microRNA-141-3p Suppressed the Progression of the Clear Cell Renal Cell Carcinoma by Targeting Transforming Growth Factor Beta 2 Gene Expression.

Clear cell renal cell carcinoma (ccRCC) is a malignant tumor of kidney epithelial cells, one of the most common tumors in the world. Transforming growth factor beta (TGFß)1 is a crucial factor that induces epithelial-mesenchymal transition (EMT) in cancer cells. microRNA-141-3p (miR-141-3p) is a microRNA that is considered a tumor suppressor. However, the role and mechanism of miR-141-3p in TGFß1-induced ccRCC cells are not fully understood. This study investigated the roles of miR-141-3p and its target gene in regulating EMT in ccRCC development. 786-0 and Caki-1cells were treated with TGFß1 to induce EMT. The levels of miR-141-3p and TGFß2 were determined by quantitative real-time polymerase chain reaction and Western blotting. The progression of EMT was evaluated by E-cadherin detection by immunofluorescence, and E-cadherin, N-cadherin, and vimentin detection by Western blotting. Furthermore, migration and invasion capacities were assessed using a Transwell system. The direct binding of miR-141-3p with the target gene TGFß2 was confirmed by dual luciferase reporter gene assay. Results indicated that TGFß1 treatment decreased the protein abundance of E-cadherin while increasing the protein expression of N-cadherin and vimentin, indicating TGFß1-induced EMT was constructed successfully. Moreover, TGFß1 treatment repressed the expression of miR-141-3p. miR-141-3p mimics reversed the effect of TGFß1 on the migration, invasion, and expression of E-cadherin, N-cadherin, and vimentin. The miR-141-3p directly binds with the 3' untranslated region of TGFß2 mRNA and suppresses its expression. Furthermore, TGFß2 overexpression abrogated the above changes regulated by miR-141-3p mimics. Taken together, miR-141-3p inhibited TGFß1-induced EMT by suppressing the migration and invasion of ccRCC cells via directly targeting TGFß2 gene expression.

MicroRNA-141-3p reduces pulmonary hypoxia/reoxygenation injury through suppression of Beclin-1-dependent autophagy.

Alterations in autophagy are involved in pulmonary hypoxia/reoxygenation (H/R)-induced injury. Here, we intended to explain the function of microRNA-141-3p (miR-141-3p) in regulating autophagy under the H/R condition. Rat pulmonary microvascular endothelial cells (PMVECs) were applied for H/R cell model establishment, followed by tracing of autophagy formation. SIRT1 plays a critical role in controlling the lifespan of yeast, flies, and mice. Interaction between SIRT1 and Beclin-1, an indicator protein for autophagy, and between miR-141-3p and SIRT1 was assayed with their roles in PMVEC injury. Autophagy of PMVECs was activated after hypoxia treatment and further activated after H/R treatment. The binding of miR-141-3p and SIRT1 was verified. In H/R-treated PMVECs, the binding of miR-141-3p and SIRT1 was reduced. Furthermore, SIRT1 acted as a deacetylase to stabilize the Beclin-1 protein, promoting autophagy and PMVEC injury. H/R rat models were established, and in vivo, experiments further confirmed that miR-141-3p regulated autophagy and lung injury in H/R rats through SIRT1/Beclin-1 axis. The current study highlighted that reduced miR-141-3p in H/R-treated PMVECs promoted deacetylation of Beclin-1 by SIRT1, thus causing PMVEC injury.

CircCRIM1/microRNA-141-3p/thioredoxin-binding protein axis mediates neuronal apoptosis after cerebral ischemia-reperfusion.

