The small Extracellular vesicles (sEV) has been recognized to be significant for intercellular communication due to their ability to transfer important cellular cargoes like miRNAs through circulation. The pituitary gland has not been clearly known about the role of its secreted sEV under normal physiological conditions. And Liver disease is a global public health burden. The present study is the first to investigate the effect of pituitary sEV on the liver. Sequencing and qRT-PCR revealed miR-143-3p is one of the richest in the pituitary sEV. MiR-143 Knockout (KO) mice resulted in a remarkable decrease in insulin-like growth factor 1 (IGF-1) levels and a significant increase in insulin-like growth factor binding protein 5 (IGFBP5) levels along with a reduction in liver primary cell growth. More importantly, compared with miR-143-KO-sEV, WT-sEV possesses a more robust capacity to improve miR-143 KO mice liver repair through the Wnt/β-catenin pathway after an acute injury caused by carbon tetrachloride (CCl4). Our results indicate that pituitary-derived sEV promotes hepatocyte proliferation and liver repair by its cargo miR-143-3p and provides new insight into the regulation mechanism of the pituitary-liver axis, and open a new window for endocrine regulation by using sEV.

We aimed to determine whether monitoring tumor-derived exosomal microRNAs (miRNAs) could be used to assess radiotherapeutic sensitivity in patients with locally advanced esophageal squamous cell carcinoma (ESCC). RNA sequencing was employed to conduct a comparative analysis of miRNA expression levels during radiotherapy, focusing on identifying miRNAs associated with progression. Electron microscopy confirmed the existence of exosomes, and co-cultivation assays and immunofluorescence validated their capacity to infiltrate macrophages. To determine the mechanism by which exosomal miR-143-3p regulates the interplay between ESCC cells and M2 macrophages, ESCC cell-derived exosomes were co-cultured with macrophages. Serum miR-143-3p and miR-223-3p were elevated during radiotherapy, suggesting resistance to radiation and an unfavorable prognosis for ESCC. Increased levels of both miRNAs independently predicted shorter progression-free survival (p = 0.015). We developed a diagnostic model for ESCC using serum microRNAs, resulting in an area under the curve of 0.751. Radiotherapy enhanced the release of miR-143-3p from ESCC cell-derived exosomes. Immune cell infiltration analysis at the Cancer Genome Atlas (TCGA) database revealed that ESCC cell-derived miR-143-3p triggered M2 macrophage polarization. Mechanistically, miR-143-3p upregulation affected chemokine activity and cytokine signaling pathways. Furthermore, ESCC cell exosomal miR-143-3p could be transferred to macrophages, thereby promoting their polarization. Serum miR-143-3p and miR-223-3p could represent diagnostic and prognostic markers for patients with ESCC undergoing radiotherapy. Unfavorable prognosis could be linked to the increased levels of ESCC cell-derived exosomal miR-143-3p, which might promote tumor progression by interacting with macrophages.

BACKGROUND: Circular RNAs (circRNAs), an extremely stable group of RNAs, possess a covalent closed-loop configuration. Numerous studies have highlighted the involvement of circRNAs in physiological processes and the development of various diseases. The present study aimed to investigate how circRNA regulates the osteogenic differentiation of human dental pulp stem cells (hDPSCs).
METHODS: We isolated hDPSCs from dental pulp and used next-generation sequencing analysis to determine the differentially-expressed circRNAs during osteogenic differentiation. Bioinformatics and dual-luciferase reporter assays identified the downstream targets. The role of circRNAs in osteogenic differentiation was further confirmed through the use of heterotopic bone models.
RESULTS: We found that hsa_circ_0036872 expression was increased during osteogenic differentiation of hDPSCs, and downregulation of hsa_circ_0036872 inhibited their osteogenic differentiation. Dual-luciferase reporter assays showed that both miR-143-3p and IGF2 were downstream targets of hsa_circ_0036872. Overexpression of IGF2 or inhibition of miR-143-3p restored the osteogenic differentiation ability of hDPSCs after silencing hsa_circ_0036872. Overexpression of IGF2 reversed the inhibitory effect of miR-143-3p on osteogenic differentiation.
CONCLUSIONS: Taken together, our results show that hsa_circ_0036872 exerts an important promotional effect in enhancing the osteogenesis of dental pulp stem cells by regulating the miR-143-3p/IGF2 axis. These data suggest a novel therapeutic strategy for osteoporosis treatment and periodontal tissue regeneration.

