<p>Plasma Exosomal miR-146b-5p and miR-222-3p are Potential Biomarkers for Lymph Node Metastasis in Papillary Thyroid Carcinomas</p>

Abstract

Background: Lymph node metastasis (LNM) is associated with increased risk of recurrence and poor prognosis in papillary thyroid cancer (PTC). Novel non-invasive biomarkers for the prediction of LNM in PTC patients are still urgently needed. In this study, the relationship between the expression of plasma exosomal microRNAs (miRNAs) and LNM was analyzed. Further, we aimed to explore if exosomal miRNAs can serve as indicators of LNM in PTC patients. Methods: A total of 64 PTC patients who underwent total thyroidectomy and neck dissection from June 2018 to July 2018 in West China Hospital were enrolled in this study. Plasma exosomes were isolated by exoRNeasy Serum/Plasma Maxi Kit. The levels of selected exosomal miRNAs were detected by real-time quantitative PCR (qRT-PCR). Cox proportional hazard analyses and receiver operating characteristic (ROC) curves were conducted to evaluate the predictive efficiency. Furthermore, PTC cell lines with transfection of miRNA mimics/inhibitors were used to verify the functions of exosomal miRNAs. Results: 49 PTC patients with LNM and 15 without LNM were included in the present study. Exosomal miR-146b-5p and miR-222-3p were both significantly upregulated in patients with LNM (P values were 0.008 and 0.015, respectively). ROC analyses revealed that the areas under the curves (AUCs) of miR-146b-5p and miR-222-3p for LNM prediction were 0.811 and 0.834, respectively. Moreover, the AUC increased to 0.895 when the two miRNAs used together. Wound healing assays and transwell assays showed that miR-146b-5p and miR-222-3p significantly enhanced the migration and invasion ability of PTC cells in vitro. Conclusion: Plasma exosomal miR-146b-5p and miR-222-3p could serve as potential biomarkers for LNM in PTC.

Integrative analysis of exosomal microRNA-149-5p in lung adenocarcinoma

“…Up-regulation of exosomal miR-146b-5p and miR-222-3p augmented migration and invasion abilities of papillary thyroid carcinomas [19]. Additionally, it was found that BMMSC-derived exosomal miR-144 suppressed growth of tumor cells and colony formation in NSCLC by targeting CCNE1 and CCNE2 [20].…”

NK cell-derived exosomes carry miR-207 and alleviate depression-like symptoms in mice

“…Exosomal miRNAs can transport epigenetic information, affecting gene expression in a recipient cell [41]. Many studies have demonstrated that exosomal miRNAs can play important roles in treatment or detected markers of many diseases, including cancer progression and metastasis [42,43], neurodegenerative diseases [44][45][46], and inflammation [47], and they also participate in the pathological of depression [48,49]. Furthermore, mesenchymal stem cell-derived exosomal miR26a can improve symptoms of depression in rats [50].…”

The Role of Exosomes in Thyroid Cancer and Their Potential Clinical Application

“…Lee and his collaborator found that the levels of miR-146b and miR-222 in TPC-1 exosomes were higher than those in NTHY cells, indicating that these two miRNAs may be biomarkers for PTC recurrence (57). Interestingly, another study detected plasma exosomes in PTC patients with or without lymph node metastasis (LNM), confirming that circulating exosomal miR-146b-5p and miR-222-3p have high diagnostic value for predicting LNM in PTC patients (58). Although most PTC patients have a good prognosis, LNM often occurs in the early stage, and predicting and diagnosing LNM in advance can prevent patients from experiencing unnecessary pain.…”

“…As mentioned earlier, miR-146b and miR-222, which are relatively abundant in the exosomes of TPC-1 cells, caused a negative proliferative effect on both TPC-1 and NTHY cells (57). Jiang K et al observed that exosomal miR-146b-5p and miR-222-3p were not only associated with LNM but also significantly enhanced the migration and invasion abilities of PTC cells (58). The exosome cargo continuously changes, and the quantity depends on the course of disease progression (75).…”