Dysregulation of tRNA-derived small RNAs and their potential roles in lupus nephritis

Liang, Yan; Zhang, Ji; Qiu, Wenxian; Chen, Bin; Zhou, Ying; Chen, Xiaoqian; Shentu, Yangping; Zhang, Huidi; Bai, Yongheng; Chen, Chaosheng

doi:10.1177/09612033211061482

Cited by 6 publications

(4 citation statements)

References 29 publications

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“…32,33 Yan Liang et al found that tRNA-derived small RNAs might contribute to the pathogenesis of lupus nephritis via the PI3K/AKT pathway. 34 Here, we discovered that downregulating miR-99a-3p expression in BALL-1 cells greatly enhanced the PI3K/AKT pathway activation, whereas downregulating NCAPG expression could inhibit the phosphorylation of PI3K and AKT. Also, we found that LY294002 partially blocked the effects of the miR-99a-3p antagonist on BALL-1 cell proliferation, apoptosis, and the cell cycle transition.…”

Section: Discussionmentioning

confidence: 85%

Reduced miR-99a-3p levels in systemic lupus erythematosus may promote B cell proliferation via NCAPG and the PI3K/AKT signaling pathway

Zhu,

Zhou,

Yang

et al. 2024

Lupus

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Background Systemic lupus erythematosus is an immunologically dysregulated disease characterized by the presence of multiple autoantibodies. In SLE, B lymphocytes contribute to the dysregulated production of autoantibodies and cytokines. Recently, we discovered that miR-99a-3p binds to both EIF4EBP1 and NCAPG mRNA and that lowering miR-99a-3p can promote B cell autophagy in SLE by increasing EIF4EBP1 expression. However, the functions of miR-99a-3p and NCAPG in SLE have not been extensively investigated. Objective This work aims to evaluate the levels of miR-99a-3p and NCAPG expression in SLE B cells and to determine whether the aberrant expression of miR-99a-3p and NCAPG contributes to the pathological mechanisms in SLE. Methods B lymphocytes were obtained through immunomagnetic negative selection. Using RT-qPCR, miR-99a-3p and NCAPG mRNA expressions in B lymphocytes and in the BALL-1 cell line were measured. To determine the relative abundance of NCAPG, PI3K, p-PI3K, AKT, and p-AKT, we normalize them to the level of β-actin using Western blotting. Evaluation of miR-99a-3p and NCAPG’s impact on cell proliferation was done utilizing CCK-8 assay. Using flow cytometry, the cell cycle and apoptosis were both measured. Results Comparing SLE B cells to healthy controls, miR-99a-3p expression was significantly downregulated. Additionally, it was observed that SLE B cells had significantly higher NCAPG mRNA expression. Blocking miR-99a-3p expression in BALL-1 cells with an antagomir elevated NCAPG expression, facilitated PI3K/AKT pathway activation, improved cell proliferation, raised the fraction of S-phase cells, and prevented cell apoptosis. The opposite effects of upregulated miR-99a-3p levels on BALL-1 cells were observed by using an agomir. Furthermore, the effect of decreased miR-99a-3p expression on cell proliferation was partially mediated by elevating NCAPG levels and activating the PI3K/AKT pathway. Conclusion Our research indicates that lower miR-99a-3p expression in SLE B cells appears to boost B cell number via the NCAPG and PI3K/AKT pathways.

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Section: Discussionmentioning

confidence: 85%

Reduced miR-99a-3p levels in systemic lupus erythematosus may promote B cell proliferation via NCAPG and the PI3K/AKT signaling pathway

Zhu,

Zhou,

Yang

et al. 2024

Lupus

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“…A total of 160 tsRNAs were identified by high-throughput sequencing in LN renal tissue, of which 79 were upregulated and 81 were downregulated. Bioinformatics analysis predicts that tsRNAs may play a role in the pathogenesis of LN through cell adhesion molecules as well as the B-cell receptor, PI3K-AKT, and MAPK signaling pathways ( 111 ). A total of 101 tRNAs and 355 tsRNAs were differentially expressed in PBMCs of SLE patients.…”