Numerous studies have indicated enrichment of circular RNA (circRNA) in the brain takes on a momentous role in cerebral ischemia-reperfusion (CIR) injury. A recent study discovered a novel circCRIM1, was highly expressed in the middle cerebral artery occlusion-reperfusion (MCAO/R) model. Nevertheless, its specific biological function remained unknown. The study was to explore circCRIM1 in CIR-induced neuronal apoptosis. As measured, circCRIM1 and TXNIP were up-regulated, while miR-141-3p was down-regulated in MCAO/R mouse model and OGD/R SH-SY5Y cells. Depleting circCRIM1 reduced the number of apoptotic neurons in MCAO/R rats, increased the number of Nissl bodies, prevented reactive oxygen species production and oxidative stress imbalance in brain tissues, repressed cleaved caspase-3, Bax, and Cyto C protein levels and increased Bcl-2 levels. Overexpression of circCRIM1 further repressed neuronal activity and accelerated apoptosis in OGD/R model, disrupted redox balance. Depleting circCRIM1 had the opposite effect in OGD/R model. Knocking down miR-141-3p or TXNIP weakened the effects of knocking down circCRIM1 or overexpressing circCRIM1, separately. Mechanistically, circCRIM1 exerted an active role in CIR injury via miR-141-3p to mediate TXNIP. All in all, the circCRIM1/miR-141-3p/TXNIP axis might be a latent therapeutic target for CIR injury.

circ­LRP6 contributes to osteosarcoma progression by regulating the miR­141­3p/HDAC4/HMGB1 axis.

Circular RNA­lipoprotein receptor 6 (circ­LRP6) serves a role in promoting the tumorigenesis of retinoblastoma, esophageal squamous cell cancer and oral squamous cell carcinoma; however, whether circ­LRP6 demonstrates the same effect in osteosarcoma (OS) is yet to be fully elucidated. The present study aimed to analyze the expression, role and potential molecular mechanism of circ­LRP6 in OS. The expression levels of circ­LRP6, microRNA (miR)­141­3p, histone deacetylase 4 (HDAC4) and high mobility group protein 1 (HMGB1) were evaluated by reverse transcription-quantitative PCR in OS tissues and cell lines. Cell Counting Kit­8, Transwell and Matrigel assays were conducted to evaluate cell proliferation, migration and invasion, respectively. Western blotting was also performed to determine HDAC4 and HMGB1 protein expression levels. Bioinformatics and dual­luciferase reporter assays were used to predict and analyze the interactions between circ­LRP6 and miR­141­3p, miR­141­3p and HDAC4, as well as between miR­141­3p and HMGB1. Additionally, RNA immunoprecipitation was performed to verify the association between circ­LRP6 and miR­141­3p. The results confirmed that circ­LRP6 was highly expressed in OS tissues and cell lines. In addition, circ­LRP6 negatively regulated the expression of miR­141­3p and, in turn, miR­141­3p negatively regulated HDAC4 and HMGB1 expression. Functional assays revealed that circ­LRP6 knockdown inhibited the proliferation, migration and invasion of OS cells, whereas the inhibition of miR­141­3p or the overexpression of either HDAC4 or HMGB1 partly reversed the inhibitory effect of circ­LRP6 knockdown. In summary, the present study determined that circ­LRP6 knockdown inhibited the proliferation, migration and invasion of OS cells by regulating the miR­141­3p/HDAC4/HMGB1 axis.

MicroRNA-141-3p inhibits the progression of oral squamous cell carcinoma via targeting PBX1 through the JAK2/STAT3 pathway.

