Identification of an Exosome-relevant SNHG6-hsa-miR-429- CHRDL1/CCNA2 Axis for Lung Adenocarcinoma Prognosis Evaluation.

AIM: To explore an exosome-relevant molecular classification in lung adenocarcinoma (LUAD). BACKGROUND: Exosome genes or relevant non-coding RNAs are regulators of cancer treatment and prognosis, but their function in LUAD has not yet been determined. OBJECTIVE: Unraveling a molecular classification applying exosome-related RNA networks for LUAD prognosis evaluation. METHODS: MicroRNA sequencing data (miRNAs-seq) and RNA sequencing data (RNA- seq) were derived from The Cancer Genome Atlas (TCGA). The ConsensusCluster- Plus package was used for molecular typing in LUAD based on 121 Exosome-related genes. Then, a limma package was conducted to explore differentially expressed mRNAs (DEmRNAs), differentially expressed miRNAs (DEmiRNAs) and differentially expressed lncRNAs (DElncRNAs) in molecular typing for constructing an Exosome-driven competing endogenous RNA network (ceRNA). Dominant miRNAs, as well as target mRNAs, were identified by COX modeling and Kaplan-Meier survival analysis. RESULTS: Two Exosome-associated molecular clusters classified in LUAD. The C2 cluster favored high clinicopathology and showed a trend toward poor prognosis. 29 lncRNA- miRNA and 12 miRNA-mRNA interaction pairs were identified. The hsa-miR-429 was the pivotal miRNA in the network that affected the prognosis of LUAD. According to the interaction relationship and LUAD prognostic role, SNHG6-hsa- miR-429-CHRDL1/CCNA2 was identified. SNHG6-hsa-miR-429-CHRDL1 exerts oncogenic effects, and SNHG6-hsa-miR-429- CCNA2 exerts pro-oncogenic effects. CONCLUSION: Overall, our study identified an Exosome-driven ceRNA network in LUAD, and the SNHG6-hsa-miR-429-CHRDL1/CCNA2 axis could be a new therapeutic target for LUAD and our study provides new insights into the molecular mechanisms of LUAD.

Diagnostic value of miR-200 family in non-small cell lung cancer: a meta-analysis.

Aim: To investigate the diagnostic potential of the miR-200 family for early detection in non-small cell lung cancer (NSCLC). Materials & methods: A systematic search was conducted of PubMed, Embase and Web of Science databases to identify studies of the miR-200 family in NSCLC. Sixteen studies meeting the inclusion criteria were included in the analysis with a total of 20 cohorts. Results: The combined sensitivity and specificity reached 73% and 85%, with an area under the curve of 0.83. Notably, miR-200b introduced heterogeneity. Subgroup analysis highlighted miR-200a and miR-141 as more sensitive, while blood-derived miRNAs showed slightly lower accuracy. Conclusion: The miR-200 family, predominantly assessed in blood, exhibits significant diagnostic potential for NSCLC, especially in distinguishing it from benign diseases.

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Circular RNA circLIFR suppresses papillary thyroid cancer progression by modulating the miR-429/TIMP2 axis.

PURPOSE: Circular RNAs (circRNAs) are increasingly recognized for their important roles in various cancers, including papillary thyroid cancer (PTC). The specific mechanisms by which the circLIF receptor subunit alpha (circLIFR, hsa_circ_0072309) influences PTC progression remain largely unknown. METHODS: In our study, CircLIFR, miR-429, and TIMP2 levels were assessed using reverse transcription-quantitative PCR. The roles of circLIFR and miR-429 in PTC cells were determined using Cell Counting Kit-8, colony formation, wound healing, and Transwell assays. Western blotting was utilized to examine the levels of TIMP2. The direct interaction between circLIFR, TIMP2, and miR-429 was confirmed using dual-luciferase reporter, RNA immunoprecipitation, and fluorescence in situ hybridization assays. RESULTS: In PTC tissues and cells, a decrease in circLIFR and TIMP2 levels, accompanied by an increase in miR-429 levels, was observed. Overexpression of circLIFR or downregulation of miR-429 effectively suppressed the proliferation and migration of PTC cells. Conversely, the knockdown of circLIFR or overexpression of miR-429 had the opposite effect. Furthermore, circLIFR overexpression suppressed tumor growth in vivo. Mechanistically, circLIFR modulated TIMP2 expression by serving as a sponge for miR-429. Rescue experiments indicated that the antitumor effect of circLIFR could be reversed by miR-429. CONCLUSION: This study confirmed circLIFR as a novel tumor suppressor delayed PTC progression through the miR-429/TIMP2 axis. These findings suggested that circLIFR held promise as a potential therapeutic target for PTC.

