Serum exosomal hsa_circRNA_0001842 is the potential biomarker for diagnosing lower limb vascular disease in type 2 diabetes mellitus.

This study aimed to identify the potential circular RNAs (circRNAs) in exosomes isolated from serum as biomarkers of lower limb vascular disease (LLVD) in patients with type 2 diabetes mellitus (T2DM). This research collected circRNAs from exosomes isolated from three T2DM patients and three T2DM patients with LLVD for microarray analysis. Five candidate biomarkers derived from differentially expressed circRNAs were then validated by quantitative real-time polymerase chain reaction in 20 T2DM patients and 20 T2DM patients with LLVD. Finally, expression levels of circRNAs were validated in 160 samples. Significant differences in the expression of 295 circRNAs were found between T2DM controls and T2DM patients with LLVD. Among them, 191 differentially expressed circRNAs were upregulated, and 104 were downregulated in T2DM patients with LLVD. Three upregulated and two downregulated circRNAs were further confirmed in 40 samples. According to the testing of 160 samples, hsa_circ_0001842 showed a noticeable specificity in the T2DM patients with LLVD group (n = 80), with an area under the curve (AUC) of 0.79, a sensitivity of 88.75%, and a specificity of 68.75%. In conclusion, hsa_circ_0001842 was found as a potential diagnostic biomarker for T2DM with LLVD.

Overexpression of lncRNA MAPT-AS1 exacerbates cell proliferation and metastasis in breast cancer.

Background: To investigate the function of MAPT antisense RNA 1 (MAPT-AS1) in breast cancer (BC), evaluating its potential diagnostic value for BC patients. Methods: This study involved 498 patients with BC, 222 patients with benign breast diseases, including 74 cases each of of breast fibroadenoma, breast intraductal papilloma, and ductal hyperplasia and 429 healthy controls. We collected 20 cases of BC tissues and adjacent normal tissues and blood was taken from each participant. The expression levels of MAPT-AS1 were detected using reverse transcription polymerase chain reaction (RT-PCR). According to the median serum level of MAPT-AS1, patients were divided into a high expression group and a low expression group. We established MAPT-AS1 overexpression and knockdown in human BC cell line ZR-75-1 and MDA-MB-231 to study the function on cell proliferation [using cell counting kit-8 (CCK-8) assay], migration, and invasion (using Transwell assay). Results: The expression of MAPT-AS1 was significantly up-regulated in tissues and serum of BC patients compared with controls (P<0.0001 for both). Receiver operating characteristic (ROC) curve analysis showed that MAPT-AS1 had a large area under the curve (AUC) of 0.893. The expression of MAPT-AS1 in serum was closely related to the large tumor size, grade, tumor-node-metastasis (TNM) stages, and human epidermal growth factor receptor 2 (HER-2) expression status of BC patients. Overexpression of MAPT-AS1 activated the Wnt/ß-catenin signaling pathway, promoting proliferation, migration, and invasion. Conclusions: Overexpression of MAPT-AS1 in tissues and serum is a reliable diagnostic marker for BC, and MAPT-AS1 regulates the proliferation and metastasis of BC cells by activating the Wnt/ß-catenin signaling pathway.

Exosome-depleted MiR-148a-3p derived from Hepatic Stellate Cells Promotes Tumor Progression via ITGA5/PI3K/Akt Axis in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a major cause of cancer-related death worldwide. Although it has been known that hepatic stellate cells (HSCs) play critical roles in the development and progression of HCC, the molecular mechanism underlying crosstalk between HSCs and cancer cells still remains unclear. Here, we investigated the interactions between HSCs and cancer cells through an indirect co-culture system. The expressions of cellular and exosomal miR-148a-3p were evaluated by quantitative real-time PCR. Cell counting kit-8 was used for evaluating cell growth in vitro. Cell migration and invasion ability were evaluated by wound-healing and Transwell assays. Western blot, quantitative real-time PCR and Luciferase reporter assay were performed to determine the target gene of miR-148a-3p. A xenograft liver cancer model was established to study the function of exosomal miR-148a-3p in vivo. We found that miR-148a-3p was downregulated in co-cultured HSCs and overexpression of miR-148a-3p in HSCs impaired the proliferation and invasiveness of HCC both in vitro and in vivo. Moreover, further study showed that the miR-148a-3p was also downexpressed in HSCs-derived exosomes, and increased HSCs-derived exosomal miR-148a-3p suppressed HCC tumorigenesis through ITGA5/PI3K/Akt pathway. In conclusion, our study demonstrated that exosome-depleted miR-148a-3p derived from activated HSCs accelerates HCC progression through ITGA5/PI3K/Akt axis.