The construction and experimental verification of a 6-LncRNA model based on Lactic acid metabolism in the tumor microenvironment of Wilms tumor.

BACKGROUND: Lactic acid (LA) can promote the malignant progression of tumors through the crosstalk with the tumor microenvironment (TME). However, the function of long non-coding RNAs (lncRNAs) related to LA metabolism in Wilms tumor (WT) remains unclear. METHODS: Gene expression data and clinical data of WT patients were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Through the ESTIMATE algorithm and Pearson correlation analysis, lncRNAs related to tumor immunity and LA metabolism were screened. Subsequently, Cox regression analysis and Lasso Cox regression analysis were used to construct a model. Furthermore, candidate genes were identified and a competitive endogenous RNA (ceRNA) network was conducted to explore the specific mechanism of characteristic genes. Finally, based on the strong clinical relevance of UNC5B-AS1, its expression and function were experimentally verified. RESULTS: The immune score and stromal score were found to be closely related to the prognosis of WT. Eventually, a prognostic model (TME-LA-LM) consisting of 6 lncRNAs was successfully identified. The model demonstrated favorable predictive ability and accuracy, with significant variation in immune infiltration and drug susceptibility observed between risk groups. Additionally, the study revealed the involvement of 2 candidate genes and 5 microRNAs (miRNAs) in the tumor's development. Notably, UNC5B-AS1 was highly expressed and found to promote the proliferation and migration of tumor cells. CONCLUSION: This study, for the first time, elucidated the prognostic signatures of WT using lncRNAs related to TME and LA metabolism. The fundings of this research offer valuable insights for future studies on immunotherapy, personalized chemotherapy and mechanism research.

Photoswitchable dynamics and RNAi synergist with tailored interface and controlled release reprogramming tumor immunosuppressive niche.

Immunosuppressive tumor microenvironment (ITM) severely limited the efficacy of immunotherapy against triple-negative breast cancer (TNBC). Herein, Apt-LPR, a light-activatable photodynamic therapy (PDT)/RNAi immune synergy-enhancer was constructed by co-loading miR-34a and photosensitizers in cationic liposomes (in phase III clinical trial). Interestingly, the introduction of tumor-specific aptamers creates a special "Liposome-Aptamer-Target" interface, where the aptamers are initially in a "lying down" state but transform to "standing up" after target binding. The interfacing mechanism was elaborately revealed by computational and practical experiments. This unique interface endowed Apt-LPR with neutralized surface potential of cationic liposomes to reduce non-specific cytotoxicity, enhanced DNase resistance to protect aptamers, and preserved target-binding ability for selective drug delivery. Upon near-infrared irradiation, the generated reactive oxygen species would oxidize unsaturated phospholipids to destabilize both liposomes and lysosomes, realizing stepwise lysosomal escape of miR-34a for tumor cell apoptosis and downregulation of PD-L1 to suppress immune escape. Together, tumor-associated antigens released from PDT-damaged mitochondria and endoplasmic reticulum could activate the suppressive immune cells to establish an "immune hot" milieu. The collaborative immune-enhancing strategy effectively aroused systemic antitumor immunity and inhibited primary and distal tumor progression as well as lung metastasis in 4T1 xenografted mouse models. The photo-controlled drug release and specific tumor-targeting capabilities of Apt-LPR were also visualized in MDA-MB-231 xenografted zebrafish models. Therefore, this photoswitchable PDT/RNAi immune stimulator offered a powerful approach to reprogramming ITM and reinforcing cancer immunotherapy efficacy.

A self-powered theranostic DNA nanodevice for amplification of both intracellular microRNA imaging and photodynamic therapy.

