Dysfunction of PTEN-Associated MicroRNA Regulation: Exploring Potential Pathological Links in Type 1 Diabetes Mellitus

Abstract

Background and Objectives: Type 1 Diabetes Mellitus (T1DM) is an autoimmune disease with T cell-mediated pathogenesis of pancreatic β-cell destruction, leading to insulin deficiency. MicroRNAs such as miR-223 and miR-106b, along with PTEN, have been reported to participate in the pathophysiology of diabetes and its complications. The current study has explored the expression of miR-223, miR-106b, and PTEN and their association with various clinical and biochemical parameters in subjects diagnosed with T1DM. Materials and Methods: Sixty T1DM patients (two groups as uncomplicated/ with microalbuminuria) and fifty healthy volunteers, age- and sex-matched, were enrolled in this study. The fasting venous blood samples were collected, and PTEN and miRNAs (miR-223 and miR-106b) levels were measured by ELISA and real-time PCR, respectively. Results: The PTEN levels of patients with microalbuminuria were significantly lower than those of patients without microalbuminuria, while those of miR-223 and miR-106b were significantly increased in the T1DM group compared with the healthy control group (p < 0.001). ROC analysis indicated that PTEN, miR-223, and miR-106b could be potential biomarkers for diagnosing T1DM with high specificity but with variable sensitivities. Also, PTEN and miR-223 were negatively correlated with r =-0.398 and p < 0.0001, indicating that they were interrelated in their role within the T1DM pathophysiology. Conclusions: In the current study, it has been shown that the circulating levels of PTEN, miR-223, and miR-106b are significantly changed in T1DM patients and may back their potential to be used as non-invasive biomarkers for the diagnosis and monitoring of T1DM. Low PTEN protein expression was related to high miR-223 expression, indicating involvement of these miRNA in the regulation of PTEN. Further studies should be performed to clarify the exact mechanisms and possible clinical applications of these molecules.