Palmitic acid reduces the methylation of the FOXO1 promoter to suppress the development of diffuse large B-cell lymphoma via modulating the miR-429/DNMT3A axis.

Diffuse large B-cell lymphoma (DLBCL) is characterized by significant treatment resistance. Palmitic acid (PA) has shown promising antitumor properties. This study aims to elucidate the molecular mechanisms by which PA influences DLBCL progression. We quantified the expression levels of microRNAs (miRNAs), Forkhead box protein O1 (FOXO1), and DNA methyltransferase 3A (DNMT3A) in both untreated and PA-treated DLBCL tumors and cell lines. Assessments were made of cell viability, apoptosis, and autophagy-related protein expression following PA administration. Interaction analyses among miR-429, DNMT3A, and FOXO1 were conducted using luciferase reporter assays and methylation-specific (MSP) Polymerase chain reaction (PCR). After transfecting the miR-429 inhibitor, negative control (NC) inhibitor, shRNA against DNMT3A (sh-DNMT3A), shRNA negative control (sh-NC), overexpression vector for DNMT3A (oe-DNMT3A), or overexpression negative control (oe-NC), we evaluated the effects of miR-429 and DNMT3A on cell viability, mortality, and autophagy-related protein expression in PA-treated DLBCL cell lines. The efficacy of PA was also tested in vivo using DLBCL tumor-bearing mouse models. MiR-429 and FOXO1 expression levels were downregulated, whereas DNMT3A was upregulated in DLBCL compared to the control group. PA treatment was associated with enhanced autophagy, mediated by the upregulation of miR-429 and downregulation of DNMT3A. The luciferase reporter assay and MSP confirmed that miR-429 directly inhibits DNMT3A, thereby reducing FOXO1 methylation. Subsequent experiments demonstrated that PA promotes autophagy and inhibits DLBCL progression by upregulating miR-429 and modulating the DNMT3A/FOXO1 axis. In vivo PA significantly reduced the growth of xenografted tumors through its regulatory impact on the miR-429/DNMT3A/FOXO1 axis. Palmitic acid may modulate autophagy and inhibit DLBCL progression by targeting the miR-429/DNMT3A/FOXO1 signaling pathway, suggesting a novel therapeutic target for DLBCL management.

Exosomes enriched by miR-429-3p derived from ITGB1 modified Telocytes alleviates hypoxia-induced pulmonary arterial hypertension through regulating Rac1 expression.