Oral squamous cell carcinoma (OSCC), which is the most common epithelial malignant neoplasm in the head and neck, is characterized by local infiltration and metastasis of lymph nodes. The five-year survival rate of OSCC remains low despite the advances in clinical methods. miR-141-3p has been shown to activate or inhibit tumorigenesis. However, the effects of miR-141-3p on invasion and migration of OSCC remain unclear. The present study aimed to evaluate the effects of miR-141-3p on invasion, proliferation, and migration in oral squamous cell carcinoma (OSCC). Reverse transcription quantitative PCR, western blotting and immunohistochemistry were used to detect microRNA(miR)-141-3p and pre-B-cell leukaemia homeobox-1 (PBX1) expression in OSCC tissues and cell lines. The luciferase reporter assay was used to detect targets of miR-141-3p in OSCC. MTT, Transwell and wound healing assays were used to determine the cell proliferation and invasive and migratory abilities, respectively. Expression of constitutive phosphorylated (p)-Janus kinase 2 (JAK2) and p-signal transducer and activator of transcription 3 (STAT3) was detected using western blotting in tissues and cells. miR-141-3p expression was decreased in OSCC tissues and cells, while PBX1 protein expression was increased compared with non-cancerous controls. The result from the dual-luciferase reporter assay revealed that PBX1 was the direct target of miR-141-3p in OSCC tissues. Furthermore, miR-141-3p overexpression and PBX1 knockdown could reduce cell invasion, proliferation and migration, and inhibit the JAK2/STAT3 pathway; however, miR-141-3p downregulation had the opposite effects. In addition, silencing of PBX1 using small interfering RNA could weaken the effects of miR-141-3p inhibitor on JAK2/STAT3 pathway and cell progression in CAL27 cells. In summary, the findings from this study indicated that miR-141-3p upregulation could inhibit OSCC cell invasion, proliferation and migration, by targeting PBX1 via the JAK2/STAT3 pathway.

Long non­coding RNA CTBP1­AS2 upregulates USP22 to promote pancreatic carcinoma progression by sponging miR­141­3p.

Long non­coding RNAs (lncRNAs) feature prominently in pancreatic carcinoma progression. The present study aimed to clarify the biological functions, clinical significance and underlying mechanism of lncRNA CTBP1 antisense RNA 2 (CTBP1­AS2) in pancreatic carcinoma. Reverse transcription­quantitative PCR was performed to assess the expression levels of CTBP1­AS2, microRNA (miR)­141­3p and ubiquitin­specific protease 22 (USP22) mRNA in pancreatic carcinoma tissues and cell lines. Western blotting was used to examine USP22 protein expression in pancreatic carcinoma cell lines. Loss­of­function experiments were used to analyze the regulatory effects of CTBP1­AS2 on proliferation, apoptosis, migration and invasion of pancreatic carcinoma cells. Dual­luciferase reporter assay was used to examine the binding relationship between CTBP1­AS2 and miR­141­3p, as well as between miR­141­3p and USP22. It was demonstrated that CTBP1­AS2 expression was markedly increased in pancreatic carcinoma tissues and cell lines. High CTBP1­AS2 expression was associated with advanced clinical stage and lymph node metastasis of patients. Functional experiments confirmed that knocking down CTBP1­AS2 significantly inhibited pancreatic carcinoma cell proliferation, migration and invasion, and promoted cell apoptosis. In terms of mechanism, it was found that CTBP1­AS2 adsorbed miR­141­3p as a molecular sponge to upregulate the expression level of USP22. In conclusion, lncRNA CTBP1­AS2 may be involved in pancreatic carcinoma progression by regulating miR­141­3p and USP22 expressions; in addition, CTBP1­AS2 may be a diagnostic biomarker and treatment target for pancreatic carcinoma.

Long non-coding RNA NEAT1 transported by extracellular vesicles contributes to breast cancer development by sponging microRNA-141-3p and regulating KLF12.

OBJECTIVE: Breast cancer (BC) remains a public-health issue on a global scale. Long non-coding RNAs (lncRNAs) play functional roles in BC. This study focuses on effects of NEAT1 on BC cell invasion, migration and chemotherapy resistance via microRNA (miR)-141-3p and KLF12. METHODS: After extraction and identification of serum extracellular vesicles (EVs), NEAT1 expression in EVs was detected and its association with clinical characteristics of BC patients was analyzed. Besides, the gain-of function was performed to investigate the roles of NEAT1 and miR-141-3p in BC, and levels of NEAT1, miR-141-3p, KLF12 and MDR1 after EV treatment were detected by RT-qPCR and Western blot analysis. Furthermore, the in vitro findings were confirmed via lung metastases in nude mice. RESULTS: NEAT1 expression in serum EVs was high and related to lymph node metastasis, progesterone receptor, estrogen receptor and Ki-67 in BC patients. After EV treatment, NEAT1 and KLF12 levels were increased, miR-141-3p expression was decreased, the abilities of proliferation, invasion, migration and in vivo metastasis were enhanced, and the sensitivity of cells to cisplatin, paclitaxel and 5-fluorouracil was decreased. After NEAT1 interference, NEAT1 and KLF12 levels in BC cells treated with EVs were decreased, miR-141-3p expression was increased, cell proliferation, invasion, migration and in vivo metastasis were decreased, and drug resistance sensitivity was increased. NEAT1 can bind to miR-141-3p and upregulates KLF12 expression. CONCLUSIONS: EVs inhibit the regulation of KLF12 by miR-141-3p by transporting NEAT1 to BC cells, thus promoting BC cell invasion, migration, and chemotherapy resistance.

