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. 2023 Jul;12(2):220-232.
doi: 10.61186/rbmb.12.2.220.

Circulating miR-21 Overexpression Correlates with PDCD4 and IL-10 in Systemic Lupus Erythematosus (SLE): A Promising Diagnostic and Prognostic Biomarker

Nibras Kamil Alhassbalawi  1 , Mojtaba Zare Ebrahimabad  2 , Fakhri Sadat Seyedhosseini  3 , Yasser Bagheri  1 , Nafiseh Abdollahi  4 , Alireza Nazari  5 , Saeed Mohammadi  6   7 , Yaghoub Yazdani  3
Affiliations

Circulating miR-21 Overexpression Correlates with PDCD4 and IL-10 in Systemic Lupus Erythematosus (SLE): A Promising Diagnostic and Prognostic Biomarker

Nibras Kamil Alhassbalawi et al. Rep Biochem Mol Biol. 2023 Jul.

Abstract

Background: Systemic Lupus Erythematosus (SLE) is a chronic autoimmune condition that affects multiple organs significantly impacts morbidity and mortality. The development of SLE is influenced by genetic predisposition and dysregulated immune response. Our objective was to investigate miR-21, IL-10, and PDCD4 expression in SLE patient plasma and analyze their correlations and potential diagnostic and prognostic values.

Methods: The study included 100 healthy subjects, 50 newly diagnosed (ND), and 50 under-treatment (UT) SLE patients. The patients were observed for 24 weeks to track relapses. miR-21 and PDCD4 gene expression levels were measured using real-time RT-PCR, and IL-10 production was measured using ELISA.

Results: miR-21 and IL-10 expression levels were significantly greater in SLE patients than in healthy subjects, with the highest levels observed in ND patients. PDCD4 expression was also significantly greater in SLE patients than in subjects, with the highest levels observed in UT patients. ROC curve analyses and Cox-Mantel Log-rank tests indicated miR-21, PDCD4, and IL-10 as proper diagnostic and prognostic biomarkers for SLE. The study also revealed a significant positive correlation between miR-21 and PDCD4 and IL-10 levels in SLE patients.

Conclusions: The studies suggest that dysregulation of miR-21, PDCD4, and IL-10 in patients with SLE may contribute to disease development and provides new diagnostic and prognostic markers. Additionally, the observed correlation between miR-21, PDCD4, and IL-10 levels in SLE patients signifies a potential interplay between these molecules.

Keywords: Interleukin-10 (IL-10); Microrna-21 (miR-21); Programmed Cell Death 4 Protein (PDCD4); Systemic Lupus Erythematosus (SLE).

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Conflict of interest statement

We disclose that we have no conflicts of interest.

Figures

Fig. 1
Fig. 1
miR-21, PDCD4, and IL-10 expression in SLE patients and healthy subjects. miR21 expression was significantly greater in SLE patients (PAT.) than in healthy subjects (H.S.) (A). miR21 expression was significantly greater in newly diagnosed (N.D.) SLE patients than in those under treatment (U.T.) (P< 0.01) and healthy subjects (H.S.) (P< 0.001) (B). PDCD4 expression was significantly greater in PAT than in H.S) (P< 0,001) (C). PDCD4 expression was significantly greater in U.T. patients than in H.S. (P< 0.0001) and N.D. patients (P< 0.01) (D). IL-10 was significantly greater in PAT. than in H.S. (E). IL-10 expression was significantly greater in N.D. than in U.T. patients (P< 0.01) and H.S. (P< 0.0001) (F). Comparisons between two groups used the Independent Samples t-Test or Mann-Whitney U test, while comparisons between more than two groups used one-way ANOVA with Tukey's post-test or Kruskal-Wallis with Dunn-Bonferroni post-test. Error bars demonstrate means ± SD (standard deviation). **P< 0.01, ****P< 0.0001.
Fig. 2
Fig. 2
Diagnostic utilities of miR-21, PDCD4, and IL-10 in SLE patients. We conducted ROC curve analyses to evaluate the diagnostic abilities of miR21, PDCD4, and IL-10 to distinguish between SLE patients (PAT.) and healthy subjects (H.S.), as well as newly diagnosed (N.D.) SLE patients and those under treatment (U.T.). miR-21 (A) had high accuracy with an AUC of 0.9924, while PDCD4 had low accuracy with an AUC of 0.5719 (C) in distinguishing between SLE patients and healthy subjects. In terms of distinguishing between N.D. and U.T. patients, miR-21 (B) had an AUC of 0.7140, while PDCD4 had an AUC of 0.9984 (D). IL-10 had good diagnostic accuracy in both tests, with AUCs of 0.9612 (E) and 0.9332 (F), respectively.
Fig. 3
Fig. 3
The correlations of miR21 with PDCD4 and IL-10.We evaluated the correlation between plasma miR-21 expression and IL-10 (A) and PDCD4 (B)s. Pearson correlation showed that IL-10 and miR21 were positively correlated (r = 0.735, P< 0.0001). Our findings also showed that miR21 and PDCD4 were positively, but not significantly, correlated (r = 0.128, P = 0.071).
Fig. 4
Fig. 4
The prognostic utilities of miR-21, PDCD4, and IL-10 to predict flare in SLE patients. The Mantel-Cox log-rank test was conducted to assess the prognostic value of miR21, PDCD4, and IL-10 in predicting flare occurrence over 24 weeks of follow-up. miR-21, PDCD4, and IL-10 all predicted flare occurrences after 24 weeks (A, B, and C, respectively).
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