western blot assays were used to detect levels of pro-inflammatory cytokines.
RESULTS: RMRP was upregulated in sera from patients with AKI and in LPS-induced cells. Knockdown of RMRP inhibited cell apoptosis and reduced production of inflammatory factors in LPS-induced cells, as well as alleviated AKI in CLP mice. RMRP facilitated inflammation by activating NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome. We found that microRNA 206 (miR-206) binds with and is negatively regulated by RMRP: miR-206 directly targets the 3' untranslated region of DEAD-box helicase 5 (DDX5) and negatively regulates DDX5 expression. By binding with miR-206, RMRP upregulated DDX5 expression. Rescue assays revealed that overexpression of DDX5 counteracted the effect of RMRP inhibition on cell apoptosis and inflammatory response in LPS-induced cells.
CONCLUSION: The lncRNA RMRP contributes to sepsis-induced AKI through upregulation of DDX5 in a miR-206 dependent manner and through activation of NLRP3 inflammasome. This novel discovery may provide a potential strategy for treating AKI.

Keywords: DDX5; NLRP3 inflammasome; RMRP; miR-206; sepsis-induced AKI

DOI: https://doi.org/10.3349/ymj.2021.62.3.262