lncRNA­MALAT1 promotes high glucose­induced H9C2 cardiomyocyte pyroptosis by downregulating miR­141­3p expression.

Diabetic cardiomyopathy (DCM) is caused by diabetes and can result in heart failure. Long non­coding RNAs (lncRNAs) have been demonstrated to be closely associated with DCM development. The present study aimed to investigate whether lncRNA­metastasis­associated lung adenocarcinoma transcript­1 (MALAT1) altered high glucose (HG)­induced H9C2 cardiomyocyte pyroptosis by targeting microRNA (miR)­141­3p. H9C2 cells were treated with normal glucose (NG) or HG. lncRNA­MALAT1 and miR­141­3p expression levels were determined via reverse transcription­quantitative PCR (RT­qPCR). MALAT1 and miR­141­3p knockdown and overexpression were established and confirmed via RT­qPCR. The association between MALAT1 expression and miR­141­3p expression, as well as the induction of pyroptosis and gasdermin D (GSDMD)­N expression were evaluated by performing dual luciferase reporter, TUNEL staining and immunofluorescence staining assays, respectively. Western blotting was conducted to measure the expression levels of pyroptosis­associated proteins, including apoptosis­associated speck­like protein, GSDMD­N, caspase­1, nucleotide oligomerization domain­like receptor protein 3 and GSDMD. MALAT1 mRNA expression levels were significantly increased, whereas miR­141­3p expression levels were significantly decreased in HG­treated H9C2 cells compared with the NG group. Compared with the HG group, MALAT1 overexpression significantly reduced miR­141­3p expression levels, increased the rate of TUNEL positive cells and upregulated the expression levels of pyroptosis­associated proteins. MALAT1 knockdown displayed the opposite effect on the rate of TUNEL positive cells and the expression levels of pyroptosis­associated proteins. Furthermore, the rate of TUNEL positive cells, and GSDMD­N and pyroptosis­associated protein expression levels were significantly reduced by miR­141­3p overexpression in MALAT1­overexpression H9C2 cells. The results indicated that compared with NG treatment, HG treatment increased MALAT1 expression levels and decreased miR­141­3p expression levels in H9C2 cells. Therefore, the present study suggested that lncRNA­MALAT1 targeted miR­141­3p to promote HG­induced H9C2 cardiomyocyte pyroptosis.

MicroRNA-141-3p expression in serum of patients with cerebral hemorrhage and its mechanism / 解剖学报

