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This study aims at designing a novel impedimetric aptasensor to determine carcinoembryonic antigen (CEA). The CEA aptasensor was developed by covalent immobilization of an amine-modified CEA aptamer on the surface of a glassy carbon electrode (GCE) which was modified by gold nanoparticles (AuNPs) incorporated in amino-functionalized MCM-41 (AMCM). After the aptamer was immobilized, CEA was incubated on the surface of an Ap-GA-AuNPs/AMCM-GCE. The change in the interfacial charge transfer resistance (R ct ) of the redox marker served as an excellent signal for the quantitative determination of CEA. Cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were used to display the aptamer immobilization on the electrode surface. Through the EIS method, the linear range and the detection limit of CEA were found to be 1.0 × 10 −3 −100.0 ng mL −1 and 9.8 × 10 −4 ng mL −1 respectively. Moreover, the proposed aptasensor was used to determine of CEA in patient and healthy human serum samples and the results indicated that this aptasensor has great potential for practical application which the strength point of this aptasensor.

Uterine leiomyosarcoma (uLMS) is the most common type of uterine sarcoma associated with poor prognosis, high rates of recurrence, and metastasis. There is currently limited information about uLMS molecular mechanisms of origin and development. Bromodomain (BRD)-containing proteins are involved in many biological processes, most notably epigenetic regulation of transcription, and BRD protein dysfunction has been linked to many diseases including tumorigenesis. However, the role of BRD proteins in the pathogenesis of uLMS is unknown. Here, we show for the first time that BRD9 is aberrantly overexpressed in uLMS tissues compared to adjacent myometrium. BRD9 expression is also upregulated in uLMS cell lines compared to benign uterine fibroid and myometrium cell lines. Inhibition of BRD9 using the specific inhibitor (TP-472) suppressed uLMS cell proliferation via inducing apoptosis and cell cycle arrest. To further characterize the mechanistic basis for TP-472 inhibition of uLMS cell growth, we performed a comparative RNA-seq analysis of vehicle-treated and TP-472-treated uLMS cells (n = 4 each). Bioinformatics analysis revealed that TP-472 treatment distinctly altered the uLMS cell transcriptome. Gene set enrichment analysis identified critical pathways altered by BRD9 inhibition, including interferon-alpha response, KRAS signaling, MYC targets, TNF-a signaling via NFkB, and MTORC1 signaling. Parsimonious gene correlation network analysis identified nine enriched modules, including cell cycle and apoptosis modules. Moreover, the ENCODE Histone Modifications gene set and TargetScan microRNA analysis in Enrichr suggested that TP-472-induced BRD9 inhibition may alter the uLMS cell transcriptome by reprograming the oncogenic epigenome and inducing miRNA-mediated gene regulation. Therefore, BRD9 constitutes a specific vulnerability in malignant uLMS, and targeting non-BET BRD proteins in uLMS may provide a promising and novel strategy for treating patients with this aggressive uterine cancer.

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