BACKGROUND: Recent studies have emphasized the critical role of Telocytes (TCs)-derived exosomes in organ tissue injury and repair. Our previous research showed a significant increase in ITGB1 within TCs. Pulmonary Arterial Hypertension (PAH) is marked by a loss of microvessel regeneration and progressive vascular remodeling. This study aims to investigate whether exosomes derived from ITGB1-modified TCs (ITGB1-Exo) could mitigate PAH. METHODS: We analyzed differentially expressed microRNAs (DEmiRs) in TCs using Affymetrix Genechip miRNA 4.0 arrays. Exosomes isolated from TC culture supernatants were verified through transmission electron microscopy and Nanoparticle Tracking Analysis. The impact of miR-429-3p-enriched exosomes (Exo-ITGB1) on hypoxia-induced pulmonary arterial smooth muscle cells (PASMCs) was evaluated using CCK-8, transwell assay, and inflammatory factor analysis. A four-week hypoxia-induced mouse model of PAH was constructed, and H&E staining, along with Immunofluorescence staining, were employed to assess PAH progression. RESULTS: Forty-five miRNAs exhibited significant differential expression in TCs following ITGB1 knockdown. Mus-miR-429-3p, significantly upregulated in ITGB1-overexpressing TCs and in ITGB1-modified TC-derived exosomes, was selected for further investigation. Exo-ITGB1 notably inhibited the migration, proliferation, and inflammation of PASMCs by targeting Rac1. Overexpressing Rac1 partly counteracted Exo-ITGB1's effects. In vivo administration of Exo-ITGB1 effectively reduced pulmonary vascular remodeling and inflammation. CONCLUSIONS: Our findings reveal that ITGB1-modified TC-derived exosomes exert anti-inflammatory effects and reverse vascular remodeling through the miR-429-3p/Rac1 axis. This provides potential therapeutic strategies for PAH treatment.

CircNSD1 promotes cardiac fibrosis through targeting the miR-429-3p/SULF1/Wnt/ß-catenin signaling pathway.

Cardiac fibrosis is a detrimental pathological process, which constitutes the key factor for adverse cardiac structural remodeling leading to heart failure and other critical conditions. Circular RNAs (circRNAs) have emerged as important regulators of various cardiovascular diseases. It is known that several circRNAs regulate gene expression and pathological processes by binding miRNAs. In this study we investigated whether a novel circRNA, named circNSD1, and miR-429-3p formed an axis that controls cardiac fibrosis. We established a mouse model of myocardial infarction (MI) for in vivo studies and a cellular model of cardiac fibrogenesis in primary cultured mouse cardiac fibroblasts treated with TGF-ß1. We showed that miR-429-3p was markedly downregulated in the cardiac fibrosis models. Through gain- and loss-of-function studies we confirmed miR-429-3p as a negative regulator of cardiac fibrosis. In searching for the upstream regulator of miR-429-3p, we identified circNSD1 that we subsequently demonstrated as an endogenous sponge of miR-429-3p. In MI mice, knockdown of circNSD1 alleviated cardiac fibrosis. Moreover, silence of human circNSD1 suppressed the proliferation and collagen production in human cardiac fibroblasts in vitro. We revealed that circNSD1 directly bound miR-429-3p, thereby upregulating SULF1 expression and activating the Wnt/ß-catenin pathway. Collectively, circNSD1 may be a novel target for the treatment of cardiac fibrosis and associated cardiac disease.

MicroRNA 429 regulates MMPs expression by modulating TIMP2 expression in colon cancer cells and inflammatory colitis.

BACKGROUND: In a previous study, we found that the expression of microRNA 429 (MIR429) was decreased in dextran sodium sulfate (DSS)-induced mouse colitis tissues. OBJECTIVE: In this study, we aimed to investigate the interaction of MIR429 with TIMP metallopeptidase inhibitor 2 (TIMP2), one of its candidate target genes, in human colorectal cancer (CRC) cells and DSS-induced mouse colitis tissues. METHODS: A luciferase reporter system was used to confirm the effect of MIR429 on TIMP2 expression. The expression levels of MIR429 and target genes in cells or tissues were evaluated through quantitative RT-PCR, western blotting, or immunohistochemistry. RESULTS: We found that the expression level of MIR429 was downregulated in human CRC tissues, and also showed that TIMP2 is a direct target gene of MIR429 in CRC cell lines. Furthermore, MIR429 regulate TIMP2-mediated matrix metallopeptidases (MMPs) expression in CRC cells. We also generated cell lines stably expressing MIR429 in CRC cell lines and showed that MIR429 regulates the expression of MMPs by mediating TIMP2 expression. In addition to human CRC tissues, we found that TIMP2 was highly expressed in mouse colitis tissues and human ulcerative colitis (UC) tissues. CONCLUSIONS: Our findings suggest that the expression of endogenous MIR429 was reduced in human CRC tissues and colitis, leading to upregulation of its target gene TIMP2. The upregulation of TIMP2 by decreased MIR429 expression in CRC tissues and inflamed tissues suggests that it may affect extracellular matrix (ECM) remodeling through downregulation of MMPs. Therefore, MIR429 may have therapeutic value for human CRC and colitis.

