Clinical Therapeutic Targets Research Articles

Long Noncoding RNAs in Myocardial Ischemia‐Reperfusion Injury

Following an acute myocardial infarction, reperfusion therapy is currently the most effective way to save the ischemic myocardium; however, restoring blood flow may lead to a myocardial ischemia-reperfusion injury (MIRI). Recent studies have confirmed that long-chain noncoding RNAs (LncRNAs) play important roles in the pathophysiology of MIRIs. These LncRNA-mediated roles include cardiomyocyte apoptosis, autophagy, necrosis, oxidative stress, inflammation, mitochondrial dysfunction, and calcium overload, which are regulated through the expression of target genes. Thus, LncRNAs may be used as clinical diagnostic markers and therapeutic targets to treat or prevent MIRI. This review evaluates the research on LncRNAs involved in MIRIs and provides new ideas for preventing and treating this type of injury.

Identification of biomarkers related to Tumor-Infiltrating Lymphocytes (TILs) infiltration with gene co-expression network in colorectal cancer

ABSTRACT Colorectal cancer (CRC) is one of the most common tumors, ranking second in the global cause of death from cancer. The prognosis of advanced patients is still very poor. In this study, hub modules with the highest association with tumor-infiltrating immune cells were identified by weighted gene co-expression network analysis based on CRC expression data from the Gene Expression Omnibus database. Next, three hub genes (ADAM8, IL-1A, VAV3) related to infiltrating immune cells were identified by co-expression network and prognostic analysis. After analysis and verification of the TIMER database, ADAM8 was selected as a prognostic biomarker. Finally, the result of functional test showed that ADAM8 gene expression down-regulation partially reversed the immune tolerance of CRC cells to TILs. By bioinformatics analysis methods and the experimental techniques, we identified ADAM8 as a prognostic biomarker and clinical therapeutic target related to tumor-infiltrating immune cells in CRC.

Single-cell RNA-seq reveals invasive trajectory and determines cancer stem cell-related prognostic genes in pancreatic cancer

ABSTRACT Pancreatic duct adenocarcinoma (PDAC) is an aggressive and lethal malignancy. Pancreatic cancer stem cells (PCSCs) are assumed to contribute to the initiation and invasion of PDAC. In this study, we performed single-cell RNA sequencing (scRNA-seq) analysis of PDAC tumor samples from patients and control pancreas tissues to reveal the transformation process of cancer stem cell (CSC)-like ductal cells into ductal cells with invasive potential and we screened out CSC-related genes (CRGs). Subsequently, we applied LASSO and Cox regression models to identify five CRGs with potential prognostic values and constructed a risk prognostic model using the Cancer Genome Atlas datasets. The risk models were verified using Gene Expression Omnibus datasets. Patients in the high-risk group had a significantly poor overall survival (Pvalue<0.0001), as illustrated by the Kaplan-Meier survival curve, and the area under the curve confirmed the accuracy of predictions by our risk model. Tumor mutation burden variations were used to further explore the differences between the two risk cohorts. In addition, the Human Protein Atlas was used to investigate the protein expression of five hub CRGs. In brief, we utilized scRNA-seq to reveal the invasive trajectory of ductal cells and identified crucial CRGs in PDAC, which may help predict patient survival and provide potential clinical therapeutic targets against CSCs.

SPOCK1/SIX1axis promotes breast cancer progression by activating AKT/mTOR signaling.

