bims-lorfki 2021-08-22 papers

Issue of 2021‒08‒22
four papers selected by
Nikita Dewani
Max Delbrück Centre for Molecular Medicine

Biosci Rep. 2021 Aug 17. pii: BSR20211451. [Epub ahead of print]

Identification of a glycolysis-related lncRNA prognostic signature for clear cell renal cell carcinoma.

BACKGROUND: This study investigated the independent prognostic value of glycolysis-related long noncoding (lnc)RNAs in clear cell renal cell carcinoma (ccRCC).METHODS: A coexpression analysis of glycolysis-related mRNAs-lncRNAs in ccRCC from The Cancer Genome Atlas was carried out. Clinical samples were randomly divided into training and validation sets. Univariate Cox regression and least absolute shrinkage and selection operator regression analyses were performed to establish a glycolysis risk model with prognostic value for ccRCC, which was validated in the training and validation sets and in the whole cohort by Kaplan-Meier, univariate and multivariate Cox regression, and receiver operating characteristic (ROC) curve analyses. Principal component analysis and functional annotation by gene set enrichment analysis (GSEA) were performed to evaluate the risk model.
RESULTS: We identified 297 glycolysis-associated lncRNAs in ccRCC; of these, 7 were found to have prognostic value in ccRCC patients by Kaplan-Meier, univariate and multivariate Cox regression, and ROC curve analyses. The results of the GSEA suggested a close association between the 7-lncRNA signature and glycolysis-related biological processes and pathways.
CONCLUSION: The 7 identified glycolysis-related lncRNAs constitute a lncRNA signature with prognostic value for ccRCC and provide potential therapeutic targets for the treatment of ccRCC patients.

Keywords: clear cell renal cell carcinoma (ccRCC); glycolysis; long noncoding RNAs (lncRNAs); prognosis; risk model

DOI: https://doi.org/10.1042/BSR20211451

J Int Med Res. 2021 Aug;49(8): 3000605211037495

The lncRNA CASC9 alleviates lipopolysaccharide-induced acute kidney injury by regulating the miR-424-5p/TXNIP pathway.

Hai-Peng Fan, Zhi-Xia Zhu, Jia-Jun Xu, Yu-Tang Li, Chun-Wen Guo, Hong Yan.

OBJECTIVE: This study aimed to clarify the mechanism by which the long non-coding RNA cancer susceptibility candidate 9 (CASC9) alleviates sepsis-related acute kidney injury (S-AKI).METHODS: A lipopolysaccharide (LPS)-induced AKI model was established to simulate S-AKI. HK-2 human renal tubular epithelial cells were treated with LPS to establish an in vitro model, and mice were intraperitoneally injected with LPS to generate an in vivo model. Subsequently, the mRNA expression of inflammatory and antioxidant factors was validated by quantitative reverse transcription polymerase chain reaction (RT-qPCR). Reactive oxygen species (ROS) production was assessed using an assay kit. Apoptosis was detected by western blotting and fluorescence-activated cell sorting.
RESULTS: CASC9 was significantly downregulated in the LPS-induced AKI model. CASC9 attenuated cell inflammation and apoptosis and enhanced the antioxidant capacity of cells. Regarding the mechanism, miR-424-5p was identified as the downstream target of CASC9, and the interaction between CASC9 and miR-424-5p promoted thioredoxin-interacting protein (TXNIP) expression.
CONCLUSIONS: CASC9 alleviates LPS-induced AKI in vivo and in vitro, and CASC9 directly targets miR-424-5p and further promotes the expression of TXNIP. We have provided a possible reference strategy for the treatment of S-AKI.

Keywords: Long non-coding RNA; antioxidant; apoptosis; cancer susceptibility candidate 9; inflammation; lipopolysaccharide; miR-424-5p; sepsis-related acute kidney injury; thioredoxin-interacting protein

DOI: https://doi.org/10.1177/03000605211037495

Front Oncol. 2021 ;11 711736

A Novel Prognostic Model Based on Autophagy-Related Long Non-Coding RNAs for Clear Cell Renal Cell Carcinoma.

Xinyuan Li, Haitao Yu, Zongjie Wei, Xin Gou, Simin Liang, Fu Liu.

Background: Renal cell carcinoma (RCC) is one of the most common malignant tumors of the urinary system, of which the clear cell renal cell carcinoma (ccRCC) accounts for the most subtypes. The increasing discoveries of abundant autophagy-related long non-coding RNAs (ARLNRs) lead to a resurgent interest in evaluating their potential on prognosis prediction. Based on a large number of ccRCC gene samples from TCGA and clinics, ARLNRs analysis will provide a novel perspective into this field.Methods: We calculated the autophagy scores of each sample according to the expression levels of autophagy-related genes (ARGs) and screened the survival-related ARLNRs (sARLNRs) of ccRCC patients by Cox regression analysis. The high-risk group and the low-risk group were distinguished by the median score of the autophagy-related risk score (ARRS) model. The functional annotations were detected by gene set enrichment analysis (GSEA) and principal component analysis (PCA). The expression levels of two kinds of sARLNRs in the renal tumor and adjacent normal tissues and cell lines were verified.
Results: There were 146 ARLNRs selected by Pearson analysis. A total of 30 sARLNRs were remarkably correlated with the clinical outcomes of ccRCC patients. Eleven sARLNRs (AC002553.1, AC092611.2, AL360181.2, AP002807.1, AC098484.1, AL513218.1, AC008735.2, MHENCR, AC020907.4, AC011462.4, and AC008870.2) with the highest prognosis value were recruited to establish the ARRS in which the overall survival (OS) in the high-risk group was shorter than that in the low-risk group. ARRS could be treated as an independent prognostic factor and has significant correlations with OS. The distributions of autophagy genes were different between the high-risk group and the low-risk group. In addition, we also found that the expression levels of AC098484.1 in ccRCC cell lines and tumor tissues were lower than those in HK-2 and adjacent normal tissues, but AL513218.1 showed the inverse level. Furthermore, the AC098484.1 expressed decreasingly with the more advanced T-stages, but AL513218.1 gradually increased.
Conclusion: Our study identified and verified some sARLNRs with clinical significances and revealed their potential values on predicting prognoses of ccRCC patients, which may provide a novel perspective for autophagy-related research and clinical decisions.

Keywords: autophagy-related genes; ccRCC; long non-coding RNAs; prognosis; risk model

DOI: https://doi.org/10.3389/fonc.2021.711736

Methods Mol Biol. 2021 ;2372 85-92

Capturing Endogenous Long Noncoding RNAs and Their Binding Proteins Using Chromatin Isolation by RNA Purification.

Jongchan Kim, Li Ma.

Long noncoding RNAs (lncRNAs) exert their functions through binding to other RNA, genomic DNA, or proteins. The identification of proteins that associate with the lncRNA of interest sheds light on the molecular basis of its biological functions. This can be achieved by tagging the lncRNA with chemically modified ribonucleotides, or by using in vitro transcribed lncRNA to retrieve proteins from cell lysates. Alternatively, endogenous lncRNAs can be pulled down from cells or tissues with biotinylated antisense DNA oligonucleotides, which may overcome the potential pitfalls of using tagged lncRNAs, such as artifacts caused by tagging or non-physiological interactions. Here we describe the detailed protocol for chromatin isolation by RNA purification (ChIRP) from mammalian cell lines and mouse tissues, which captures endogenous lncRNAs and enables subsequent identification of their physiologically relevant binding partners.

Keywords: ChIRP; Mass spectrometry; RNA-binding protein; lncRNA

DOI: https://doi.org/10.1007/978-1-0716-1697-0_9