CRKL but not CRKII contributes to hemin-induced erythroid differentiation of CML.

Destruction of erythropoiesis process leads to various diseases, including thrombocytopenia, anaemia, and leukaemia. miR-429-CT10 regulation of kinase-like (CRKL) axis involved in development, progression and metastasis of cancers. However, the exact role of miR-429-CRKL axis in leukaemic cell differentiation are still unknown. The current work aimed to uncover the effect of miR-429-CRKL axis on erythropoiesis. In the present study, CRKL upregulation was negatively correlated with miR-429 downregulation in both chronic myeloid leukaemia (CML) patient and CR patient samples. Moreover, CRKL expression level was significantly decreased while miR-429 expression level was increased during the erythroid differentiation of K562 cells following hemin treatment. Functional investigations revealed that overexpression and knockdown of CRKL was remarkably effective in suppressing and promoting hemin-induced erythroid differentiation of K562 cells, whereas, miR-429 exhibited opposite effects to CRKL. Mechanistically, miR-429 regulates erythroid differentiation of K562 cells by downregulating CRKL via selectively targeting CRKL-3'-untranslated region (UTR) through Raf/MEK/ERK pathway. Conversely, CRKII had no effect on erythroid differentiation of K562 cells. Taken together, our data demonstrated that CRKL (but not CRKII) and miR-429 contribute to development, progression and erythropoiesis of CML, miR-429-CRKL axis regulates erythropoiesis of K562 cells via Raf/MEK/ERK pathway, providing novel insights into effective diagnosis and therapy for CML patients.

miR-429-3p mediates memory decline by targeting MKP-1 to reduce surface GluA1-containing AMPA receptors in a mouse model of Alzheimer's disease.

Alzheimer's disease (AD) is a leading cause of dementia in the elderly. Mitogen-activated protein kinase phosphatase 1 (MKP-1) plays a neuroprotective role in AD. However, the molecular mechanisms underlying the effects of MKP-1 on AD have not been extensively studied. MicroRNAs (miRNAs) regulate gene expression at the post-transcriptional level, thereby repressing mRNA translation. Here, we reported that the microRNA-429-3p (miR-429-3p) was significantly increased in the brain of APP23/PS45 AD model mice and N2AAPP AD model cells. We further found that miR-429-3p could downregulate MKP-1 expression by directly binding to its 3'-untranslated region (3' UTR). Inhibition of miR-429-3p by its antagomir (A-miR-429) restored the expression of MKP-1 to a control level and consequently reduced the amyloidogenic processing of APP and Aß accumulation. More importantly, intranasal administration of A-miR-429 successfully ameliorated the deficits of hippocampal CA1 long-term potentiation and spatial learning and memory in AD model mice by suppressing extracellular signal-regulated kinase (ERK1/2)-mediated GluA1 hyperphosphorylation at Ser831 site, thereby increasing the surface expression of GluA1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). Together, these results demonstrate that inhibiting miR-429-3p to upregulate MKP-1 effectively improves cognitive and synaptic functions in AD model mice, suggesting that miR-429/MKP-1 pathway may be a novel therapeutic target for AD treatment.

RUNX1/miR-429 feedback loop promotes growth, metastasis, and epithelial-mesenchymal transition in oral squamous cell carcinoma by targeting ITGB1.

