Myocardial ischemia/reperfusion (I/R) injury is a major pathological process in coronary heart disease and cardiac surgery, and is associated with aberrant microRNA (miR) expression. Previous studies have demonstrated that inhibition of miR-15a expression may ameliorate I/R‑induced myocardial injury. In the present study, the potential role and underlying mechanism of miR‑15a in hypoxia/reoxygenation‑induced apoptosis of cardiomyocytes was investigated. Myocardial I/R was simulated in cultured H9c2 cells by 24 h hypoxia followed by 24 h reoxygenation. Using recombinant lentivirus vectors, the inhibition of miR‑15a was indicated to significantly reduce cardiomyocyte apoptosis and release of lactate dehydrogenase and malondialdehyde. Conversely, upregulated miR‑15a expression was pro‑apoptotic. Mothers against decapentaplegic homolog 7 (SMAD7) was identified by bioinformatics analysis as a potential target of miR‑15a. Luciferase reporter assays and western blotting for endogenous SMAD7 protein indicated that miR‑15a inhibited SMAD7 expression via its 3'‑untranslated region. Nuclear levels of nuclear factor‑κB (NF‑κB) p65 were increased by miR‑15a expression and decreased by miR‑15a inhibition, which is consistent with the possibility that the inhibition of SMAD7 by miR-15a results in NF‑κB activation. These findings suggested that the therapeutic effects of miR‑15a inhibition on I/R injury may potentially be explained by its ability to release SMAD‑7‑dependent NF‑κB inhibition. This may provide evidence for miR‑15a as a potential therapeutic target for the treatment of cardiac I/R injury.

The ability of mesenchymal stem cells (MSCs) to differentiate into osteogenic lineages requires management for their future use in treating bone destruction and osteoporosis. Hepcidin is closely associated with bone metabolism, however, it remains to be elucidated whether hepcidin affects osteogenic differentiation in MSCs. The present study demonstrated that hepcidin enhanced osteoblastic differentiation and mineralization, which was manifested by an upregulation in the differentiation markers alkaline phosphatase and osteogenic genes. Furthermore, the expression levels of bone morphogenetic proteins and small mothers against decapentaplegic homologs were concomitantly increased following hepcidin treatment. In addition, the p38 mitogen-activated protein kinase may be an upstream kinase for osteoblastic differentiation. Thus, hepcidin may be important in the osteogenic differentiation of MSCs and may be considered as a target in the development of therapies for pathological bone loss.

Lonicera japonica has been used in traditional Chinese medicine as an important medicinal plant, with the ability to inhibit osteoclast development and bone loss. However, it is not clear which active ingredient exerts these effects. (R)‑dehydroxyabscisic alcohol β‑D‑apiofuranosyl‑(1ˮ→6')‑β‑D‑glucopyranoside (DAG) is an active constituent isolated from Lonicera japonica. In the present study, the ST2 bone marrow stromal cell line was treated by DAG at different concentrations and the osteoblastic differentiation was explored by ELISA assay, Von Kossa staining, Alizarin Red S staining, reverse transcription‑quantitative polymerase chain reaction and western blot analysis. The results revealed that DAG promoted osteoblastic differentiation, as evidenced by increasing mineralization and alkaline phosphatase (ALP) activity, as well as the expression of genes encoding bone differentiation markers, including Alp, osteopontin (Opn) and osteocalcin (Ocn). In addition, DAG upregulated the gene expression of bone morphogenetic protein (Bmp)‑2, Bmp4, Wnt family member (Wnt)‑1, Wnt3 and runt‑related transcription factor 2 (Runx2), as well as the protein expression of phosphorylated‑mothers against decapentaplegic homolog (Smad) 1, Smad5 Smad8, β‑catenin and Runx2 in ST2 cells. The osteogenic effects induced by DAG were attenuated by the BMP antagonist Noggin and the WNT signaling pathway inhibitor Dickkopf related protein‑1. The data indicated that DAG promoted the osteoblastic differentiation of ST2 cells, at least partially through regulating the BMP/WNT signaling pathways. This provides scientific rationale for the development of DAG as a treatment for bone loss‑associated diseases, such as osteoporosis.