SPOCK1 is highly expressed in many types of cancer and has been recognized as a promoter of cancer progression. Its regulatory mechanism in breast cancer (BC) remains unclear. This study aimed to explore the precise function of SPOCK1 in BC progression and to identify the mechanism by which SPOCK1 is involved in cell proliferation and epithelial-mesenchymal transition (EMT). Immunohistochemistry (IHC) experiments and database analysis showed that high expression of SPOCK1 was positively associated with histological grade, lymph node metastasis (LN) and poor clinical prognosis in BC. A series of in vitro and in vivo assays elucidated that altering the SPOCK1 level led to distinct changes in BC cell proliferation and metastasis. Investigations of potential mechanisms revealed that SPOCK1 interacted with SIX1 to enhance cell proliferation, cell cycle progression and EMT by activating the AKT/mTOR pathway, whereas inhibition of the AKT/mTOR pathway or depletion of SIX1 reversed the effects of SPOCK1 overexpression. Furthermore, SPOCK1 and SIX1 were highly expressed in BC and might indicate poor prognoses. Altogether, the SPOCK1/SIX1 axis promoted BC progression by activating the AKT/mTOR pathway to accelerate cell proliferation and promote metastasis in BC, so the SPOCK1/SIX1 axis might be a promising clinical therapeutic target for preventing BC progression.

Microcalcification: A pathological characteristic and mediator of abdominal aortic aneurysm formation

Background and Aims: Abdominal aortic aneurysms (AAAs) are highly lethal diseases without effective clinical predictors and therapeutic targets. Vascular microcalcification as detected by fluorine-18-sodium fluoride (18F-NaF) has recently been recognized as a valuable indicator in predicting of atherosclerotic plaque rupture and AAA expansion. However, whether vascular microcalcification is involved in the pathogenesis of AAA remains elusive.

The Function of SUMOylation and Its Role in the Development of Cancer Cells under Stress Conditions: A Systematic Review.

Malignant tumors still pose serious threats to human health due to their high morbidity and mortality. Recurrence and metastasis are the most important factors affecting patient prognosis. Chemotherapeutic drugs and radiation used to treat these tumors mainly interfere with tumor metabolism, destroy DNA integrity, and inhibit protein synthesis. The upregulation of small ubiquitin-like modifier (SUMO) is a prevalent posttranslational modification (PTM) in various cancers and plays a critical role in tumor development. The dysregulation of SUMOylation can protect cancer cells from stresses exerted by external or internal stimuli. SUMOylation is a dynamic process finely regulated by SUMOylation enzymes and proteases to maintain a balance between SUMOylation and deSUMOylation. An increasing number of studies have reported that SUMOylation imbalance may contribute to cancer development, including metastasis, angiogenesis, invasion, and proliferation. High level of SUMOylation is required for cancer cells to survive internal or external stresses. Downregulation of SUMOylation may inhibit the development of cancer, making it an important potential clinical therapeutic target. Some studies have already begun to treat tumors by inhibiting the expression of SUMOylation family members, including SUMO E1 or E2. The tumor cells become more aggressive under internal and external stresses. The prevention of tumor development, metastasis, recurrence, and radiochemotherapy resistance by attenuating SUMOylation requires further exploration. This review focused on SUMOylation in tumor cells to discuss its effects on tumor suppressor proteins and oncoproteins as well as classical tumor pathways to identify new insights for cancer clinical therapy.

Pan-cancer analysis identifies ESM1 as a novel oncogene for esophageal cancer.

Recent studies highlight the crucial role of endothelial cell-specific molecule 1 (ESM1) in the development of multiple cancer types. However, its aberrant expression and prognostic value in human pan-cancer have largely not been described. In this study, we used The Cancer Genome Atlas (TCGA) analysis databases to explore the expression level and prognostic significance of ESM1 in 33 types of human cancer. ESM1 was shown to be over-expressed in 12 cancer types, including BLCA, BRCA, COAD, CHOL, ESCA, HNSC, KIRC, KICH, LIHC, STAD, THCA, and UCEC. The expression of ESM1 was significantly correlated with the overall survival (OS) of patients in CESC, ESCA, KIRC, and KIRP. In addition, high ESM1 level indicated poor disease-free survival (DFS) of patients with ACC, ESCA, PRAD, LIHC, KIRP, and UCS. Through comparative analysis, we discovered that ESM1 was dramatically up-regulated in esophageal cancer (ESCA) and associated with worse patient OS and DFS. The elevation of ESM1 in ESCA was confirmed by the datasets from Cancer RNA-Seq Nexus (CRN) and Gene Expression Omnibus (GEO). Based on Gene Set Enrichment Analysis (GSEA), we analyzed the co-expressed genes of ESM1 in ESCA, and found that ESM1 was closely implicated in cell proliferation and migration and the regulation of Janus kinase (JAK) signaling pathway. Functionally, knockdown of ESM1 significantly suppressed cell proliferation and migration, and decreased the protein level of JAK1. Taken together, our results suggest for the first time that ESM1 functions as an oncogene and may be a clinical biomarker and/or therapeutic target in ESCA.