While numerous methods exist for diagnosing tumors through the detection of miRNA within tumor cells, few can simultaneously achieve both tumor diagnosis and treatment. In this study, a novel graphene oxide (GO)-based DNA nanodevice (DND), initiated by miRNA, was developed for fluorescence signal amplification imaging and photodynamic therapy in tumor cells. After entering the cells, tumor-associated miRNA drives DND to Catalyzed hairpin self-assembly (CHA). The CHA reaction generated a multitude of DNA Y-type structures, resulting in a substantial amplification of Ce6 fluorescence release and the generation of numerous singlet oxygen (1O2) species induced by laser irradiation, consequently inducing cell apoptosis. In solution, DND exhibited high selectivity and sensitivity to miRNA-21, with a detection limit of 11.47 pM. Furthermore, DND discriminated between normal and tumor cells via fluorescence imaging and specifically generated O21 species in tumor cells upon laser irradiation, resulting in tumor cells apoptosis. The DND offer a new approach for the early diagnosis and timely treatment of malignant tumors.

Enhancing miR-19a/b induced cardiomyocyte proliferation in infarcted hearts by alleviating oxidant stress and controlling miR-19 release.

Fully restoring the lost population of cardiomyocytes and heart function remains the greatest challenge in cardiac repair post myocardial infarction. In this study, a pioneered highly ROS-eliminating hydrogel was designed to enhance miR-19a/b induced cardiomyocyte proliferation by lowering the oxidative stress and continuously releasing miR-19a/b in infarcted myocardium in situ. In vivo lineage tracing revealed that ∼20.47 % of adult cardiomyocytes at the injected sites underwent cell division in MI mice. In MI pig the infarcted size was significantly reduced from 40 % to 18 %, and thereby marked improvement of cardiac function and increased muscle mass. Most importantly, our treatment solved the challenge of animal death--all the treated pigs managed to live until their hearts were harvested at day 50. Therefore, our strategy provides clinical conversion advantages and safety for healing damaged hearts and restoring heart function post MI, which will be a powerful tool to battle cardiovascular diseases in patients.

miRNA-based electrochemical biosensors for ovarian cancer.

Ovarian cancer, a prevalent and deadly cancer among women, presents a significant challenge for early detection due to its heterogeneous nature. MicroRNAs, short non-coding regulatory RNA fragments, play a role in various cellular processes. Aberrant expression of these microRNAs has been observed in the carcinogenesis-related processes of many cancer types. Numerous studies highlight the critical role of microRNAs in the initiation and progression of ovarian cancer. Given their clinical importance and predictive value, there has been considerable interest in developing simple, prompt, and sensitive miRNA biosensor strategies. Among these, electrochemical sensors have demonstrated advantageous characteristics such as simplicity, sensitivity, low cost, and scalability. These microRNA-based electrochemical biosensors are valuable tools for early detection and point-of-care applications. This article discusses the potential role of microRNAs in ovarian cancer and recent advances in the development of electrochemical biosensors for miRNA detection in ovarian cancer samples.

Fine-tuning plant valuable secondary metabolite biosynthesis via small RNA manipulation: strategies and potential.

Plants produce secondary metabolites that serve various functions, including defense against biotic and abiotic stimuli. Many of these secondary metabolites possess valuable applications in diverse fields, including medicine, cosmetic, agriculture, and food and beverage industries, exhibiting their importance in both plant biology and various human needs. Small RNAs (sRNA), such as microRNA (miRNA) and small interfering RNA (siRNA), have been shown to play significant roles in regulating the metabolic pathways post-transcriptionally by targeting specific key genes and transcription factors, thus offering a promising tool for enhancing plant secondary metabolite biosynthesis. In this review, we summarize current approaches for manipulating sRNAs to regulate secondary metabolite biosynthesis in plants. We provide an overview of the latest research strategies for sRNA manipulation across diverse plant species, including the identification of potential sRNAs involved in secondary metabolite biosynthesis in non-model plants. We also highlight the potential future research directions, focusing on the manipulation of sRNAs to produce high-value compounds with applications in pharmaceuticals, nutraceuticals, agriculture, cosmetics, and other industries. By exploring these advanced techniques, we aim to unlock new potentials for biotechnological applications, contributing to the production of high-value plant-derived products.

