Trithorax-like group complex containing KDM6A acts antagonistically to Polycomb-repressive complex 2 (PRC2) containing EZH2 in maintaining the dynamics of the repression and activation of gene expression through H3K27 methylation. In urothelial bladder carcinoma, KDM6A (a H3K27 demethylase) is frequently mutated, but its functional consequences and therapeutic targetability remain unknown. About 70% of KDM6A mutations resulted in a total loss of expression and a consequent loss of demethylase function in this cancer type. Further transcriptome analysis found multiple deregulated pathways, especially PRC2/EZH2, in KDM6A-mutated urothelial bladder carcinoma. Chromatin immunoprecipitation sequencing analysis revealed enrichment of H3K27me3 at specific loci in KDM6A-null cells, including PRC2/EZH2 and their downstream targets. Consequently, we targeted EZH2 (an H3K27 methylase) and demonstrated that KDM6A-null urothelial bladder carcinoma cell lines were sensitive to EZH2 inhibition. Loss- and gain-of-function assays confirmed that cells with loss of KDM6A are vulnerable to EZH2. IGFBP3, a direct KDM6A/EZH2/H3K27me3 target, was up-regulated by EZH2 inhibition and contributed to the observed EZH2-dependent growth suppression in KDM6A-null cell lines. EZH2 inhibition delayed tumor onset in KDM6A-null cells and caused regression of KDM6A-null bladder tumors in both patient-derived and cell line xenograft models. In summary, our study demonstrates that inactivating mutations of KDM6A, which are common in urothelial bladder carcinoma, are potentially targetable by inhibiting EZH2.

The screening and diagnosis of cancer are hallmarks of medicine in the aging population. Recently, microRNAs have shown potential for use as biomarkers, which could advance the field of diagnostics. The presence of miRNA-141 in the serum has been well described in several malignancies. However, the invasive approach used for sampling represents the major limitation for its practical application and, hence, its notable absence as a method for screening the general population. In light of this, we aimed to develop a high-sensitivity microRNA (miR) biosensor for application in the diagnosis of all miR-141-associated cancers, such as colorectal cancer (CRC) and breast cancer (BC). The novelty lies in our dual-probe design, which is reliant on the hybridization of the fluorescein isothiocyanate (FITC) targeting probe onto an existing sample of urinary miR-141 in the first step, followed by complementary binding with a biotinylated probe that has been coated on a modified screen-printed carbon electrode (SPCE). The hybridization of the probe and sensor produces signals via the catalytic reduction of H₂O₂ at HRP-modified SPCEs in the presence of H₂O, which was measured by either cyclic voltammetry or chronoamperometry (CA) currents. In our study, the detection and expression of miR-141 in a cohort of colorectal cancer (n = 6) and breast cancer (n = 4) samples showed that its levels were significantly higher than in a healthy cohort (n = 9) (p < 0.004). Moreover, our miR sensor demonstrated high stability, reliability, and sensitivity (p < 0.0001). This work hopefully provides new information for the detection and monitoring of de novo and existing cancers.

Research in cancer diagnostics has recently established its footing and significance in the biosensor sphere, emphasizing the idea of a unique probe design used as a sensor and actuator, to identify the presence of protein, DNA, RNA, or miRNA. The fluorescein isothiocyanate (FITC) probe and biotinylated probe are designed for a two-pronged approach to the detection of the urinary miR-21 and miR-141, both of which have demonstrated significance in the development and progression of colorectal cancer, a leading cause of mortality and morbidity. The remainder of the apparatus is composed of a modified screen-printed carbon electrode (SPCE), to which the probes adhere, that transduces signals via the redox reaction between H₂O₂ and HRP, measured with chronoamperometry and cyclic voltammetry. The precise nature of our ultra-non-invasive biosensor makes for a highly sensitive and practical cancer detector, concluded by the significance when establishing disease presence (miR-21 p-value = 0.0176, miR-141 p-value = 0.0032), disease follow-up (miR-21 p-value = 0.00154, miR141 p-value < 0.0005), and even disease severity. This article hopes to emphasize the potential of an additional clinical tool for the management of colorectal cancer.

Prostate cancer is the most common cancer in the male population, carrying a significant disease burden. PSA is a widely available screening tools for this disease. Current screen-printed carbon electrode (SPCE)-based biosensors use a two-pronged probe approach to capture urinary miRNA. We were able to successfully detect specific exosomal miRNAs (exomiRs) in the urine of patients with prostate cancer, including exomiR-451 and exomiR-21, and used electrochemistry for measurement and analysis. Our results significantly reaffirmed the presence of exomiR-451 in urine and that a CV value higher than 220 nA is capable of identifying the presence of disease (p-value = 0.005). Similar results were further proven by a PAS greater than 4 (p-value = 0.001). Moreover, a higher urinary exomiR-21 was observed in the high-T3b stage; this significantly decreased following tumor removal (p-values were 0.016 and 0.907, respectively). According to analysis of the correlation with tumor metastasis, a higher exomiR-21 was associated with lymphatic metastasis (p-value 0.042), and higher exomiR-461 expression was correlated with tumor stage (p-value 0.031), demonstrating that the present exomiR biosensor can usefully predict tumor progression. In conclusion, this biosensor represents an easy-to-use, non-invasive screening tool that is both sensitive and specific. We strongly believe that this can be used in conjunction with PSA for the screening of prostate cancer.

Due to the severe acute respiratory syndrome coronavirus (SARS-CoV-2, also called coronavirus disease 2019 (COVID-19)) pandemic starting in early 2020, all social activities ceased in order to combat its high transmission rate. Since vaccination combats one aspect for halting the spread of the virus, the biosensor community has looked at another aspect of reducing the burden of the COVID-19 pandemic on society by developing biosensors that incorporate point-of-care (POC) testing and the rapid identification of those affected in order to deploy appropriate measures. In this study, we aim first to propose a screen-printed carbon electrode (SPCE)-based electrochemical biosensor that meets the ASSURED criteria (i.e., affordable, sensitive, specific, user-friendly, rapid, equipment-free, and deliverable) for POC testing, but more importantly, we describe the novelty of our biosensor’s modifiability that uses custom dual probes made from target nucleic acid sequences. Additionally, regarding the sensitivity of the biosensor, the lowest sample concentration was 10 pM (p = 0.0257) without amplification, which might challenge the traditional technique of reverse transcriptase-polymerase chain reaction (RT-PCR). The purpose of this study is to develop a means of diagnostics for the current pandemic as well as to provide an established POC platform for future epidemics.

In this study, we detected the expression levels of miR-21 in 38 clinical urine samples, obtained from 10 patients with PCa (with each sample obtained at three time points: before surgery, 1 month after surgery, and 3 months after surgery), 3 patients with benign prostatic hypertrophy (BPH), and 5 healthy subjects (as a control group). All of the samples were examined using a silver nanoparticle-based biosensor, and the sensitivity of the biosensor was simultaneously confirmed via qRT-PCR. The results were further analyzed together with clinical data such as PSA values and cancer stages. The sensitivity of the biosensor ranged up to 100 fM, and it presented a rather high selectivity rate. Our results indicated a significantly decreased expression level of miR-21 in the patient cases at 3 months post-surgery when compared with pre-surgery levels (p-value < 0.001). In addition, when distinguishing the differences in the expression level of miR-21 between healthy subjects and patients with PCa or BPH, both groups showed highly significant differences (p = 0.008 and p < 0.001, respectively). The results strongly suggest that the proposed miR-21 biosensor can be used as an auxiliary screening tool for the early detection of PCa and may effectively facilitate tracking of the progression of PCa, thus enabling more accurate healthcare decision making.