Emerging Roles of microRNAs as Biomarkers and Therapeutic Targets for Diabetic Neuropathy.

Diabetic neuropathy (DN) is the most prevalent chronic complication of diabetes mellitus. The exact pathophysiological mechanisms of DN are unclear; however, communication network dysfunction among axons, Schwann cells, and the microvascular endothelium likely play an important role in the development of DN. Mounting evidence suggests that microRNAs (miRNAs) act as messengers that facilitate intercellular communication and may contribute to the pathogenesis of DN. Deregulation of miRNAs is among the initial molecular alterations observed in diabetics. As such, miRNAs hold promise as biomarkers and therapeutic targets. In preclinical studies, miRNA-based treatment of DN has shown evidence of therapeutic potential. But this therapy has been hampered by miRNA instability, targeting specificity, and potential toxicities. Recent findings reveal that when packaged within extracellular vesicles, miRNAs are resistant to degradation, and their delivery efficiency and therapeutic potential is markedly enhanced. Here, we review the latest research progress on the roles of miRNAs as biomarkers and as potential clinical therapeutic targets in DN. We also discuss the promise of exosomal miRNAs as therapeutics and provide recommendations for future research on miRNA-based medicine.

Metabolism and immunity in breast cancer

Breast cancer is one of the most common malignancies that seriously threaten women's health. In the process of the malignant transformation of breast cancer, metabolic reprogramming and immune evasion represent the two main fascinating characteristics of cancer and facilitate cancer cell proliferation. Breast cancer cells generate energy through increased glucose metabolism. Lipid metabolism contributes to biological signal pathways and forms cell membranes except energy generation. Amino acids act as basic protein units and metabolic regulators in supporting cell growth. For tumor-associated immunity, poor immunogenicity and heightened immunosuppression cause breast cancer cells to evade the host's immune system. For the past few years, the complex mechanisms of metabolic reprogramming and immune evasion are deeply investigated, and the genes involved in these processes are used as clinical therapeutic targets for breast cancer. Here, we review the recent findings related to abnormal metabolism and immune characteristics, regulatory mechanisms, their links, and relevant therapeutic strategies.

Protein Tyrosine Phosphatase Receptor S Acts as a Metastatic Suppressor in Malignant Peripheral Nerve Sheath Tumor via Profilin 1-Induced Epithelial-Mesenchymal Transition.

