bims-lorfki Biomed News
on Long non-coding RNA functions in the kidney
Issue of 2022–02–27
three papers selected by
Nikita Dewani, Max Delbrück Centre for Molecular Medicine
  1. LncRNA HOTAIR facilitates high glucose-induced mesangial cell proliferation, fibrosis and oxidative stress in diabetic nephropathy via regulating miR-147a/WNT2B axis.
  2. [Role and mechanism of non-coding RNA in the pathogenesis of acute kidney injury].
  3. LncRNA GAS5 rs145204276 Polymorphism Reduces Renal Cell Carcinoma Susceptibility in Southern Chinese Population.
  1. Diabetol Metab Syndr. 2022 Feb 22. 14(1): 33
    LncRNA HOTAIR facilitates high glucose-induced mesangial cell proliferation, fibrosis and oxidative stress in diabetic nephropathy via regulating miR-147a/WNT2B axis.
    Xin Wang, Wei Wang, Weizhong HuangFu, Zhonghua Liu, Feng Zhao.
       BACKGROUND: Long non-coding RNAs (lncRNAs) have been shown to be involved in the regulation of many disease progression. However, the role of lncRNA HOX transcript antisense RNA (HOTAIR) in diabetic nephropathy (DN) remains unclear.
    METHODS: High glucose (HG)-induced human mesangial cells (HMC) was used to construct DN cell models in vitro. HMC proliferation was evaluated by CCK8 assay and EDU staining. Protein levels of proliferation markers, fibrosis markers, and wingless-type family member 2B (WNT2B) were measured using western blot analysis. HMC oxidative stress was assessed by determining the levels of oxygen species and malondialdehyde, as well as superoxide dismutase activity. Relative expression levels of lncRNA HOTAIR, microRNA (miR)-147a, and WNT2B were examined using quantitative real-time PCR. The interaction between miR-147a and lncRNA HOTAIR or WNT2B was confirmed by dual-luciferase reporter assay and RIP assay.
    RESULTS: Our data showed that lncRNA HOTAIR knockdown could inhibit the proliferation, fibrosis, and oxidative stress in HG-induced HMC. LncRNA HOTAIR could serve as a sponge of miR-147a. The inhibition effect of lncRNA HOTAIR silencing on the biological functions of HG-induced HMC could be reversed by miR-147a inhibitor. WNT2B was targeted by miR-147a, and its overexpression also overturned the suppressive effect of miR-147a on the proliferation, fibrosis, and oxidative stress of HG-induced HMC.
    CONCLUSION: In total, our research pointed out that lncRNA HOTAIR could mediate miR-147a/WNT2B axis to promote DN progression.
    Keywords:  Diabetic nephropathy; WNT2B; lncRNA HOTAIR; miR-147a
    DOI:  https://doi.org/10.1186/s13098-022-00802-3
  2. Sheng Li Xue Bao. 2022 Feb 25. 74(1): 39-46
    [Role and mechanism of non-coding RNA in the pathogenesis of acute kidney injury].
    Peng Wang, Miao-Miao Zhou, Jing Nie.
      Acute kidney injury (AKI) is a common clinical syndrome and an independent risk factor of chronic kidney disease and end-stage renal failure. At present, the treatments of AKI are still very limited and the morbidity and mortality of AKI are rising. Non-coding RNAs (ncRNAs), including microRNAs, long non-coding RNAs and circular RNAs (circRNAs), are RNAs that are transcribed from the genome, but not translated into proteins. It has been widely reported that ncRNA is involved in AKI caused by ischemia reperfusion injury (IRI), drugs and sepsis through different molecular biological mechanisms, such as apoptosis and oxidative stress response. Therefore, ncRNAs are expected to become a new target for clinical prevention and treatment of AKI and a new biomarker for early warning of the occurrence and prognosis of AKI. Here, the role and mechanism of ncRNA in AKI and the research progress of ncRNA as biomarkers are reviewed.
  3. J Inflamm Res. 2022 ;15 1147-1158
    LncRNA GAS5 rs145204276 Polymorphism Reduces Renal Cell Carcinoma Susceptibility in Southern Chinese Population.
    Xiaoyao Xiang, Linfa Chen, Jiawen He, Guoda Ma, You Li.
       Objective: Recent studies have demonstrated that the long non-coding RNA (lncRNA) GAS5 is closely associated with the onset and progression of several tumor types, including renal cell carcinoma (RCC). This study sought to evaluate the relationship between two functional GAS5 polymorphisms (rs145204276 and rs55829688) and the risk for RCC in the Han Chinese population.
    Methods: The rs145204276 and rs55829688 polymorphisms in the GAS5 promoter region were genotyped in 624 RCC patients and 655 age/sex-matched healthy participants. The association between these polymorphisms and RCC risk was then evaluated using odds ratios (ORs) and corresponding 95% confidence intervals (CIs). Additionally, quantitative RT-PCR was used to determine whether these polymorphisms were associated with changes in the levels of expression of GAS5 in 58 RCC patients.
    Results: There were significant differences in the GAS5 rs145204276 polymorphism genotype and allele frequencies between the RCC patients and controls (adjusted OR = 0.73, 95% CI = 0.61- 0.87, P = 1.8×10-3). When the study participants were stratified based on age, sex, BMI index, and smoking and drinking history, we found that the rs145204276 del allele was associated with a reduced risk for RCC in nondrinkers (P = 3.3×10-3), nonsmokers (P = 3.3×10-3), females (P = 3.8×10-3), and those who were less than 60 years old (P = 3.3×10-3). There was also a significant association between the rs145204276 del allele and elevated expression of GAS5 in RCC patients (P = 0.030).
    Conclusions: The results of this study revealed an association between the rs145204276 polymorphism in the GAS5 lncRNA and the risk for the development of RCC, thus representing a potentially viable biomarker for identifying individuals at risk of developing this form of cancer.
    Keywords:  case-control; lncRNA GAS5; polymorphism; renal cell carcinoma
    DOI:  https://doi.org/10.2147/JIR.S348628
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