This study aimed to explore the role of miR-429 on the progression of oral squamous cell carcinoma (OSCC). OSCC cell lines were transfected with miR-429 mimic, pcDNA3.1-RUNX1, or pcDNA3.1-ITGB1, and their cell viability, apoptosis, migration, and invasion abilities were analyzed by cell counting, terminal deoxynucleotidyl transferase dUTP nick-end labeling staining, wound healing, and transwell assays, respectively. Furthermore, luciferase reporter assay, RNA pull-down, and ChIP were used to assess the regulation of miR-429, RUNX1, and ITGB1 expression in OSCC. Lastly, the biological role of the RUNX1/miR-429 feedback loop was explored in nude mice. The results revealed that miR-429 level was down-regulated, while RUNX1 and ITGB1 levels were up-regulated in OSCC tissues and that miR-429 was negatively correlated with RUNX1 and ITGB1 in OSCC tissues. Transfection of miR-429 mimic suppressed OSCC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). Moreover, we found that miR-429 participated in OSCC progression by directly targeting ITGB1. Additionally, we found that RUNX1 negatively regulated miR-429 expression by binding to its promoter. Our results also revealed that the RUNX1/miR-429 feedback loop regulated ITGB1 expression and that RUNX1 overexpression rescued the inhibitory effects of miR-429 mimic on OSCC cells. In addition, miR-429 mimic significantly suppressed tumor growth, inflammatory cell infiltration, EMT, and ITGB1 expression in vivo, which were inhibited by RUNX1 overexpression. Altogether, these results indicate that the RUNX1/miR-429 feedback loop promoted growth, metastasis, and EMT in OSCC by targeting ITGB1.

Profiling of Serum miRNAs Constructs a Diagnostic 3-miRNA Panel for Clear-Cell Renal Cell Carcinoma.

BACKGROUND: Renal cell carcinoma (RCC) carries significant morbidity and mortality globally with an increasing incidence per year predominantly represented by clear-cell renal cell carcinoma (ccRCC) which accounts for 70-80% of all RCC cases. MicroRNAs(miRNAs) implicate tumor development and progression in epigenetic mechanisms and available profiling of serum miRNAs potentiate them as diagnostic markers for various cancers. MATERIALS AND METHODS: A total of 108 ccRCC patients and 112 normal controls were enrolled. A 3-stage experiment was conducted to identify differentially expressed serum miRNAs in ccRCC and establish a diagnostic miRNAs panel. Additionally, bioinformatic analysis was employed to predict selected miRNAs' target genes, preform functional annotation and explore the roles in ccRCC. RESULTS: MiR-429, miR-10a-5p, miR-154-5p were found to be up-regulated miRNAs. Inversely, miR-27a-3p and miR-221-3p were found to be down-regulated miRNAs. These 5 miRNAs were selected to construct diagnostic panel by backward stepwise logistic regression analysis and ultimately a 3-miRNA panel (miR-429, miR-10a-5p and miR-27a-3p) was established [area under the curve (AUC) = 0.897, sensitivity = 85.0%, specificity = 83.3%]. CONCLUSION: The panel of 3-miRNA holds promise as a novel, convenient, and noninvasive diagnostic method for early detection of ccRCC.

Ssc-miR-429 expression proliles and functions on inducing Leydig cells apoptosis.

Leydig cells (LCs) play an indispensable role in testosterone synthesis, and their dysfunction can result in male reproductive disorders. Previous transcriptome sequencing revealed differential expression of MicroRNA-429 (miR-429) in both Leydig stem cells (SLCs) and LCs, indicating its potential regulatory function in LCs. In this study, we examined the expression of miR-429 in seven pig tissues (heart, liver, spleen, lung, kidney, testis, epididymis, brain) and investigated its impact on the proliferation and apoptosis of testicular interstitial cells using various techniques such as CCK-8, EdU, TUNEL, Western blot, among others. The results demonstrated that miR-429 exhibited lower expression levels in the testis, particularly in the LCs of testicular tissue. Upon upregulation of miR-429, TM3 cell density significantly increased, while downregulation led to a slight elevation in cell density. Further research indicated that the observed phenotype was due to miR-429-induced cell apoptosis, independent of cell proliferation. Additionally, a dual-luciferase reporter system revealed no targeting relationship between miR-429 and the predicted target genes (BMI1 and SOX5). Previous reports confirm Bcl2 as a known target of miR-429, leading us to hypothesize that miR-429 diminishes LCs' anti-apoptotic capability by inhibiting Bcl2. In summary, our findings suggest that miR-429 may induce LC apoptosis, supporting its potential as a biomarker for male reproductive disorders linked to Leydig cell dysfunction.