Malignant peripheral nerve sheath tumors (MPNST) are aggressive sarcomas with over half of cases developed in the context of neurofibromatosis type 1. Surgical resection is the only effective therapy for MPNST. The prognosis is very dismal once recurrence or metastasis occurs. Epithelial-mesenchymal transition (EMT) is a key process of recurrence and metastasis involving reorganizations of the actin cytoskeleton and actin-binding proteins (ABP) play a non-negligible role. Protein tyrosine phosphatase receptor S (PTPRS), a tumor suppressor previously reported in colorectal cancer, hepatocellular carcinoma and head and neck cancer, is thought to mediate cell migration and invasion by downregulation of EMT. However, its role in MPNST remains unknown. In the present study, by using tissue microarray we demonstrated low expression of PTPRS was related to poor prognosis in MPNST. Knockdown of PTPRS in MPNST cell lines increased migration/invasion and EMT processes were induced with increased N-cadherin and decreased E-cadherin, which indicated PTPRS may serve as a tumor suppressor in MPNST. In addition, we tested all EMT related ABP and found profilin 1 was significantly elevated in PTPRS downregulated MPNST cell lines. As a member of actin-binding proteins, profilins are regulators of actin polymerization and contribute to cell motility and invasion, which have been reported to be responsible for EMT. Moreover, results showed that downregulation of profilin 1 could restore the EMT processes caused by PTPRS downregulation in vitro and in vivo. Furthermore, high expression of profilin 1 was significantly associated with dismal prognosis. These results highlighted PTPRS served as a potential tumor suppressor in the recurrence and metastasis of MPNST via profilin 1 induced EMT processes and it might provide potential targets for future clinical therapeutics.

MiR-455-3p downregulation facilitates cell proliferation and invasion and predicts poor prognosis of osteosarcoma

BackgroundOsteosarcoma (OS) is one of the most primary malignant bone tumors, mainly attracting children and young adults. The microRNAs are mentioned to play vital roles in many cancers, including OS. The purpose of this study was to explore the expression and function of miR-455-3p in OS and predict the potential effects in clinical diagnosis and prognosis.MethodWe conducted quantitative real-time PCR to assess the expression of miR-455-3p in OS tissues and cell lines. The Cell Counting Kit-8 assay, Transwell assay, and flow cytometry were performed to assess the ability of miR-455-3p on cell proliferation, migration, invasion, and apoptosis. Kaplan–Meier curve and Cox regression analysis were used to demonstrate the survival outcome.ResultsThis study revealed that the expression of miR-455-3p was decreased in OS tissues and cell lines. The dysregulation of miR-455-3p was in association with tumor size, distant metastasis, and clinical stage. Patients with high miR-455-3p expression had a satisfying survival rate. Multivariate Cox analysis indicated that miR-455-3p was a promising prognostic indicator. Expression of miR-455-3p could inhibit the proliferation, migration, and invasion, and facilitate apoptosis of OS cells in vitro.ConclusionThese results indicated the miR-455-3p was a potential clinical therapeutic target and prognostic biomarker by suppressing the proliferation, migration, and invasion, as well as enhancing cell apoptosis.

High expression of WISP1 promotes metastasis and predicts poor prognosis in hepatocellular carcinoma.

The aim of this study was to explore the expression level of Wnt1-inducible signaling pathway protein 1 (WISP1) and its clinical significance in hepatocellular carcinoma (HCC). Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was performed to detect the expression level of WISP1 in HCC tissues and cells. Kaplan-Meier curves and Cox proportional hazard regression model were chosen for single and multiple factor analysis of survival analysis, respectively. Furthermore, wound healing assay and transwell assay were used to verify the effect of WISP1 on HCC cell metastasis in vitro. The expression level of WISP1 in HCC tissues was significantly higher than that in para-cancer tissues (p<0.05). WISP1 expression was positively correlated with lymph node metastasis and clinical stage of HCC. Kaplan-Meier curve showed that HCC patients with higher WISP1 expression exhibited significantly worse progression free survival (PFS) time and overall survival (OS) time. Both univariate and multivariate analysis indicated that high expression of WISP1 was an independent predictor of poor prognosis in HCC. In addition, WISP1 significantly promoted the invasion and migration of HCC cells in vitro. WISP1 might contribute to the development of HCC, serving as a clinical biomarker and therapeutic target for HCC patients.

Extracellular Vesicle-Mediated Vascular Cell Communications in Hypertension: Mechanism Insights and Therapeutic Potential of ncRNAs.