Our previous study indicated that loureirin A induces hair follicle stem cell (HFSC) differentiation through Wnt/β‑catenin signaling pathway activation. However, if and how microRNAs (miRNAs/miRs) modulate loureirin A‑induced differentiation remains to be elucidated. In the present study, HFSCs were separated from the vibrissae of rats and identified by CD34 and keratin, type 1 cytoskeletal (K)15 expression. Microarray‑based miRNA profiling analysis revealed that miR‑339‑5p was downregulated in loureirin A‑induced HFSC differentiation. miR‑339‑5p overexpression by transfection with miR‑339‑5p mimics markedly inhibited the expression of K10 and involucrin, which are markers of epidermal differentiation, whereas inhibition of miR‑339‑5p by miR‑339‑5p inhibitor transfection promoted the expression of K10 and involucrin. These results suggest that miR‑339‑5p is a negative regulator of HFSC differentiation following induction by loureirin A. These findings were confirmed by a luciferase assay. Homeobox protein DLX‑5 (DLX5) was identified as a direct target of miR‑339‑5p. Furthermore, it was demonstrated that miR‑339‑5p inhibited DLX5. Overexpression of miR‑339‑5p by mimic transfection significantly inhibited protein Wnt‑3a (Wnt3a) expression, while inhibition of miR‑339‑5p by inhibitor transfection significantly increased the expression of Wnt3a. Furthermore, small interfering RNA targeting DLX5 was transfected into HFSCs, and western blot analysis revealed that Wnt3a, involucrin and K10 expression was significantly downregulated. Taken together, these results suggest that miR‑339‑5p negatively regulated loureirin A‑induced HFSC differentiation by targeting DLX5, resulting in Wnt/β‑catenin signaling pathway inhibition. This may provide a possible therapeutic target for skin repair and regeneration.

10‑Hydroxycamptothecin (HCPT) effectively controls epidural fibrosis, but the exact underlying mechanisms remain ambiguous. Abnormal microRNA (miR)‑23b‑3p expression has been detected in various types of fibrotic tissues that are present in different diseases. The aim of the present study was to elucidate the mechanisms through which HCPT induces fibroblast apoptosis. Reverse transcription‑quantitative polymerase chain reactions were performed on six traumatic scar samples and matched normal skin samples; traumatic scar formation was revealed to be significantly inversely associated with miR‑23b‑3p expression. In addition, the miR‑23b‑3p expression level in human fibroblasts was examined following HCPT treatment. The effects of HCPT and miR‑23b‑3p on fibroblast apoptosis were assessed using terminal deoxynucleotidyl‑transferase‑mediated dUTP nick‑end labeling, flow cytometry and western blot analysis. The results demonstrated that HCPT treatment notably increased miR‑23b‑3p expression levels and accelerated fibroblast apoptosis. Therefore, upregulation of miR‑23b‑3p expression was demonstrated to promote fibroblast apoptosis, consistently with the effects of HCPT. The results of the present study indicated that HCPT may induce fibroblast apoptosis by regulating miR‑23b‑3p expression.

Keloids are a type of abnormal scar tissue. MicroRNAs (miRNAs) exhibit a pivotal role in the regulation of cell proliferation and metastasis of keloids. miRNA microarray revealed that miR‑637 was one of the most frequently altered miRNAs in keloids. Furthermore, up-regulation of miR‑637 inhibited cell proliferation and metastasis by targeting mothers against decapentaplegic homolog (Smad)3, one of the important proteins that affects the formation of keloids. Further studies demonstrated that miR‑637 regulated the proliferation and metastasis of human keloid fibroblast (HKF) cells by mediating the Smad3 signaling pathway. Overall, the present findings suggest that miR‑637 may be a promising therapeutic target in keloids.