Objective To analyze the expression level of microRNA-141-3p (miR-141-3) in patients with intracerebral hemorrhage (ICH), and explore the effect and mechanism of miR-141-3p on cerebral hemorrhage injury in rats. Methods Forty patients with ICH and 40 healthy controls in total were enrolled in this study. The expression of miR- 141-3p in peripheral blood serum was determined by the Real-time PCR method. The target relationship between miR-141- 3p and NOD-like receptor 3 (NLRP3) 3′ UTR was confirmed by dual luciferase reporter assay. miR-141-3p agonist and agonist NC were injected into rats via the lateral ventricle, respectively. On day 7 after treatment, the neurological function score was evaluated, and then all rats were killed to obtain brain tissue. Brain water content was examined by the dried and wet mass. HE staining was conducted to observe the pathological changes of cerebral tissue. The mRNA expressions of NLRP3 and miR-141-3p were detected by Real-time PCR. The protein expression of interleukin (IL)-lβ, IL-6 and IL-18 were detected by Western blotting analysis. Results The expression of miR-141-3p in serum of ICH patients was significantly down-regulated compared to healthy controls and negatively correlated with the severity of edema around the hematoma [(0.068±0.038) vs (0.520±0.028), t = 15.93, P<0.001; r =-0.8948, -0.9434 to-0.8087, P<0.001 ]. The result of luciferase reporter assay showed that miR-141-3p was related to the regulation of NLRP3 gene expression. The relative expression levels of miR-141-3p in agonist group were significantly higher than those in the agonist NC group (P< 0.001), while the expression levels of NLRP3, IL-lβ, IL-6 and IL-18 were significantly lower than those in the agonist NC group (P< 0.001). Compared with the agonist NC group, the cerebral water content reduced significantly (P< 0.001), and the neurological function score was significantly improved on the day 7 after treatment in agonist group (P< 0.001). The result of HE staining showed that injection of miR-141-3p in ICH rats could reduced the severity of edema around the hematoma. Conclusion MiR-141-3p alleviates ICH-induced inflammatory injury in rat possibly by modulating miR-141-3p.

Significances of the plasma expression of microRNA-101-3p and microRNA-141-3p in children with sepsis / 中华实用儿科临床杂志

Objective:To examine the plasma expression levels and clinical significances of microRNA(miR)-101-3p and miR-141-3p in children with sepsis.Methods:One hundred and fifty-three children with sepsis admitted in Sanya People′s Hospital from January 2016 to October 2019 were divided into sepsis without shock group (94 cases) and septic shock group (59 cases). In addition, they were further divided into survival group (107 cases) and death group (46 cases) according to the 28-day survival.Another 60 healthy children were selected as the healthy control group.Real-time fluorescence quantitative polymerase chain reaction (RT-PCR) was performed to detect plasma levels of miR-101-3p and miR-141-3p in all subjects.Receiver operating characteristic curve(ROC) were depicted to identify the diagnostic and prognostic potentials of plasma miR-101-3p, miR-141-3p and procalcitonin(PCT) in sepsis. Pearson′ s correlation analysis was performed to analyze the correlation between the expression levels of miR-101-3p, miR-141-3p and PCT with Acute Physiology and Chronic Health Evaluation Ⅱ(APACHE Ⅱ)score, Sequential Organ Failure Assessment(SOFA)score, leukocyte count and C-reactive protein level in children with sepsis. Results:Plasma levels of miR-101-3p, miR-141-3p and PCT in septic shock group and sepsis without shock group were significantly higher than those in the healthy control group (all P<0.001). Moreover, plasma levels of miR-101-3p (4.25±1.46 vs.1.86±0.75), miR-141-3p (3.17±1.08 vs.1.20±0.52) and PCT [(20.75±9.36) μg/L vs.(5.80±2.40) μg/L] in septic shock group were significantly higher than those in sepsis without shock group (all P<0.001). In addition, plasma levels of miR-101-3p, miR-141-3p and PCT in survival group and death group were significantly higher than those in the healthy control group (all P<0.001). Notably, plasma levels of miR-101-3p (4.83±1.62 vs.1.40±0.58), miR-141-3p (3.50±1.13 vs.0.96±0.47), and PCT [(26.30±11.72) μg/L vs.(3.25±2.16) μg/L] in death group were significantly higher than those in the survival group (all P<0.001). ROC curve analysis showed that the area under the curve (AUC) and 95% confidence interval (95% CI) of the combined diagnosis of sepsis with miR-101-3p, miR-141-3p and PCT were significantly higher than that of miR-101-3p, miR-141-3p or PCT alone [0.908 (0.850-0.970) vs.0.810 (0.748-0.873), 0.784 (0.723-0.844) and 0.825 (0.764-0.883), respectively; Z1=4.682, Z2=5.380 and Z3=4.417, all P<0.05]. The sensitivity and specificity of the combined diagnosis was 92.5% and 84.0%, respectively.The AUC and 95% CI of the combined prediction of miR-101-3p, miR-141-3p and PCT in the mortality of children with sepsis children with were significantly higher than those with miR-101-3p, miR-141-3p or PCT alone [0.930 (0.872-0.986) vs.0.848 (0.786-0.907), 0.792 (0.730-0.853) and 0.820 (0.762-0.878), respectively; Z1=4.537, Z2=5.728 and Z3=5.106, all P<0.05]. The sensitivity and specificity of the combined prediction in the mortality was 94.6%, and 87.0%, respectively.Correlation analysis showed that miR-101-3p and miR-141-3p levels were positively correlated with PCT ( r=0.804, 0.773, all P<0.001), APACHE Ⅱ score ( r=0.738, 0.695, P<0.001) and SOFA score ( r=0.752, 0.764, all P<0.001). Conclusions:Plasma levels of miR-101-3p and miR-141-3p in children with sepsis significantly increased, which are correlated with the severity of sepsis.A combination detection of miR-101-3p, miR-141-3p and PCT has high diagnostic and prognostic potentials in children with sepsis.