miR-429-3p mediates memory decline by targeting MKP-1 to reduce surface GluA1-containing AMPA receptors in a mouse model of Alzheimer's disease

Alzheimer's disease (AD) is a leading cause of dementia in the elderly. Mitogen-activated protein kinase phosphatase 1 (MKP-1) plays a neuroprotective role in AD. However, the molecular mechanisms underlying the effects of MKP-1 on AD have not been extensively studied. MicroRNAs (miRNAs) regulate gene expression at the post-transcriptional level, thereby repressing mRNA translation. Here, we reported that the microRNA-429-3p (miR-429-3p) was significantly increased in the brain of APP23/PS45 AD model mice and N2AAPP AD model cells. We further found that miR-429-3p could downregulate MKP-1 expression by directly binding to its 3'-untranslated region (3' UTR). Inhibition of miR-429-3p by its antagomir (A-miR-429) restored the expression of MKP-1 to a control level and consequently reduced the amyloidogenic processing of APP and Aβ accumulation. More importantly, intranasal administration of A-miR-429 successfully ameliorated the deficits of hippocampal CA1 long-term potentiation and spatial learning and memory in AD model mice by suppressing extracellular signal-regulated kinase (ERK1/2)-mediated GluA1 hyperphosphorylation at Ser831 site, thereby increasing the surface expression of GluA1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). Together, these results demonstrate that inhibiting miR-429-3p to upregulate MKP-1 effectively improves cognitive and synaptic functions in AD model mice, suggesting that miR-429/MKP-1 pathway may be a novel therapeutic target for AD treatment.

Circ_0003789 Knockdown Inhibits Tumor Progression by miR-429/ZFP36L2 Axis in Gastric Cancer.

An increasing number of circRNAs have been found to be involved in the development of gastric cancer. However, the function of circ_0003789 in regulating gastric cancer progression is unclear. Here, we aimed to investigate the expression, function and molecular mechanism of circ_0003789 in gastric cancer pathogenesis. Circ_0003789, miR-429 and ZFP36 ring finger protein like 2 (ZFP36L2) mRNA were quantified by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was illustrated by 5-Ethynyl-2'-deoxyuridine (Edu), cell counting kit-8 (CCK-8) and colony formation assays. Apoptosis was determined by flow cytometry. Protein level was detected by Western blotting assay. Xenograft assays were used for functional analysis of circ_0003789 in vivo. The relationship between miR-429 and circ_0003789 or ZFP36L2 was predicted by starbase3.0 online database and identified by dual luciferase reporter assay. The expression levels of circ_0003789 and ZFP36L2 were significantly upregulated in gastric cancer tissues and cells, while the expression of miR-429 was downregulated. Downregulation of circ_0003789 inhibited gastric cancer cell growth and invasion and promoted apoptosis in vitro. Circ_0003789 acted as a sponge of miR-429. Moreover, miR-429 silencing by miR-429 inhibitors attenuated the effects of circ_0003789 interference on cell growth, apoptosis and invasion. ZFP36L2 was targeted by miR-429, and the effects of miR-429 on cell growth, invasion and apoptosis were attenuated by ZFP36L2 overexpression. Circ_0003789 could enhance ZFP36L2 expression by interacting with miR-429. Silencing of circ_0003789 inhibited tumor growth in vivo. Circ_0003789 regulates tumor progression in gastric cancer through miR-429/ZFP36L2 axis. This finding implies that circ_0003789 may be a therapeutic target for gastric cancer.