A cross-sectional study comparing the expression of DNA repair molecules in subjects with and without atherosclerotic plaques.

BACKGROUND: Atherosclerosis, serving as the primary pathological mechanism at the core of cardiovascular disease, is now widely acknowledged to be associated with DNA damage and repair, contributing to atherosclerotic plaque formation. Therefore, molecules involved in the DNA repair process may play an important role in the progression of atherosclerosis. Our research endeavors to explore the contributions of specific and interrelated molecules involved in DNA repair (APE1, BRCA1, ERCC2, miR-221-3p, miR-145-5p, and miR-155-5p) to the development of atherosclerotic plaque and their interactions with each other. METHODS & RESULTS: Gene expression study was conducted using the real-time polymerase chain reaction (qRT-PCR) method on samples from carotid artery atherosclerotic plaques and nonatherosclerotic internal mammary arteries obtained from 50 patients diagnosed with coronary artery disease and carotid artery disease. Additionally, 50 healthy controls were included for the determination of 8-hydroxy-2'-deoxyguanosine (8-OHdG). Although no difference was observed in mRNA gene expressions, we noted a decrease in miR-155-5p gene expression (p = 0.003) and an increase in miR-221-3p gene expression (p = 0.015) in plaque samples, while miR-145-5p gene expression remained unchanged (p = 0.57). Regarding serum 8-OHdG levels, patients exhibited significantly higher levels (1111.82 ± 28.64) compared to controls (636.23 ± 24.23) (p < 0.0001). CONCLUSIONS: In our study demonstrating the role of miR-155-5p and miR-221-3p in atherosclerosis, we propose that these molecules are potential biomarkers and therapeutic targets for coronary artery diseases and carotid artery disease.

Overexpression of miRNA29a gene inhibits proliferation and promotes apoptosis of jejunal epithelial cells in yak.

MicroRNAs (miRNAs) were identified to be involved in various biological functions by regulating the degradation or suppressing the translation of their downstream target genes. Recent studies have identified miR-29a play a key role in functions of mammal cell differentiation, proliferation, apoptosis, and signal transduction. However, the underlying functions for miR-29a in jejunal epithelial cells biological function still to be investigated. In order to explore the yak jejunal epithelial cells proliferation and barrier dysfunction with over expression of miR-29a gene, three 0-day-old Pamir male yaks were randomly selected and slaughtered in present study, and the jejunal epithelial cells were isolated and cultured to determine yak jejunal epithelial cells proliferation and protein composition on differential expression of miR-29a gene in Pamir plateau. Here, we demonstrated that the overexpression of miR-29a gene could inhibit the proliferation of Pamir yaks jejunum epithelial cells, and contribute to the apoptosis of Pamir yaks jejunal epithelial cells with some extent. A total of 133 differentially expressed proteins were identified in different expression of miR-29a groups by label-free Mass Spectrometry (MS), which could be concluded to two predominant themes: cell proliferation and inflammatory response. Interestingly, GPR41, as a bridge protein, was contacted two predominant themes to involved in Pamir Yaks jejunal mechanical barrier PPI network, and the target proteins displayed strong mutual interactions in the complex PPI network. Overall, our study suggested that the over-expression miR-29a inhibited the jejunal epithelial cells proliferation and the expressions of specific proteins, which damaged jejunal barrier function to slow down the intestine structure and function advanced mature development during young livestock period for influence the enhanced performance of production efficiency.

Modulatory effects of miRNAs in doxorubicin resistance: A mechanistic view.