Long non-coding RNA ATB is associated with metastases and promotes cell invasion in colorectal cancer via sponging miR-141-3p.

Long non-coding RNAs (lncRNAs) serve crucial roles in cancer development and progression. lncRNA-activated by transforming growth factor-ß (lncRNA-ATB) mediates cell proliferation. However, the association between lncRNA-ATB and human colorectal cancer (CRC) is not completely understood. Therefore, the present study aimed to investigate the role of lncRNA-ATB in CRC, as well as the underlying mechanism. 50 pairs of tumor tissues and adjacent normal tissues from patients with primary CRC were collected. The expression of lncRNA-ATB and microRNA (miR)-141-3p in CRC tissues, adjacent normal tissues and cell lines was detected using reverse transcription-quantitative PCR. CCK-8, colony formation, Transwell, western blot, dual luciferase reporter gene, RNA immunoprecipitation and immunohistochemistry staining assays were conducted to assess the biological function of lncRNA-ATB and miR-141-3p in CRC progression. lncRNA-ATB was upregulated in CRC tissues and cell lines compared with healthy tissues and cells, respectively. Moreover, high expression of lncRNA-ATB was significantly associated with advanced TNM stage and metastasis in CRC. In addition, the results indicated that lncRNA-ATB expression predicted the prognosis and overall survival of patients with CRC. Compared with small interfering RNA-negative control, lncRNA-ATB knockdown inhibited CRC cell proliferation, migration and invasion, whereas, compared with vector, lncRNA-ATB overexpression promoted CRC cell proliferation, migration and invasion. Furthermore, the in vivo experiment suggested that lncRNA-ATB knockdown inhibited tumor growth. The results also indicated that lncRNA-ATB may contribute to CRC progression via binding to tumor suppressor microRNA-141-3p. Collectively, the present study suggested a crucial role of lncRNA-ATB in CRC tumorigenesis, suggesting that lncRNA-ATB may serve as an important marker for the diagnosis and development of CRC.

Increased Expression of microRNA-141-3p Improves Necrotizing Enterocolitis of Neonates Through Targeting MNX1.