Upregulated microRNA-429 confers endometrial stromal cell dysfunction by targeting HIF1AN and regulating the HIF1A/VEGF pathway.

Endometriosis (EM) is a prevalent estrogen-dependent disorder that adversely affects the life quality of many reproductive-age women. Previous evidence has suggested the significant role of miR-429 in EM; however, its molecular mechanisms underlying EM pathogenesis are unclarified. Human endometrial stromal cells (HESCs) were identified using immunofluorescence staining and flow cytometry. A mouse EM model was established by endometrial auto-transplantation. RNA and protein expression of molecules was examined using real-time quantitative polymerase chain reaction and western blotting, respectively. In vitro functional experiments showed that inhibiting miR-429 restrained HESC proliferation, migration, and invasiveness. Luciferase reporter assay confirmed that miR-429 targeted hypoxia-inducible factor 1 subunit alpha inhibitor (HIF1AN) in HESCs. HIF1AN silencing offset the negative regulation of miR-429 inhibition on the HIF1A/vascular endothelial growth factor (VEGF) signaling pathway. In vivo experiments showed that depletion of miR-429 attenuated ectopic lesion development in the mouse EM model. Collectively, suppressing miR-429 hinders the invasive behaviors of HESCs and EM progression in mice by targeting HIF1AN and regulating the HIF1A/VEGF signaling pathway.

miR-429 Suppresses Endometrial Cancer Progression and Drug Resistance via DDX53.

(1) Background: To examine miR-429-meditated DEAD (Asp-Glu-Ala-Asp) box polypeptide 53 (DDX53) function in endometrial cancer (EC). (2) Methods: DDX53 and miR-429 levels were measured using quantitative real-time polymerase chain reaction and western blotting assays, cell invasion and migration using Transwell invasion and wound healing assays, and cell proliferation using colony-forming/proliferation assays. A murine xenograft model was also generated to examine miR-429 and DDX53 functions in vivo. (3) Results: DDX53 overexpression (OE) promoted key cancer phenotypes (proliferation, migration, and invasion) in EC, while in vivo, DDX53 OE hindered tumor growth in the murine xenograft model. Moreover, miR-429 was identified as a novel miRNA-targeting DDX53, which suppressed EC proliferation and invasion. (4) Conclusions: DDX53 and miR-429 regulatory mechanisms could provide novel molecular therapies for EC.

The oncogenic miR-429 promotes triple-negative breast cancer progression by degrading DLC1.

Lines of evidence have demonstrated that the oncogenic miRNAs are pivotal to the progression of breast cancer. In this study, we investigated the biological traits of microRNA-429 (miR-429) in triple-negative breast cancer (TNBC) and the underlying molecular mechanism. We found that miR-429 was notably overexpressed in TNBC, and promoted TNBC cell proliferation, migration, and invasion by degrading the tumor suppressor DLC1. In conclusion, our findings reveal the mechanism of tumorigenic miR-429 in TNBC, which paves the way for target therapies translation in clinical settings.

miR-429 inhibits the formation of an immunosuppressive microenvironment to counteract hepatocellular carcinoma immune escape by targeting PD-L1.

Recent advances in immunotherapeutic approaches have the potential to bring new hope to the treatment of pancreatic cancer. The tumor microenvironment contributes significantly to tumor development and progression. In this study, miR-429 overexpression was found to inhibit proliferation, invasion, and clonogenicity while promoting apoptosis in HepG2 cells. Furthermore, co-culture of miR-429-overpressing or silenced HepG2 cells with PBMCs showed that miR-429 induced CD4+ and CD8+ T cell infiltration, decreased the numbers of Tregs, inhibited CD8+ T cell apoptosis and exhaustion, and enhanced CD8+ T cell functions in PBMCs. miR-429 was found to prevent an immunosuppressive HCC microenvironment by targeting and suppressing PD-L1. In a C57BL/6 mouse subcutaneous xenograft tumor model, overexpression of miR-429 reduced tumorigenesis and both tumor volumes and weights were decreased relative to controls. In addition, CD4+ and CD8+ T cells were increased, Tregs were reduced, and CD8+ T cell apoptosis and depletion were reduced in the tumor tissues induced by miR-429-overexpressing HepG2 cells.