Hypertension, a chronic and progressive disease, is an outstanding public health issue that affects nearly 40% of the adults worldwide. The increasing prevalence of hypertension is one of the leading causes of cardiovascular morbidity and mortality. Despite of the available treatment medications, an increasing number of hypertensive individuals continues to have uncontrolled blood pressure. In the vasculature, endothelial cells, vascular smooth muscle cells (VSMCs), and adventitial fibroblasts play a fundamental role in vascular homeostasis. The aberrant interactions between vascular cells might lead to hypertension and vascular remodeling. Identification of the precise mechanisms of vascular remodeling may be highly required to develop effective therapeutic approaches for hypertension. Recently, extracellular vesicle-mediated transfer of proteins or noncoding RNAs (ncRNAs) between vascular cells holds promise for the treatment of hypertension. Especially, extracellular vesicle-packaging ncRNAs have gained enormous attention of basic and clinical scientists because of their tremendous potential to act as novel clinical biomarkers and therapeutic targets of hypertension. Here we will discuss the current findings focusing on the emerging roles of extracellular vesicle-carrying ncRNAs in the pathologies of hypertension and its associated vascular remodeling. Furthermore, we will highlight the potential of extracellular vesicles and ncRNAs as biomarkers and therapeutic targets for hypertension. The future research directions on the challenges and perspectives of extracellular vesicles and ncRNAs in hypertensive vascular remodeling are also proposed.

Expression and Prognostic Significance of the MMP Family Molecules in Bladder Cancer.

Bladder cancer (BC) is the 10th most common cancer worldwide with significantly varied prognosis in different pathological subtypes. MMPs, a group of enzymes, could involve in the invasion and metastasis of numerous malignancies. The function of MMPs in BC is partly reported in several studies but with great conflicts; hence, a systematic analysis of expression levels and prognostic values of these MMP genes are still to be determined. Firstly, differentially expressed genes (DEGs) of MMPs were identified in ONCOMINE, GEPIA, and UALCAN databases, and these DEGs were also detected by real-time RT-qPCR. More importantly, we investigated the clinical significance of these DEGs in BC patients via Kaplan- Meier (KM) Plotter, UALCAN, and cBioPortal databases. The study found that the mRNA expression of MMP1/11 in BC samples was significantly higher than that in normal bladder tissues, and MMP2/3 was lower in the former than in the latter. The expression level of MMP1/2/7/9/11/13/23B was significantly related to the tumor stages. Furthermore, the prognostic analysis suggested that the high transcription levels of MMP7 and low transcription levels of MMP23A were correlated with favorable relapse-free survival and overall survival in the patients with BC, respectively. Notably, high MMP11/13 expression levels indicated poor overall survival (OS) and relapse-free survival (RFS) in patients with BC. This study revealed that MMP1/2/3/7/9/11/13/23A/23B are possible prognostic biomarkers and clinical therapeutic targets for patients with BC.

Cytokines and inflammatory mediators as promising markers of polymyositis/dermatomyositis.

Idiopathic inflammatory myopathies (IIMs), known also as myositis, represent challenging group of heterogeneous muscle disorders characterized by symmetric proximal muscle weakness and evidence of muscle inflammation. The purpose of this review is to provide important updates on cytokines and inflammatory mediators related to myositis. In the past 5 years, multiple studies brought a fresh insight into the pathogenesis of myositis by introducing new factors or further characterizing the role of the well established mediators in myositis. Among the mediators reviewed in this article, special attention was paid to interferons, C-X-C motif chemokine ligand 10, interleukin-18 and the IL23/Th17 axis. Some of the recent work has also focused on the nontraditional cytokines, such as adipokines, myokines, S100 proteins, High Mobility Group Box 1 or B-cell activating factor and on several anti-inflammatory mediators. Moreover, microRNAs and their potential to reflect the disease activity or to regulate the inflammatory processes in myositis have recently been subject of intensive investigation. Some of the above-mentioned mediators have been proposed as promising clinical biomarkers or therapeutic targets for myositis. Several recent studies contributed to a better understanding of the pathogenesis of myositis and highlighted the clinical significance of certain inflammatory mediators. Application of these new findings may help to develop innovative approaches for patients' phenotyping, disease activity monitoring and potentially novel therapies.