Obesity represents a global health and economic burden, affecting millions of individuals worldwide. This pathology is associated with a chronic low‑grade inflammatory state that is partially responsible for the development of other cardiometabolic complications. Clinical studies have reported an association between high circulating levels of lipocalin‑2 (Lcn2) and increased body weight. Additionally, there is scientific evidence demonstrating the impact of maternal obesity on fetal programming. The latter and the fact that the authors previously found that Lcn2 and its receptor (24p3R) are expressed in the gonads of wild‑type rats, led to the analysis of their mRNA profile and cellular localization in gonads collected from the offspring of obese rats at 21 days postconception (dpc), and 0, 2, 4, 6, 12, 20 and 30 days postnatal (dpn) in the present study. Semi‑quantitative PCR revealed a statistically significant downregulation of Lcn2 and 24p3R mRNA at 21 dpc in the ovaries (P<0.01) and testicles (P<0.001) of the offspring of obese mothers. At 30 dpn, the relative expression of Lcn2 mRNA decreased significantly in the ovaries of the experimental group (P<0.05), while Lcn2 mRNA expression was not detectable in testicles. Regarding 24p3R, its mRNA was only significantly decreased at 21 dpc in ovaries of pups of obese mothers. At 30 dpn, the change in females was not significant. Conversely, in testicles, 24p3R mRNA levels increased slightly in the experimental group at 30 dpn. The Lcn2 protein signal was less intense in gonadal tissue sections from 30 dpn offspring of obese rats (P<0.001), whereas the 24p3R signal was downregulated in ovaries (P<0.001) and slightly upregulated in testicles. It was concluded that maternal obesity changes the expression of Lcn2 and 24p3R in the gonads of the offspring of obese rats, possibly through fetal programming. The consequences of this dysregulation for the offspring's gonadal function remains to be determined.

Maternal diabetes has been reported to be a critical factor for congenital heart defects (CHD) in offspring. The present study aimed to screen the key genes that may be involved in CHD in offspring of diabetic mothers. The present study obtained the gene expression profile of GSE32078, including three embryonic heart tissue samples at embryonic day 13.5 (E13.5), three embryonic heart tissue samples at embryonic day 15.5 (E15.5) from diabetic mice and their respective controls from normal mice. The cut‑off criterion of P<0.08 was set to screen differentially expressed genes (DEGs). Their enrichment functions were predicted by Gene Ontology. The enriched pathways were forecasted by Kyoto Encyclopedia of Genes and Genomes and Reactome analysis. Protein‑protein interaction (PPI) networks for DEGs were constructed using Cytoscape. The present study identified 869 and 802 DEGs in E13.5 group and E15.5 group, respectively and 182 DEGs were shared by the two developmental stages. The pathway enrichment analysis results revealed that DEGs including intercellular adhesion molecule 1 (Icam1) and H2‑M9 were enriched in cell adhesion molecules; DEGs including bone morphogenetic protein receptor type 1A, transforming growth factor β receptor 1 and SMAD specific E3 ubiquitin protein ligase 1 were enriched in the tumor growth factor‑β signaling pathway. In addition, DEGs including Icam1, C1s and Fc fragment of IgG receptor IIb were enriched in Staphylococcus aureus infection. Furthermore, the shared DEGs including Icam1, nuclear receptor corepressor 1 (Ncor1) and AKT serine/threonine kinase 3 (Akt3) had high connectivity degrees in the PPI network. The shared DEGs including Icam1, Ncor1 and Akt3 may be important in the cardiogenesis of embryos. These genes may be involved in the development of CHD in the offspring of diabetic mothers.

The aim of the present study was to examine the regulatory mechanism underlying the depression in Ski‑related novel protein N (SnoN) in diabetic nephrology (DN). NRK‑52E cells, a rat primary renal tubular epithelial cell line, were cultured to clarify the effect of small mothers against decapentaplegic (Smad) ubiquitination regulatory factor 2 (smurf2) on SnoN in a low glucose environment in vitro. NRK‑52E cells and DM rats were injected with adenoviruses AD‑smurf2 and AD‑shsmurf2, respectively, and the protein expression profiles of SnoN, smurf2 and phosphorylated (p)‑Smad2 were then detected. In addition, the protein levels of smurf2, p‑Smad2 and SnoN were analyzed following treatment with transforming growth factor (TGF)‑β1 or TGF‑β1 inhibitor to validate the effect of the TGF‑β1/Smad signaling pathway. The effect of smurf2 on the degradation of SnoN by ubiquitination was found to be a key factor in DN, which was mediated by the TGF‑β1/Smad signaling pathway.

