bims-lorfki Biomed News
on Long non-coding RNA functions in the kidney
Issue of 2021–03–28
two papers selected by
Nikita Dewani, Max Delbrück Centre for Molecular Medicine
  1. Novel biomarkers for post-contrast acute kidney injury identified from long non-coding RNA expression profiles.
  2. Lnc-ing pluripotency maintenance and early differentiation in human pluripotent stem cells.
  1. Int J Biol Sci. 2021 ;17(3): 882-896
    Novel biomarkers for post-contrast acute kidney injury identified from long non-coding RNA expression profiles.
    Guanzhong Chen, Bowen Liu, Shiqun Chen, Huanqiang Li, Jin Liu, Ziling Mai, Enzhao Chen, Chunyun Zhou, Guoli Sun, Zhaodong Guo, Li Lei, Shanyi Huang, Liyao Zhang, Min Li, Ning Tan, Hong Li, Yulin Liao, Jia Liu, Jiyan Chen, Yong Liu.
      Background: Post-contrast acute kidney injury (PC-AKI) is a severe complication of cardiac catheterization. Emerging evidence indicated that long non-coding RNAs (lncRNAs) could serve as biomarkers for various diseases. However, the lncRNA expression profile and potential biomarkers in PC-AKI remain unclear. This study aimed to investigate novel lncRNA biomarkers for the early detection of PC-AKI. Methods: lncRNA profile in the kidney tissues of PC-AKI rats was evaluated through RNA sequencing. Potential lncRNA biomarkers were identified through human-rat homology analysis, kidney and blood filtering in rats and verified in 112 clinical samples. The expression patterns of the candidate lncRNAs were detected in HK-2 cells and rat models to evaluate their potential for early detection. Results: In total, 357 lncRNAs were found to be differentially expressed in PC-AKI. We identified lnc-HILPDA and lnc-PRND were conservative and remarkably upregulated in both kidneys and blood from rats and the blood of PC-AKI patients; these lncRNAs can precisely distinguish PC-AKI patients (area under the curve (AUC) values of 0.885 and 0.875, respectively). The combination of these two lncRNAs exhibited improved accuracy for predicting PC-AKI, with 100% sensitivity and 83.93% specificity. Time-course experiments showed that the significant difference was first noted in the blood of PC-AKI rats at 12 h for lnc-HILPDA and 24 h for lnc-PRND. Conclusion: Our study revealed that lnc-HILPDA and lnc-PRND may serve as the novel biomarkers for early detection and profoundly affect the clinical stratification and strategy guidance of PC-AKI.
    Keywords:  bioinformatics; biomarker; long non-coding RNA; post-contrast acute kidney injury
    DOI:  https://doi.org/10.7150/ijbs.45294
  2. FASEB J. 2021 Apr;35(4): e21438
    Lnc-ing pluripotency maintenance and early differentiation in human pluripotent stem cells.
    Pei Lu, Mao Li, Donghui Zhang, Wei Jiang.
      Pluripotency maintenance and lineage differentiation are two major characteristics of human embryonic and induced pluripotent stem cells. The determination of self-renewal or differentiation is under the exquisite control of the gene regulatory network, which is composed of transcription factors, signaling pathways, metabolic factors, chromatin or histone modifiers, miRNAs, and lncRNAs. Growing evidence has shown that long noncoding RNAs (lncRNAs) play important roles in epigenetic, transcriptional, and posttranscriptional gene regulation during the cell fate determination of pluripotent stem cells. Here, we summarize recent reports of lncRNA functions in pluripotency maintenance/exit and the early germ layer specification of human pluripotent stem cells. We also illustrate four major lncRNA functional mechanisms according to different types of cofactors: chromatin or histone modifiers, transcription factors, canonical and noncanonical RNA-binding proteins, and miRNAs. Further understanding of lncRNA-based regulation will provide more insights into the drivers manipulating cell fate and promote the therapeutic and research potential of human embryonic and induced pluripotent stem cells.
    Keywords:  early differentiation; human embryonic stem cell; induced pluripotent stem cell; lncRNA; pluripotency
    DOI:  https://doi.org/10.1096/fj.202002278R
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