The effects of progenitor and differentiated cells on ectopic calcification of engineered vascular tissues

Ectopic vascular calcification associated with aging, diabetes mellitus, atherosclerosis, and chronic kidney disease is a considerable risk factor for cardiovascular events and death. Although vascular smooth muscle cells are primarily implicated in calcification, the role of progenitor cells is less known. In this study, we engineered tubular vascular tissues from embryonic multipotent mesenchymal progenitor cells either without differentiating or after differentiating them into smooth muscle cells and studied ectopic calcification through targeted gene analysis. Tissues derived from both differentiated and undifferentiated cells calcified in response to hyperphosphatemic inorganic phosphate (Pi) treatment suggesting that a single cell-type (progenitor cells or differentiated cells) may not be the sole cause of the process. We also demonstrated that Vitamin K, which is the matrix gla protein activator, had a protective role against calcification in engineered vascular tissues. Addition of partially-soluble elastin upregulated osteogenic marker genes suggesting a calcification process. Furthermore, partially-soluble elastin downregulated smooth muscle myosin heavy chain (Myh11) gene which is a late-stage differentiation marker. This latter point, in turn, suggests that SMC may be switching into a synthetic phenotype which is one feature of vascular calcification. Taken together, our approach presents a valuable tool to study ectopic calcification and associated gene expressions relevant to clinical therapeutic targets.

Targeting BC200/miR218-5p Signaling Axis for Overcoming Temozolomide Resistance and Suppressing Glioma Stemness.

Background: Glioblastoma (GB) is one of the most common (~30%) and lethal cancers of the central nervous system. Although new therapies are emerging, chemoresistance to treatment is one of the major challenges in cancer treatment. Brain cytoplasmic 200 (BC200) RNA, also known as BCYRN1, is a long noncoding RNA (lncRNA) that has recently emerged as one of the crucial members of the lncRNA family. BC200 atypical expression is observed in many human cancers. BC200 expression is higher in invasive cancers than in benign tumors. However, the clinical significance of BC200 and its effect on GB multiforme is still unexplored and remains unclear. Methods: BC200 expression in GB patients and cell lines were investigated through RT-qPCR, immunoblotting, and immunohistochemistry analysis. The biological importance of BC200 was investigated in vitro and in vivo through knockdown and overexpression. Bioinformatic analysis was performed to determine miRNAs associated with BC200 RNA. Results: Our findings revealed that in GB patients, BC200 RNA expression was higher in blood and tumor tissues than in normal tissues. BC200 RNA expression have a statistically significant difference between the IDH1 and P53 status. Moreover, the BC200 RNA expression was higher than both p53, a prognostic marker of glioma, and Ki-67, a reliable indicator of tumor cell proliferation activity. Overexpression and silencing of BC200 RNA both in vitro and in vivo significantly modulated the proliferation, self-renewal, pluripotency, and temozolomide (TMZ) chemo-resistance of GB cells. It was found that the expressions of BC200 were up-regulated and that of miR-218-5p were down-regulated in GB tissues and cells. miR-218-5p inhibited the expression of BC200. Conclusions: This study is the first to show that the molecular mechanism of BC200 promotes GB oncogenicity and TMZ resistance through miR-218-5p expression modulation. Thus, the noncoding RNA BC200/miR-218-5p signaling circuit is a potential clinical biomarker or therapeutic target for GB.

Effects of lncRNA MALAT1 and lncRNA NKILA on proliferation, invasion and apoptosis of retinoblastoma.