MicroRNAs (miRNAs) are a group of small non-coding RNAs and play an important role in controlling vital biological processes, including cell cycle control, apoptosis, metabolism, and development and differentiation, which lead to various diseases such as neurological, metabolic disorders, and cancer. Chemotherapy consider as gold treatment approaches for cancer patients. However, chemotherapeutic is one of the main challenges in cancer management. Doxorubicin (DOX) is an anti-cancer drug that interferes with the growth and spread of cancer cells. DOX is used to treat various types of cancer, including breast, nervous tissue, bladder, stomach, ovary, thyroid, lung, bone, muscle, joint and soft tissue cancers. Also recently, miRNAs have been identified as master regulators of specific genes responsible for the mechanisms that initiate chemical resistance. miRNAs have a regulatory effect on chemotherapy resistance through the regulation of apoptosis process. Also, the effect of miRNAs p53 gene as a key tumor suppressor was confirmed via studies. miRNAs can affect main biological pathways include PI3K pathway. This review aimed to present the current understanding of the mechanisms and effects of miRNAs on apoptosis, p53 and PTEN/PI3K/Akt signaling pathway related to DOX resistance.

Circular RNA RRM2 alleviates metabolic dysfunction-associated steatotic liver disease by targeting miR-142-5p to increase NRG1 expression.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent chronic liver condition worldwide, demanding further investigation into its pathogenesis. Circular RNAs (circRNAs) are emerging as pivotal regulators in MASLD processes, yet their pathological implications in MASLD remain poorly understood. This study focused on elucidating the role of circular RNA ribonucleotide reductase subunit M2 (circRRM2) in MASLD progression. In this study, we used both in vitro and in vivo MASLD models using long-chain-free fatty acid (FFA)-treated hepatocytes and high-fat diet (HFD)-induced MASLD in mice, respectively. We determined the expression patterns of circRRM2, microRNA-142-5p (miR-142-5p), and neuregulin 1 (NRG1) in livers of MASLD-afflicted mice and MASLD hepatocytes by RT-qPCR. Dual-luciferase reporter assays verified the binding relationships among circRRM2, miR-142-5p, and NRG1. We conducted further analyses of their roles in MASLD hepatocytes and modulated circRRM2, miR-142-5p, and NRG1 expression in vitro by transfection. Our findings were validated in vivo. The results demonstrated reduced levels of circRRM2 and NRG1, along with elevated miR-142-5p expression in MASLD livers and hepatocytes. Overexpression of circRRM2 downregulated lipogenesis-related genes and decreased triglycerides accumulation in livers of MASLD mice. MiR-142-5p, which interacts with circRRM2, effectively counteracted the effects of circRRM2 in MASLD hepatocytes. Furthermore, NRG1 was identified as a miR-142-5p target, and its overexpression mitigated the regulatory impact of miR-142-5p on MASLD hepatocytes. In conclusion, circRRM2, via its role as a miR-142-5p sponge, upregulating NRG1, possibly influenced triglycerides accumulation in both in vitro and in vivo MASLD models.NEW & NOTEWORTHY CircRRM2 expression was downregulated in free fatty acid (FFA)-challenged hepatocytes and high-fat diet (HFD) fed mice. Overexpressed circular RNA ribonucleotide reductase subunit M2 (circRRM2) attenuated metabolic dysfunction-associated steatotic liver disease (MASLD) development by suppressing FFA-induced triglycerides accumulation. CircRRM2 targeted microRNA-142-5p (miR-142-5p), which served as an upstream inhibitor of neuregulin 1 (NRG1) and collaboratively regulated MASLD progression.

MicroRNA-411-5p alleviates lipid deposition in metabolic dysfunction-associated steatotic liver disease by targeting the EIF4G2/FOXO3 axis.