Due to the increasing trend of delayed childbirth, the age-related decline in male reproductive function has become a widely recognized issue. Sertoli cells (SCs) play a vital role in creating the necessary microenvironment for spermatogenesis in the testis. However, the mechanism underlying Sertoli cell aging is still unclear. In this study, senescent Sertoli cells showed a substantial upregulation of miR-143-3p expression. miR-143-3p was found to limit Sertoli cell proliferation, promote cellular senescence, and cause blood-testis barrier (BTB) dysfunction by targeting ubiquitin-conjugating enzyme E2 E3 (UBE2E3). Additionally, the TGF-β receptor inhibitor SB431542 showed potential in alleviating age-related BTB dysfunction, rescuing testicular atrophy, and reversing the reduction in germ cell numbers by negatively regulating miR-143-3p. These findings clarified the regulatory pathways underlying Sertoli cell senescence and suggested a promising therapeutic approach to restore BTB function, alleviate Sertoli cell senescence, and improve reproductive outcomes for individuals facing fertility challenges.

Clear cell renal cell carcinoma (ccRCC) is identified as a malignant tumor in the urinary tract. The research was an attempt to probe the biological function and molecular mechanism of lncRNA LINC00667 in ccRCC development.
qRT-PCR monitored LINC00667, miR-143-3p, and ZEB1 levels. The models of LINC00667, miR-143-3p, and ZEB1 overexpression or knockdown were constructed in ccRCC cells. Cell proliferation, apoptosis, migration, and invasion of the cells were detected. The levels of apoptosis-associated proteins and epithelial-mesenchymal transition (EMT)-related proteins, and ZEB1 were detected by WB. Dual-luciferase reporter assay and RNA pull-down assay identified the binding association between LINC00667 and miR-143-3p, miR-143-3p and ZEB1. Moreover, a xenograft tumor model in nude mice was used for evaluating tumor growth in vivo.
LINC00667 and ZEB1 displayed high expression in ccRCC tissues and cells. miR-143-3p was lowly expressed in ccRCC tissues and cells. LINC00667 targeted and repressed miR-143-3p, which inhibited ZEB1 expression in a targeted manner. Overexpression of LINC00667 facilitated ccRCC cell proliferation, migration, invasion and EMT and retarded apoptosis, whereas LINC00667 knockdown or miR-143-3p overexpression exerted reverse effects. The rescue experiments indicated that overexpressing miR-143-3p dampened LINC00667-mediated oncogenic effects. Overexpressing ZEB1 diminished miR-143-3p-mediated tumor-suppressive effects. In-vivo experiments displayed that overexpression of LINC00667 contributed to the tumor growth of ccRCC cells, in contrast to miR-143-3p overexpression, which restrained the tumor growth.
LINC00667 is up-regulated in ccRCC and enhances the ZEB1 expression by targeting miR-143-3p, which in turn accelerates ccRCC progression and induces chemoresistance.

OBJECTIVE: Insulin resistance is a key hallmark in type 2 diabetes. In recent decades, there have been numerous studies of the causes of insulin resistance. microRNAs (miRNAs) participate in the regulation of multiple aspects of energy metabolism and miR-143-3p has been shown to induce insulin resistance. We aimed to predict the downstream targets of miR-143-3p and found a miR-143-3p binding site on the 3\'-untranslated region of FNDC5 (Fibronectin type III domain containing 5) mRNA.
METHODS: We first confirmed that FNDC5 mRNA is a target of miR-143-3p using a double luciferase experiment, then constructed a prokaryotic expression system for the mature form of FNDC5, irisin, and expressed and purified irisin protein. We transfected a miR-143-3p mimic into HepG2-NTCP (Na+-taurocholate cotransporting polypeptide) cells using an NTCP targeting vector, then 24 h later, the glucose concentration of the culture medium, western blot analysis was analyzed. We next co-incubated the cells transfected with the miR-143-3p mimic with irisin for 12 h following by the assay of glucose uptake and AKT phosphorylation.
RESULTS: The glucose concentration of the culture medium was higher than that associated with control miRNA-transfected cells (p < 0.01). Western blot analysis showed that the miR-143-3p mimic significantly reduced the expression of FNDC5 (p < 0.05) and the phosphorylation of AKT (Protein kinase B) (p < 0.05), implying impaired insulin signaling. which increased the glucose uptake (p < 0.0001) and AKT phosphorylation in the cells (p < 0.05).
CONCLUSIONS: We conclude that FNDC5 is a direct target of miR-143-3p and that miR-143-3p induces insulin resistance by reducing its expression.