To assess the expression of LncRNA NKILA and MALAT1 in retinoblastoma and its related mechanisms. Tixty-eight cases of retinoblastoma patients admitted to our hospital from February 2017 to February 2019 were collected as a research group, while 70 healthy people who came to our hospital for checkup at the same time were chosen as a control group. Both retinoblastoma and human colorectal mucosa cells were purchased, expression and clinical value of NKILA and MALAT1 in serum of Rb patients were tested, and sh-NKILA, si-NKILA, NC, sh-MALAT1 and si-MALAT1 were transfected into Weri-Rb1 and Y79 cells. qRT-PCR was adopted to detect the NKILA and MALAT1 levels in samples, and WB was adopted to detect the cle-caspase-3, cle-caspase-9, Bax, Cyclin B1, CDC2 and p-CDC2 protein levels in cells. Cell proliferation was conducted via MTT assay, invasion was carried out through transwell assay, and apoptosis was confirmed by flow cytometry assay. NKILA and MALAT1 were low expressed in retinoblastoma, and AUC of LncRNA NKILA and MALAT1 was over 0.8. LncRNA NKILA and MALAT1 were associated with tumor size, classification and clinical grading in children with retinoblastoma. Over-expression of NKILA and MALAT1 could promote apoptosis, inhibit cell growth and Bcl-2 protein, and promote upregulation of the expression levels of clecaspase-3, clecaspase-9 and Bax. By regulating MALAT1 and NKILA, we controlled the growth and apoptosis of Rb cells, which was expected to be a potential clinical therapeutic target for Rb.

Point-of-care testing of protein biomarkers by integrating a personal glucose meter with a concatenated DNA amplifier

Considering most clinical biomarkers and therapeutic targets are proteins, developing point-of-care testing (POCT) of protein biomarkers will be not only greatly beneficial to patients, but also helpful for promoting medical development. In this work, we have proposed a versatile biosensor for the POCT of protein disease biomarkers by integrating the most technology-matured POCT device, i.e., personal glucose meter (PGM) with a concatenated DNA amplifier. In order to convert protein targets into cascaded glucose production, the concatenated DNA amplifier is fabricated by a catalytic hairpin assembly (CHA) reaction and a hybridization chain reaction (HCR), which is simplified as CHA-HCR system. As a “plug-and-play” converter and amplifier, the integrated CHA-HCR system can be immediately initiated by the detected protein target, resulting in dynamic DNA assembly-directed invertase polymerization on Au-Fe3O4 nanoparticles for cascaded glucose production. With the advantages of programmable conversion strategy, high conversion efficacy, anti-interference, specificity, and sensitivity, the capability of this system has been demonstrated by the quantification of several protein biomarkers in serum, including anti-digoxin antibody, thrombin, and anti-HCV antibody. Therefore, it can provide a universal and rational toolbox to develop more POCT device-based biosensors for the detection of disease-related biomarkers other than glucose in complex matrices.

Non‑coding RNAs that regulate the Wnt/β‑catenin signaling pathway in gastric cancer: Good cop, bad cop? (Review).

Gastric cancer (GC) is one of the most common causes of cancer‑related mortality worldwide. Despite remarkable progress in the diagnosis and treatment of GC, a large number of cases are diagnosed as advanced GC, and treatment failure occurs. Emerging evidence has shown that non‑coding RNAs (ncRNAs), especially microRNAs (miRNAs) and long non‑coding RNAs (lncRNAs), play a vital role in the tumorigenesis and development of GC. Moreover, the pathogenesis of GC is closely related to aberrant activation of the Wnt (Wingless‑type MMTV integration site family) signaling pathway. ncRNAs serve as potential novel biomarkers in the clinical examination, prognosis and therapeutic targeting of GC. Furthermore, dysregulation of ncRNAs has been demonstrated to affect tumor initiation, epithelial‑mesenchymal transition (EMT), angiogenesis, tumor development, invasion, metastasis and resistance to therapy via the Wnt/β‑catenin signaling pathway. This review focuses on the role of ncRNAs in modulating the Wnt/β‑catenin signaling pathway in the pathogenesis of GC, which may provide a reference for the clinical diagnosis and treatment of GC.