BACKGROUND: Abnormal lipid deposition is an important driver of the progression of metabolic dysfunction-associated steatotic liver disease (MASLD). MicroRNA-411-5p (miR-411-5p) and eukaryotic translation initiation factor 4γ2 (EIF4G2) are related to abnormal lipid deposition, but the specific mechanism is unknown. METHODS: A high-fat, high-cholesterol diet (HFHCD) and a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) and a high-fructose diet (HFrD) were used to establish MASLD rat and mouse models, respectively. MiR-411-5p agomir and mimic were used to upregulate the miR-411-5p in vivo and in vitro, respectively. Adeno-associated virus type 8 (AAV8) carrying EIF4G2 short hairpin RNA (shRNA) and small interfering RNA (siRNA) were used to downregulate the EIF4G2 expression in vivo and in vitro, respectively. Liver histopathological analysis, Biochemical analysis and other experiments were used to explore the functions of miR-411-5p and EIF4G2. RESULTS: MiR-411-5p was decreased in both MASLD rats and mice, and was negatively correlated with liver triglycerides and serum alanine transaminase (ALT) and aspartate transaminase (AST) levels. Upregulation of miR-411-5p alleviated liver lipid deposition and hepatocellular steatosis. Moreover, miR-411-5p targeted and downregulated EIF4G2. Downregulation of EIF4G2 not only reduced liver triglycerides and serum ALT and AST levels in MASLD model, but also alleviated lipid deposition. Notably, upregulation of miR-411-5p and downregulation of EIF4G2 led to the reduction of forkhead box class O3 (FOXO3) and inhibited the expression of sterol regulatory-element binding protein 1 (SREBP1), acetyl-CoA carboxylase 1 (ACC1) and fatty acid synthase (FASN), thereby reducing fatty acid synthesis. CONCLUSIONS: Upregulation of miR-411-5p inhibits EIF4G2 to reduce the FOXO3 expression, thereby reducing fatty acid synthesis and alleviating abnormal lipid deposition in MASLD.

LncRNA XIST/miR-455-3p/HOXC4 axis promotes breast cancer development by activating TGF-ß/SMAD signaling pathway.

Breast cancer is the second primary cause of cancer death among women. Long non-coding RNA (lncRNA) X-inactive specific transcript (XIST) is a central regulator for X chromosome inactivation, and its abnormal expression is a primary feature of breast cancer. So far, the mechanism of XIST in breast cancer has not been fully elucidated. We attempted to illustrate the mechanism of XIST in breast cancer. The expressions of XIST, microRNA-455-3p (miR-455-3p) in breast cancer were measured using quantitative real-time PCR. The expressions of homeobox C4 (HOXC4) were assessed with immunohistochemical and Western blot. Also, the functions of XIST in breast cancer were assessed by Cell Counting Kit-8 analysis, colony formation assay, flow cytometry, Western blot, Transwell, and cell scratch assays. Meanwhile, the mechanism of XIST in breast cancer was validated using database analysis and dual-luciferase reporter assay. Furthermore, the function of XIST in breast cancer in vivo was estimated by tumor xenograft model, immunohistochemical assay, and hematoxylin-eosin staining. XIST and HOXC4 expressions were increased, but miR-455-3p expressions were decreased in breast cancer tissues and cells. Knocking down XIST restrained breast cancer cell proliferation, invasion, migration, epithelial-mesenchymal transformation (EMT), and induced cell cycle arrest at G0/G1. Meanwhile, XIST interacted with miR-455-3p, while miR-455-3p interacted with HOXC4. XIST knockdown repressed breast cancer cell proliferation, invasion, and EMT, while miR-455-3p inhibitor or HOXC4 overexpression abolished those impacts. HOXC4 overexpression also blocked the impacts of miR-455-3p mimic on breast cancer cell malignant behavior. In vivo experimental data further indicated that XIST knockdown repressed breast cancer cell tumorigenic ability, and decreased HOXC4 and p-SMAD3 (TGF-ß/SMAD-related protein) expressions.XIST/miR-455-3p/HOXC4 facilitated breast cancer development by activating the TGF-ß/SMAD pathway.

ZFP1 is a biomarker related to poor prognosis and immunity in gastric cancer.

