Long noncoding RNA (MEG3) in urinal exosomes functions as a biomarker for the diagnosis of Hunner‐type interstitial cystitis (HIC)

Abstract

Background Toll‐like receptor‐7 (TLR7) is functionally involved in the pathogenesis of Hunner‐type interstitial cystitis (HIC). In addition, maternally expressed gene 3 (MEG3) is implicated in many urethral diseases. In this study, we aimed to verify the hypothesis that exosomal MEG3 in urine can be used as a novel diagnostic biomarker for HIC. Methods Electron microscopy was utilized to observe the distribution of urinary exosomes between the case group and the control group. Receiver operating characteristic analysis was utilized to compare the diagnostic values of MEG3 and miR‐19a‐3p. Computational analysis and luciferase assay were conducted to identify the correlation between MEG3 and miR‐19a‐3p as well as between TLR7 and miR‐19a‐3p. In addition, real‐time polymerase chain reaction and Western blot were performed to establish the signaling pathways implicated in the pathogenesis of HIC. Results When age and gender distributions are excluded, urinary exosomes were equally distributed between case and control groups. The area under the curve of MEG3 was larger than that of miR‐19a‐3p, indicating that MEG3 has a better value in the diagnosis of HIC. In addition, patients with HIC showed elevated MEG3 expression and inhibited miR‐19a‐3p expression, thus establishing a negative correlation between MEG3 and miR‐19a‐3p. MEG3 and TLR7 were both identified as targets of miR‐19a‐3p, establishing a MEG3/miR‐19a‐3p/TLR7 signaling pathway, in which MEG3 enhances the expression of TLR7 via inhibiting the expression of miR‐19a‐3p. Conclusion MEG3 level was upregulated in patients with HIC. In addition, MEG3 downregulated miR‐19a‐3p expression while upregulating TLR7 expression. Furthermore, MEG3 contributes to the pathogenesis of HIC. Therefore, exosomal MEG3 in urine can be used as a biomarker for HIC diagnosis.

Exploration of the core genes in ulcerative interstitial cystitis/bladder pain syndrome

“…The up-regulated DEGs were mainly enriched in the extracellular region, extracellular space, and external side of the plasma membrane, while the down-regulated DEGs were mainly enriched in the extracellular exosome, apical plasma membrane, and bicellular tight junction. Some studies have suggested that the long noncoding RNA MEG3 in urine exosomes can be used as a biomarker for IC/ BPS (16). Stellavato et al (17) suggested that continuous loss of extracellular matrix may be related to inflammation in IC/BPS.…”

Exosomal Long Non-Coding RNAs in Lung Diseases

“…Exosomal MEG3: From the PubMed screening, we found no studies on MEG3 associated with lung diseases and exosomes. However, three recent studies could describe exosomal MEG3 in high-grade serous carcinoma [163], cervical cancer [164], and Hunner-type interstitial cystitis [165]. These studies underline that MEG3 may be involved in intercellular communication, especially in cancers, and therefore further research on this topic is needed to assess its relevance in lung diseases.…”

“…First, these lncRNAs may trigger important hallmarks of cancers, such as "Genome instability and mutation" for CDKN2B-AS1 [87,121], "Activating invasion and metastasis" for FENDRR [196], "Resisting cell death" for MEG3 and CDKN2B-AS1 [118,154,157,160,207], and "Sustaining and proliferative signaling" for TUG1 [83]. Secondly, previous studies in other cancers found an exosomal expression of MEG3, TUG1, and CDKN2B-AS1 [163][164][165]201,202,215]. These findings suggest that MEG3, TUG1, and CDKN2B-AS1 may also be involved in lung cancer intercellular communication.…”

Decreased Excretion of Urinary Exosomal Aquaporin-2 in a Puromycin Aminonucleoside-Induced Nephrotic Syndrome Model

“…Accumulative evidence has indicated that the relative abundance of these molecule-bearing urinary exosomes is altered in various kidney diseases [7]. In fact, it has been proposed that several exosome-derived molecules, such as aquaporins (AQPs) [8], miR-125a and miR-351 [6], RNA (MEG3) [9], RNA HOTAIR [4], and fetuin-A, could have potential application as biomarkers [10].…”