bims-lorfki Biomed News
on Long non-coding RNA functions in the kidney
Issue of 2020–08–30
two papers selected by
Nikita Dewani, Max Delbrück Centre for Molecular Medicine
  1. Long non-coding RNA Dlx6os1 serves as a potential treatment target for diabetic nephropathy via regulation of apoptosis and inflammation.
  2. Circulating Expression Level of LncRNA Malat1 in Diabetic Kidney Disease Patients and Its Clinical Significance.
  1. Exp Ther Med. 2020 Oct;20(4): 3791-3797
    Long non-coding RNA Dlx6os1 serves as a potential treatment target for diabetic nephropathy via regulation of apoptosis and inflammation.
    Li Cheng, Jie Cheng, Wenfang Peng, Xiaohong Jiang, Shan Huang.
      The present study investigated the effect of long non-coding RNA (lncRNA) Dlx6os1 silencing on cell proliferation, apoptosis and fibrosis, and further explored its influence on the mRNA expression profile in mouse mesangial cells (MMCs) of a diabetic nephropathy (DN) cellular model. A DN cellular model was constructed in SV40 MES13 MMCs under high glucose conditions (30 mmol/l glucose culture). lncRNA Dlx6os1 short hairpin (sh)RNA plasmids and negative control (NC) shRNA plasmids were transfected into the MMCs of the DN cellular model as the sh-lncRNA group and sh-NC group respectively. The mRNA expression profile was determined in the sh-lncRNA and sh-NC groups. Compared with the sh-NC group, the cell proliferation, mRNA and protein expression levels of proliferative markers (cyclin D1 and proliferating cell nuclear antigen) as well as fibrosis markers (fibronectin and collagen I) were suppressed, whereas cell apoptosis was promoted in the sh-lncRNA group. The mRNA expression profile identified 423 upregulated mRNAs and 438 downregulated mRNAs in the sh-lncRNA group compared with the sh-NC group. Additionally, Gene Ontology/Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed that the differentially expressed mRNAs were enriched in apoptosis and inflammation-related pathways. Further gene-set enrichment analysis of apoptosis and inflammation revealed that lncRNA Dlx6os1 inhibition promoted apoptosis and suppressed inflammation in MMCs of the DN cellular model. In conclusion, lncRNA Dlx6os1 may serve as a potential treatment target for DN via regulation of multiple apoptosis- and inflammation-related pathways.
    Keywords:  apoptosis; diabetic nephropathy; inflammation; long non-coding RNA Dlx6os1; mRNA
    DOI:  https://doi.org/10.3892/etm.2020.9112
  2. J Diabetes Res. 2020 ;2020 4729019
    Circulating Expression Level of LncRNA Malat1 in Diabetic Kidney Disease Patients and Its Clinical Significance.
    Lian-Ji Zhou, Da-Wei Yang, Li-Na Ou, Xing-Rong Guo, Biao-Liang Wu.
       Background: Long noncoding RNA MALAT1 is closely related to diabetes and kidney diseases and is expected to be a new target for the diagnosis and treatment of diabetic nephropathy.
    Objective: This study aimed to explore the circulating expression level and significance of lncRNA Malat1 in patients with type 2 diabetes mellitus (T2DM) and diabetic kidney disease (DKD).
    Methods: Quantitative real-time PCR (qPCR) was conducted to assess the expression of lncRNA Malat1 in 20 T2DM patients, 27 DKD patients, and 14 healthy controls, and then, the clinical significance was analyzed.
    Results: LncRNA MALAT1 expression in peripheral blood mononuclear cells (PBMC) was significantly upregulated in T2DM and DKD groups when compared to control. Pearson's correlation analysis showed correlation of lncRNA MALAT1 levels with ACR, urine β2-microglobulin (β2-MG), urine α1-microglobulin (α1-MG), creatinine (Cr), and glycosylated hemoglobin (HbA1c), while negative with superoxide dismutase (SOD) (r = -0.388, P < 0.05). Binary regression analysis showed that ACR, creatinine, α1-MG, and LncRNA Malat1 were the risk factors for diabetic nephropathy with OR value of 1.166, 1.031, 1.031, and 2.019 (P < 0.05). The area under ROC curve (AUC) of DKD identified by the above indicators was 0.914, 0.643, 0.807, and 0.797, respectively. The AUC of Joint prediction probability of DKD recognition was 0.914, and the sensitivity and specificity of DKD diagnosis were 1.0 and 0.806, respectively. (Take ≥0.251 as the diagnostic cutoff point).
    Conclusion: LncRNA Malat1 is highly expressed in DKD patients, and the combined detection of ACR, creatinine, α1-MG, and LncRNA Malat1 with diabetes mellitus may be the best way to diagnose diabetic nephropathy.
    DOI:  https://doi.org/10.1155/2020/4729019
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