We aimed to determine the prognostic significance of ZFP1 in gastric cancer (GC), its role in the immune microenvironment, and its potential as a therapeutic target using data from The Cancer Genome Atlas (TCGA) database. ZFP1 overexpression was closely associated with tumour T stage and histological grade. Patients with GC and high ZFP1 expression had poor outcomes. Lower ZFP1 expression was associated with longer symptom-free intervals and disease-specific survival. Subgroup analyses of T3 and T4, N0, N1, and M0 patients showed that overall survival (OS), disease-specific survival, and progression-free interval (PFI) were worse in those with high ZFP1 expression. ZFP1 expression in GC was moderately to strongly positively correlated with the infiltration levels of effector central memory T cells and T helper cells and negatively correlated with Th17 cells and NK CD56bright cells. The lncRNA-miRNA-ZFP1 axis was predicted using a public database. CCK8, colony formation, and wound healing assays were conducted to investigate whether ZFP1 promoted the proliferation and migration of GC cells. Our study suggests that ZFP1 plays a key role in the prognosis, immune response, and progression of GC and is a significant factor in the diagnosis and treatment of this disease.

miR-495 promotes intestinal epithelial cell apoptosis through downregulation of Sphingosine-1-phosphate.

Many pathological conditions lead to defects in intestinal epithelial integrity and loss of barrier function; Sphingosine-1-phosphate (S1P) has been shown to augment intestinal barrier integrity, though the exact mechanisms are not completely understood. We have previously shown that overexpression of Sphingosine Kinase 1 (SphK1), the rate limiting enzyme for S1P synthesis, significantly increased S1P production and cell proliferation. Here we show that microRNA 495 (miR-495) upregulation led to decreased levels of SphK1 resultant from a direct effect at the SphK1 mRNA. Increasing expression of miR-495 in intestinal epithelial cells resulted in decreased proliferation and increased susceptibility to apoptosis. Transgenic expression of miR-495 inhibited mucosal growth, as well as decreased proliferation in the crypts. The intestinal villi also expressed decreased levels of barrier proteins and exaggerated damage upon exposure to cecal ligation-puncture. These results implicate miR-495 as a critical negative regulator of intestinal epithelial protection and proliferation through direct regulation of SphK1, the rate limiting enzyme critical for production of S1P.

Serum liquid biopsy for brain tumours: a scoping analysis of practicable approaches in low- and middle-income countries.

Approaches to brain tumour diagnosis and detecting recurrence after treatment are costly and significantly invasive. Developing peripheral-sample liquid biopsy tools is the key to enhancing our ability to prognosticate brain tumour subtypes and molecular heterogeneity. The present scoping review was designed to discuss current updates in liquid biopsy tools for diagnosis and guiding clinical management of brain tumours; we evaluated the literature within the context of low-and-middle-income country challenges. Circulating tumour cells (CTCs), circulating tumour DNA (ctDNA), cell-free DNA (cfDNA), extracellular vesicle-associated biomarkers, protein biomarkers, microRNAs, and serum metabolites are discussed with the collation of current data supporting their utility in liquid biopsy. Further challenges to implanting liquid biopsy tools at a systematic level are highlighted.

Effect of whole-process high-quality nursing on the quality of life of acute pancreatitis patients and the mechanism of miR-126-5p/HOXC8 axis promoting the progression of acute pancreatitis.