Objective: MicroRNA-141-3p (miR-141-3p) has been investigated in various kinds of cancers. This research delves into the functions and regulatory mechanisms of miR-141-3p in necrotizing enterocolitis (NEC) of neonates. Methods: NEC tissues were obtained from neonatal mice, and subsequently, expression of miR-141-3p and motor neuron and pancreas homeobox 1 (MNX1) was assayed via RT-qPCR. Moreover, the intestinal histopathological changes and histiocytic apoptosis were observed via hematoxylin and eosin (H&E) and TUNEL staining. The correlative inflammatory factors and oxidative stress markers were evaluated to uncover the influence of miR-141-3p in NEC tissue damage. Further, the relation between MNX1 and miR-141-3p was predicated, and the functions of MNX1 in inflammatory response and cell growth of IEC-6 cells were investigated. Results: Downregulated miR-141-3p and upregulated MNX1 were discovered in NEC tissues. Moreover, miR-141-3p clearly alleviated inflammation response and oxidative stress damage in NEC, which was achieved through regulating inflammatory cytokines (IL-1ß, IL-6, and TNF-α) and oxidative stress markers (MPO, MDA, and SOD) expression. MNX1 was forecasted as a target gene of miR-141-3p; meanwhile, MNX1 overexpression overturned the influence of miR-141-3p in the inflammatory response and cell growth process of IEC-6 cells. Conclusion: These explorations reveal that increased expression of miR-141-3p could improve the damage to intestinal tissues in NEC through targeting MNX1. The research might exhibit a neoteric therapeutic strategy for NEC.

MiR-141-3p ameliorates RIPK1-mediated necroptosis of intestinal epithelial cells in necrotizing enterocolitis.

AIM: To explore the effects of miR-141-3p on intestinal epithelial cells in necrotizing enterocolitis and the underlying mechanism. RESULTS: The expression of miR-141-3p was significantly downregulated in serum samples of patients with NEC and LPS-treated Caco-2 cells. The in vitro assays showed that miR-141-3p mimics inhibited expression of IL-6 and TNF-α and reduced PI positive rate of the LPS-treated Caco-2 cells. Next, receptor interacting protein kinase 1 (RIPK1) was identified as the downstream molecule of miR-141-3p, and RIPK1 overexpression aggravated LPS-induced Caco-2 cell injury, which was ameliorated by miR-141-3p mimics. Finally, we found miR-141-3p mimics inhibited upregulation of necroptosis-related molecules and interaction of RIPK1 and RIPK3 in LPS-treated Caco-2 cells. CONCLUSION: Our research indicated that miR-141-3p protected intestinal epithelial cells from LPS damage by suppressing RIPK1-mediated inflammation and necroptosis, providing an alternative perspective to explore the pathogenesis of NEC. METHODS: Quantitative real time-polymerase chain reaction (qRT-PCR) was used to detect the expression of miR-141-3p in serum samples of participants and lipopolysaccharide (LPS)-treated Caco-2 cells. Cell Counting Kit-8 (CCK-8) assay, Propidium Iodide (PI) staining and detection of inflammatory cytokines were performed to evaluate the role of miR-141-3p in LPS-treated Caco-2 cells. TargetScanHuman database and luciferase reporter gene assay were utilized to confirm the direct downstream molecule of miR-141-3p. Western blot analysis was used to explore the mechanism.

STAT4 silencing underlies a novel inhibitory role of microRNA-141-3p in inflammation response of mice with experimental autoimmune myocarditis.

As an inflammatory disease afflicting the heart muscle, autoimmune myocarditis (AM) represents one of the foremost causes of heart failure. Accumulating evidence has implicated microRNAs (miRNAs) in the process of inflammation and autoimmunity. Hence, the current study aimed to investigate the mechanism by which miR-141-3p influences experimental AM (EAM). An EAM mouse model was established using 6-wk old male BALB/c mice, after which the expression of miR-141-3p and STAT4 was measured. Gain-of-function and loss-of-function investigations were performed to identify the functional role of miR-141-3p and STAT4 in EAM. Heart weight-to-body weight ratio, cardiac function, and degree of inflammation, as well as the levels of inflammation factors (IFN-γ, TNF-α, IL-2, IL-6, and IL-17) in the serum were detected. STAT4 was subsequently verified to be upregulated, and miR-141-3p was downregulated in the EAM mice. Furthermore, the overexpression of miR-141-3p or silencing of STAT4 was observed to reduce the heart weight-to-body weight ratio of EAM mice and improve cardiac function, while alleviating the degree of inflammatory cell infiltration in the myocardial tissue. Meanwhile, the overexpression of miR-141-3p was identified to diminish serum inflammatory factor levels by downregulating STAT4. Additionally, miR-141-3p could bind to STAT4 to downregulate its expression, ultimately mitigating inflammation and inducing an anti-inflammatory effect in EAM mice. Taken together, upregulation of miR-141-3p alleviates the inflammatory response in EAM mice by inhibiting STAT4, providing a promising intervention target for the molecular treatment of AM.NEW & NOTEWORTHY miR-141-3p is poorly expressed, and STAT4 is upregulated in experimental autoimmune myocarditis (EAM) mice. Overexpressing miR-141-3p inhibits EAM. miR-141-3p binds to and suppresses STAT4 expression. miR-141-3p overexpression inhibits inflammatory factors by downregulating STAT4. This study provides new insights into the treatment of autoimmune myocarditis.