Section: Candidate Rnas As Sle Biomarkersmentioning

confidence: 99%

Progress in the application of body fluid and tissue level mRNAs-non-coding RNAs for the early diagnosis and prognostic evaluation of systemic lupus erythematosus

et al. 2022

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The diagnosis and differential classification of systemic lupus erythematosus (SLE) is difficult, especially in patients with early-onset SLE who are susceptible to systemic multi-organ damage and serious complications and have difficulties in individualized treatment. At present, diagnosis is based mainly on clinical manifestations and the detection of serological antinuclear antibodies. The pathogenesis of SLE involves multiple factors, is clinically heterogeneous, and lacks specific biomarkers. Therefore, it is necessary to identify new biomarkers for the diagnosis and subtype classification of SLE. Non-coding RNAs (ncRNAs) are composed of microRNAs, long non-coding RNAs, small nucleolar RNAs, circular RNAs, and transfer RNAs. They play an important role in the occurrence and development of diseases and are used widely in the early diagnosis and prognosis of autoimmune diseases. In this review, we focus on the research progress in the diagnosis and prognostic assessment of SLE using humoral to tissue level ncRNAs.

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“…Mounting evidence has indicated that the aberrated expression of tsRNAs are deeply implicated in cancer, parasitic disease (12)(13)(14)(15)(16). Recently, a few studies including our previous research pay attention to the relationship between SLE and tsRNA (14,(17)(18)(19). However, the diagnostic values and biological functions of tsRNAs in urinary exosome, especially for LN, are still ambiguous and intriguing.…”

Section: Introductionmentioning

confidence: 99%

Urinary exosome tsRNAs as novel markers for diagnosis and prediction of lupus nephritis

et al. 2023

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ObjectiveLupus nephritis (LN) is one of the most severe organ manifestations of systemic lupus erythematosus (SLE). Early identification of renal disease in SLE is important. Renal biopsy is currently recognized as the gold standard for diagnosing LN, however, it is invasive and inconvenient for dynamic monitoring. Urine has been considered more promising and valuable than blood in identifying inflamed kidney tissue. Here, we determine whether the signatures of tRNA-derived small noncoding RNA (tsRNA) in urinary exosomes can serve as novel biomarkers for the diagnosis of LN.MethodstsRNA sequencing was performed in exosome extracted from pooled urine of 20 LN patients and 20 SLE without LN, and the top 10 upregulated tsRNAs were screened as candidate markers of LN. The candidate urinary exosomal tsRNAs were primarily elected by TaqMan probe-based quantitative reverse transcription-PCR (RT-PCR) in 40 samples (20 LN and 20 SLE without LN) in the training phase. In the validation phase, selected tsRNAs from the training phase were further confirmed in a larger cohort (54 LN patients and 39 SLE without LN). Receiver operating characteristic curve (ROC) analysis was conducted to evaluate the diagnostic efficacy.ResultsUpregulated levels of tRF3-Ile-AAT-1 and tiRNA5-Lys-CTT-1 in the urinary exosomes were observed in LN compared with SLE without LN (P < 0.0001 and P < 0.001) and healthy controls (P < 0.01 and P < 0.01), with the area under the curve (AUC) of 0.777 (95% CI: 0.681-0.874, sensitivity 79.63%, specificity 66.69%) and 0.715 (95% CI: 0.610-0.820, sensitivity 66.96%, specificity 76.92%) for discriminating LN from SLE without LN patients. SLE patients with mild activity and moderate to severe activity had higher levels of urinary exosome derived tRF3-Ile AAT-1 (P = 0.035 and P < 0.001) and tiRNA5-Lys-CTT-1 (P = 0.021 and P < 0.001) compared with patients with no activity. Moreover, bioinformatics analysis revealed that both of the tsRNAs regulate the immune process by modulating metabolism and signal pathway.ConclusionIn this study, we demonstrated that urinary exosome tsRNAs can be served as noninvasive biomarkers for the efficient diagnosis and prediction of nephritis in SLE.

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Dysregulation of tRNA-derived small RNAs and their potential roles in lupus nephritis

Cited by 6 publications

References 29 publications

Reduced miR-99a-3p levels in systemic lupus erythematosus may promote B cell proliferation via NCAPG and the PI3K/AKT signaling pathway

Reduced miR-99a-3p levels in systemic lupus erythematosus may promote B cell proliferation via NCAPG and the PI3K/AKT signaling pathway

Progress in the application of body fluid and tissue level mRNAs-non-coding RNAs for the early diagnosis and prognostic evaluation of systemic lupus erythematosus

Urinary exosome tsRNAs as novel markers for diagnosis and prediction of lupus nephritis

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