The current research was designed to investigate the impact of whole-process high-quality nursing on acute pancreatitis (AP) patients' quality of life as well as the mechanism of miR-126-5p/HOXC8 axis promoting AP progression. One hundred AP patients admitted to our hospital were chosen and separated into control group (CG, n=50) and study group (SG, n=50). The CG took the routine nursing, while the SG adopted the whole-process high-quality nursing. Besides, cerulein (CE) was treated in AR42J cells to establish an experimental model of AP. The proliferation, apoptosis along with inflammation of CE-treated AR42J cells were assessed. The outcomes manifested that in contrast to the CG, the recovery time of bowel sound, the improvement time of abdominal distension, the improvement time of abdominal pain, the exhaust time and the defecation time in the SG presented shorter, the anxiety and depression scores in the SG presented lower, the WHOQOL-100 scores of patients in the SG presented higher in the fields of physiology, psychology, environment and social relations, the total incidence of complications of the SG presented lower, and the total nursing satisfaction of the SG was better. Besides, miR-126-5p presented upregulation in CE-stimulated AR42J cells, and miR-126-5p inhibition increased the proliferation along with repressed the apoptosis and inflammation in CE-stimulated AR42J cells. Moreover, HOXC8 could be the target mRNA of miR-126-5p, and HOXC8 elevation promoted the proliferation along with repressed the apoptosis and inflammation in CE-stimulated AR42J cells. In addition, rescue assays further validated that HOXC8 silence offset the protective impact of miR-126-5p repression on AP cell damage. In conclusion, our study indicated that whole-process high-quality nursing could promote the quality of life of AP patients, and revealed that miR-126-5p inhibition relieved CE-stimulated AR42J cells injury caused by AP via targeting HOXC8. Our study might offer novel insights for AP treatment and nursing.

Diagnostic value of microRNA-200 expression in peripheral blood-derived extracellular vesicles in early-stage non-small cell lung cancer.

OBJECTIVE: This study assessed the diagnostic value of microRNA-200 (miR-200) expression in peripheral blood-derived extracellular vesicles (EVs) in early-stage non-small cell lung cancer (NSCLC). METHODS: This study retrospectively analyzed 100 healthy volunteers (the control group) receiving physical examinations, 168 early-stage NSCLC patients (the NSCLC group), and 128 patients with benign lung nodules (the benign group). The basic and clinical data of participants were obtained, including age, sex, smoking history, carbohydrate antigen 242 (CA242), carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199), forced expiratory volume in 1 s, maximal voluntary ventilation, forced vital capacity, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and miR-200 expression. The correlation of miR-200 expression in peripheral blood-derived EVs with CA242, CEA, and CA199 was analyzed, and the diagnostic value of peripheral blood-derived EV miR-200 for early-stage NSCLC was assessed. The risk factors of early-stage NSCLC development were also determined. RESULTS: Age, the percentage of patients with smoking history, CA242, CEA, CA199, IL-6, and TNF-α levels, and miR-200 expression in peripheral blood-derived EVs were significantly higher in the NSCLC group than in the benign and control groups. Lung disease patients with high miR-200 expression in peripheral blood-derived EVs comprised a higher percentage of patients with smoking history and mixed lesions and had higher CA242, CEA, CA199, and TNF-α levels than those with low miR-200 expression in peripheral blood-derived EVs. In lung diseases, miR-200 expression in peripheral blood-derived EVs was significantly and positively correlated with CA242, CEA, and CA199. Peripheral blood-derived EV miR-200 combined with CA242, CEA and CA199 had higher diagnostic value (area under the curve = 0.942) than single detection, along with higher specificity, and high expression of peripheral blood-derived EV miR-200 was an independent risk factor for early-stage NSCLC. CONCLUSION: Peripheral blood-derived EV miR-200 expression in patients with lung diseases is closely correlated with CA242, CEA, and CA199, and high expression of peripheral blood-derived EV miR-200 is an independent risk factor for early-stage NSCLC and is of high clinical diagnostic value for early-stage NSCLC.

Paclitaxel hyperthermia suppresses gastric cancer migration through MiR-183-5p/PPP2CA/AKT/GSK3ß/ß-catenin axis.