MicroRNA-141-3p inhibits retinal neovascularization and retinal ganglion cell apoptosis in glaucoma mice through the inactivation of Docking protein 5-dependent mitogen-activated protein kinase signaling pathway.

Retinal neovascularization occurs in various ocular disorders including proliferative diabetic retinopathy and secondary neovascular glaucoma, resulting in blindness. This paper aims to investigate the effect of microRNA-141-3p (miR-141-3p) on retinal neovascularization and retinal ganglion cells (RGCs) in glaucoma mice through the Docking protein 5 (DOK5)-mediated mitogen-activated protein kinase (MAPK) signaling pathway. Chip retrieval and difference analysis were used for the potential mechanism of miR-141-3p on glaucoma. All modeled mice were transfected with different expression of mimic or inhibitor. The expressions of miR-141-3p, DOK5, and related genes and proteins of the MAPK signaling pathway were detected by Reverse transcription quantitative polymerase chain reaction and western blot analysis. Cell proliferation, lumen formation, and apoptosis in the retinal vascular epithelial cells and RGCs were detected using Matrigel angiogenesis and terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling assays. Moreover, a total of 63 and 294 differentially expressed genes were obtained in GSE2378 and GSE9944 chips, and 4 genes were within the intersection of the chips. In addition, the results showed that miR-141-3p was found to inhibit the DOK5 gene and activate the MAPK pathway. The number of RGCs, the expression of p38, extracellular-signal-regulated kinases (ERK), Jun N-terminal kinase (JNK), IGF-1, VEGF, HIF1-α, Bax, caspase-3, and the extent of p38, ERK, and JNK phosphorylated were decreased with miR-141-3p upregulation. Lastly, the results obtained showed that miR-141-3p inhibited the proliferation of retinal vascular epithelial cells and inhibited angiogenesis, as well as promoted apoptosis of RGCs. The study suggests that miR-141-3p inhibits retinal neovascularization in glaucoma mice by impeding the activation of the DOK5-mediated MAPK signaling pathway.

Propofol Inhibits Neurogenesis of Rat Neural Stem Cells by Upregulating MicroRNA-141-3p.

Prolonged or high-dose exposure to anesthetics, such as propofol, can cause brain cell degeneration and subsequent long-term learning or memory deficits, particularly in the developing brain. However, the cellular and molecular mechanisms underlying the deleterious effects of propofol at certain stages of development remain unclear. In this study we found that propofol inhibited the proliferation, neuronal differentiation, and migration of neural stem cells (NSCs) while upregulating miR-141-3p. Silencing of miR-141-3p abrogated the effects of propofol on NSC neurogenesis. Propofol treatment downregulated IGF2BP2, a direct target of miR-141-3p, whereas overexpression of IGF2BP2 attenuated the effects of propofol and miR-141-3p on NSC neurogenesis. In short, propofol inhibits NSC neurogenesis through a mechanism involving the miR-141-3p/IGF2BP2 axis. Our results may provide a potential approach for preventing the neurodegenerative effects of propofol in the developing brain.