The MALAT1-H19/miR-19b-3p axis can be a fingerprint for diabetic neuropathy

Abstract

Background: Diabetic neuropathy (DN) is one of the most common microvascular complications of diabetes that is attributed to impaired immune regulation. In this study, we first examined the expression of long non-coding (lncRNAs) MALAT1 and H19, and their downstream microRNAs (miRNAs) miR-19b-3p, miR-125a-5p, and then assayed the mRNA expression of downstream targets of these miRNAs, including SEMA4C, SEMA4D, PLXNB2, ATG14, and ATG16L1. Methods: Peripheral blood samples were obtained from 20 DN patients, 20 diabetic patients without neuropathy (non-DN), and 10 healthy controls (HC). The expression levels of lncRNAs, miRNAs, and target genes were evaluated in whole blood using Real-time PCR. Results: Upregulation of MALAT1, H19, SEMA4C, PLXNB2, and ATG16L1 and downregulation of miR-19b-3p was seen in the DN group compared to the non-DN and HC groups. Non-DN patients had significantly lower expression levels of miR-125a-5p, SEMA4D, ATG14, and ATG16L1 compared to the HC. MALAT1 and H19 had a positive correlation with each other and had a negative correlation with the expression of miR-19b-3p. Expression levels of SEMA4C, SEMA4D, PLXNB2, and ATG16L1 were positively correlated with each other as well as lncRNAs expression. Receiver operating characteristic (ROC) analysis showed Area under the curve (AUC) = 0.9226 for MALAT1, AUC= 0.9248 for H19, and AUC= 0.7683 for miR-19b-3p. Conclusion: The MALAT1-H19/miR-19b-3p axis might be involved in the development of DN and these molecules could be useful biomarkers for DN. Dysregulated expression of SEMA4C, PLXNB2, and ATG16L1, targeted by miR-19b-3p and miR-125a-5p, showed that they probably play a role in the DN development.