An altered expression of miR-143-3p has been previously reported in prostate cancer where it is purported to play a tumor suppressor role. Evidence from other cancers suggests miR-143-3p acts as an inhibitor of epithelial-to-mesenchymal transition (EMT), a key biological process required for metastasis. However, in prostate cancer the interaction between miR-143-3p and EMT-associated mechanisms remains unclear. Therefore, this paper investigated the link between miR-143-3p and EMT in prostate cancer using in vitro and in silico analyses. PCR detected that miR-143-3p expression was significantly decreased in prostate cancer cell lines compared to normal prostate cells. Bioinformatic analysis of The Cancer Genome Atlas Prostate Adenocarcinoma (TCGA PRAD) data showed a significant downregulation of miR-143-3p in prostate cancer, correlating with pathological markers of advanced disease. Functional enrichment analysis confirmed the significant association of miR-143-3p and its target genes with EMT. The EMT-linked gene AKT1 was subsequently shown to be a novel target of miR-143-3p in prostate cancer cells. The in vitro manipulation of miR-143-3p levels significantly altered the cell proliferation, clonogenicity, migration and expression of EMT-associated markers. Further TCGA PRAD analysis suggested miR-143-3p tumor expression may be a useful predictor of disease recurrence. In summary, this is the first study to report that miR-143-3p overexpression in prostate cancer may inhibit EMT by targeting AKT1. The findings suggest miR-143-3p could be a useful diagnostic and prognostic biomarker for prostate cancer.

BACKGROUND: Airway epithelial cells epithelial mesenchymal transition (EMT) and lung fibroblasts extracellular matrix (ECM) production are the key steps in airway remodeling. Our previous study demonstrated that miR-143-3p has the ability to impede airway smooth muscle cell proliferation and ECM deposition. However, the function of miR-143-3p in airway epithelial cells and lung fibroblasts remains unclear.
METHODS: Cell viability was determined using MTT method, while cell migration was evaluated through scratch assay. EMT and ECM proteins were detected by western blot, RT-qPCR, and ELISA. To determine the level of miR-143-3p m6A methylation, we employed the meRIP-qPCR assay. Additionally, the binding of miR-143-3p with Smad3 were projected by bioinformatics and validated by dual luciferase reporter assays.
RESULTS: It was discovered that the expression of miR-143-3p were lower in both asthma patients and TGF-β1-treated human bronchial epithelial 16HBE cells and human lung fibroblast HPF cells. Upregulation of miR-143-3p restrained 16HBE cell migration, and decreased EMT mesenchymal markers and increased epithelial markers. And upregulation of miR-143-3p impaired cell viability and ECM protein production in HPF cells. Mechanistically, interfering with METTL3 resulted in decreased m6A modification of miR-143-3p and led to lower levels of miR-143-3p. Moreover, miR-143-3p were verified to directly target and downregulate Smad3. Upregulation of Smad3 attenuated the effects of miR-143-3p on cell EMT and ECM production.
CONCLUSIONS: MiR-143-3p inhibits airway epithelial cell EMT as well as lung fibroblast ECM production by downregulating Smad3. Therefore, miR-143-3p may be a promising target to reduce airway remodeling in asthma.

The ovary is a highly susceptible organ to senescence, and granulosa cells (GCs) have a crucial role in oocyte development promotion and overall ovarian function maintenance. As age advances, GCs apoptosis and dysfunction escalate, leading to ovarian aging. However, the molecular mechanisms underpinning ovarian aging remain poorly understood. In this study, we observed a correlation between the age-related decline of fertility and elevated expression levels of miR-143-3p in female mice. Moreover, miR-143-3p was highly expressed in senescent ovarian GCs. The overexpression of miR-143-3p in GCs not only hindered their proliferation and induced senescence-associated secretory phenotype (SASP) but also impeded steroid hormone synthesis by targeting ubiquitin-conjugating enzyme E2 E3 (Ube2e3) and luteinizing hormone and human chorionic gonadotropin receptor (Lhcgr). These findings suggest that miR-143-3p plays a substantial role in senescence and steroid hormone synthesis in GCs, indicating its potential as a therapeutic target for interventions in the ovarian aging process.

The remodeling of uterine spiral arteries is a complex process requiring the dynamic action of various cell types. During early pregnancy, extravillous trophoblast (EVT) cells differentiate and invade the vascular wall, replacing the vascular smooth muscle cells (VSMCs). Several in vitro studies have shown that EVT cells play an important role in promoting VSMC apoptosis, however, the mechanism underlying this process is not fully understood. In this study, we demonstrated that EVT-conditioned media and EVT-derived exosomes could induce VSMC apoptosis. Through data mining and experimental verification, it was demonstrated that the EVT exosome miR-143-3p induced VSMC apoptosis in both VSMCs and a chorionic plate artery (CPA) model. Furthermore, FAS ligand was also expressed on the EVT exosomes and may play a co-ordinated role in apoptosis induction. These data clearly demonstrated that VSMC apoptosis is mediated by EVT-derived exosomes and their cargo of miR-143-3p as well as their cell surface presentation of FASL. This finding increases our understanding of the molecular mechanisms underlying the regulation of VSMC apoptosis during spiral artery remodeling.