Circulating microRNAs for Early Diagnosis of Ovarian Cancer: A Systematic Review and Meta-Analysis.

In this study, we conducted a systematic review and meta-analysis to summarize and evaluate the global research potential of different circulating miRNAs as an early diagnostic biomarker for OC. A systematic literature search for relevant studies was conducted in June 2020 and followed up in November 2021. The search was conducted in English databases (PubMed, ScienceDirect). The primary search resulted in a total of 1887 articles, which were screened according to the prior established inclusion and exclusion criteria. We identified 44 relevant studies, of which 22 were eligible for the quantitative meta-analysis. Statistical analysis was performed using the Meta-package in Rstudio. Standardized mean differences (SMD) of relative levels between control subjects and OC patients were used to evaluate the differential expression. All studies were quality evaluated using a Newcastle-Ottawa Scale. Based on the meta-analysis, nine miRNAs were identified as dysregulated in OC patients compared to controls. Nine were upregulated in OC patients compared to controls (miR-21, -125, -141, -145, -205, -328, -200a, -200b, -200c). Furthermore, miR-26, -93, -106 and -200a were analyzed, but did not present an overall significant difference between OC patients and controls. These observations should be considered when performing future studies of circulating miRNAs in relation to OC: sufficient size of clinical cohorts, development of consensus guidelines for circulating miRNA measurements, and coverage of previously reported miRNAs.

Exosomal miR-429 derived from adipose-derived stem cells ameliorated chondral injury in osteoarthritis via autophagy by targeting FEZ2.

BACKGROUND: Osteoarthritis (OA) is the most prevalent musculoskeletal disease, imposing a significant public health burden. Exosomes might be an effective means of treating OA. PURPOSE: To investigate the role of exosomes from adipose tissue-derived stromal cells (ADSCs) in OA. We explored whether exosomes from ADSCs could be absorbed by OA chondrocytes, whether there were differences in miR-429 expression in the exosomes of ADSCs and chondrocytes, and whether ADSC exosomal miR-429 could enhance chondrocyte proliferation to exert therapeutic effects in OA. STUDY DESIGN: Controlled laboratory study. METHODS: ADSCs were isolated and cultured from 4-week-old Sprague-Dawley rats. ADSCs and chondrocytes were identified by flow cytometry assay and fluorescent staining, respectively. The exosomes were extracted and identified. Exosome transport was verified by cell staining and co-culture. Beclin 1, collagen II, LC3-II/I, miR-429, and FEZ2 mRNA and protein expression were investigated with real-time PCR and western blotting, respectively. Chondrocyte proliferation was investigated with Cell Counting Kit-8 (CCK-8) assay. The association between miR-429 and FEZ2 was verified with luciferase assay. A rat OA model was established and rat knee joint cartilage tissue was examined with hematoxylin-eosin and toluidine blue staining. RESULTS: Both ADSCs and chondrocytes secreted exosomes and ADSC-derived exosomes could be absorbed by the chondrocytes. ADCS exosomes contained higher miR-429 levels than chondrocyte exosomes. The luciferase assay demonstrated that miR-429 directly targeted FEZ2. Compared with the OA group, miR-429 promoted chondrocyte proliferation while FEZ2 decreased it. miR-429 promoted autophagy by targeting FEZ2 to ameliorate cartilage injury. In vivo, miR-429 promoted autophagy to alleviate OA by targeting FEZ2. CONCLUSION: ADSC exosomes could be beneficial for OA and could be absorbed by chondrocytes to promote chondrocyte proliferation through miR-429. miR-429 ameliorated cartilage injury in OA by targeting FEZ2 and promoting autophagy.