BACKGROUND: Gastric cancer (GC), a prevalent malignant tumor which is a leading cause of death from malignancy around the world. Peritoneal metastasis accounts for the major cause of mortality in patients with GC. Despite hyperthermia intraperitoneal chemotherapy (HIPEC) improves the therapeutic effect of GC, it's equivocal about the mechanism under HIPEC. METHODS: MiR-183-5p expression was sifted from miRNA chip and detected in both GC patients and cell lines by qRT-PCR. Gene interference and rescue experiments were performed to identified biological function in vitro and vivo. Next, we affirmed PPP2CA as targeted of miR-183-5p by dual luciferase reporter assay. Finally, the potential relationship between HIPEC and miR-183-5p was explored. RESULTS: MiR-183-5p is up-regulated in GC and associated with advanced stage and poor prognosis. MiR-183-5p accelerate GC migration in vitro which is influenced by miR-183-5p/PPP2CA/AKT/GSK3ß/ß-catenin Axis. HIPEC exerts migration inhibition via attenuating miR-183-5p expression. CONCLUSION: MiR-183-5p can be used as a potential HIPEC biomarker in patients with CC.

Swimming alleviates myocardial fibrosis of type II diabetic rats through activating miR-34a-mediated SIRT1/PGC-1α/FNDC5 signal pathway.

Myocardial fibrosis can trigger heart failure in diabetic cardiomyopathy (DCM), and irisin, an exercise-induced myokine, may have a beneficial effect on cardiac function. However, the specific molecular mechanism between exercise and irisin in the diabetic heart remains not fully explored. This study aimed to investigate how miR-34a mediates exercise-induced irisin to ameliorate myocardial fibrosis and its underlying mechanisms. Type 2 diabetes mellitus (T2DM) with DCM was induced in adult male rats with high-fat diet and streptozotocin injection. The DCM rats were subjected to swimming (60 min/d) and recombinant irisin (r-irisin, 500 µg/kg/d) interventions for 8 weeks, respectively. Cardiac function, cardiomyocyte structure, myocardial fibrosis and its correlated gene and protein expression were analyzed. Swimming intervention alleviated insulin resistance, myocardial fibrosis, and myocardial hypertrophy, and promoted blood glucose homeostasis in T2DM model rats. This improvement was associated with irisin upregulation and miR-34a downregulation in the myocardium, thus enhancing cardiac function. Similar efficacy was observed via intraperitoneal injection of exogenous recombinant irisin. Inhibition of miR-34a in vivo exhibited an anti-myocardial fibrotic effect by promoting irisin secretion through activating sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α)/fibronectin type III domain-containing protein 5 (FNDC5) signal pathway and downregulating myocardial fibrosis markers (collagen I, collagen III, and transforming growth factor-ß1). Therefore, swimming-induced irisin has the potential therapeutic effect on diabetic myocardial fibrosis through activating the miR-34a-mediated SIRT1/PGC-1α/FNDC5 signal pathway.

The identification of key molecules and pathways in the crosstalk of calcium oxalate-treated TCMK-1 cells and macrophage via exosomes.

The interplay between crystals and epithelial cells forms the cornerstone of kidney stone development, communication between epithelial cells and macrophages emerging as a pivotal role in this process. We conducted next-generation sequencing on the secreted exosomes of TCMK-1 cells treated with calcium oxalate monohydrate (OX_EXO) or controls (NC_EXO), and on the macrophage cell line RAW264.7 stimulated with OX_EXO or NC_EXO, followed by validation of differentially expressed target proteins and miRNAs through Western blot and PCR. UPSET plots were employed to identify genes co-targeted by exosomal miRNAs. Various bioinformatic analyses were employed to predict potential mechanisms of the dysregulated genes. We integrated sequencing data from the GEO database, and validated findings using clinical patient urine and kidney tissues. We identified 665 differentially expressed exosomal miRNAs between OX_EXO and NC_EXO. Among the top 10 down-regulated miRNAs, the most targeted genes were AAK1 and NUFIP2, whereas PLCB1 was significantly targeted among the top 10 up-regulated miRNAs. In clinical specimens, we confirmed the differential expressions of five homologous miRNAs, as well as CNOT3, CNCNA1C, APEX1, and TMEM199. In conclusion, treatment of TCMK-1 cells with calcium oxalate significantly alerted the expression profile of exosomal miRNAs, subsequently influencing gene expression in macrophages, thereby modulating the processes of kidney stone formation.