Gliomas are the most frequently occurring primary tumor in the brain. The most malignant form of glioma, glioblastoma multiforme (GBM), is characterized by rapid and invasive growth and is restricted to the central nervous system (CNS). The transforming growth factor β2 (TGFβ2)/small mothers against decapentaplegic (Smad) signaling pathway is important, not only in GBM cell metabolism and invasion, but also in GBM cell proliferation. However, the functions of the downstream mediators of the TGFβ2/Smads signaling pathway remain to be fully elucidated. In the present study, short hairpin (sh)RNA interference was used to specifically inhibit the expression of Smad2 and Smad3 in the TGFβ2/Smad signaling pathway to investigate the effects of shRNA on the proliferation of human GBM cells. The results demonstrated that knockdown of either Smad2 or Smad3 enhanced cellular proliferation. Additionally, the key target genes involved in GBM cell proliferation, induced by TGFβ2, were found to be dependent on Smad3, but not Smad2.

Studies have shown that cannabinoid CB2 receptors are involved in wound repair, however, its physiological roles in fibrogenesis remain to be elucidated. In the present study, the capacity of cannabinoid CB2 receptors in the regulation of skin fibrogenesis during skin wound healing was investigated. To assess the function of cannabinoid CB2 receptors, skin excisional BALB/c mice were treated with either the cannabinoid CB2 receptor selective agonist, GP1a, or antagonist, AM630. Skin fibrosis was assessed by histological analysis and profibrotic cytokines were determined by immunohistochemistry, immunofluorescence staining, reverse transcription‑quantitative polymerase chain reaction and immunoblotting in these animals. GP1a decreased collagen deposition, reduced the levels of transforming growth factor (TGF)‑β1, TGF‑β receptor I (TβRI) and phosphorylated small mothers against decapentaplegic homolog 3 (P‑Smad3), but elevated the expression of its inhibitor, Smad7. By contrast, AM630 increased collagen deposition and the expression levels of TGF‑β1, TβRI and P‑Smad3. These results indicated that cannabinoid CB2 receptors modulate fibrogenesis and the TGF‑β/Smad profibrotic signaling pathway during skin wound repair in the mouse.

The increasing burden of diabetes in low and middle‑income countries is attributable to both genetic and epigenetic factors. Environmental‑ and lifestyle‑associated changes are also considered to be important contributors to this disease. The resultant co‑morbidities arising from micro‑and macrovascular changes in diabetes are difficult to manage and are an economic burden. However, very little is known about the molecular mechanisms that drive this phenotype. The present study aimed to investigate the role of sirtuin 1 (SIRT1)‑ and transcription box‑3 (TBX‑3)‑mediated regulation of endothelial dysfunction, given the significance of SIRT1 in glucose metabolism and the role of TBX‑3 in the maintenance of cellular proliferation, senescence and apoptosis. Following the recruitment of adult patients with and without diabetes, both SIRT1 and TBX‑3 expression was confirmed to be present in the sera of the patients with diabetes and the patients without diabetes; however, both SIRT1 and TBX‑3 expression levels were higher in the sera of the patients with diabetes. Human umbilical vein endothelial cells (HUVECs) were further used for in vitro studies. Using TBX‑3 and SIRT1 knockdown models, the cellular responses to proliferation, migration, invasion and tube formation were investigated using an MTS, cell cycle analysis, wound healing, Transwell and tube formation assay, respectively. Western blotting was also used to determine the downstream signaling pathways involved. The genetic knockdown of TBX‑3 in hyperglycemic conditions significantly decreased the cellular proliferation, migration, invasion and angiogenesis of HUVECs. It was subsequently identified that TBX‑3 mediated its effects through the activation of AKT and vascular endothelial growth factor (VEGF) signaling. However, the genetic knockdown of SIRT1 in the presence of TBX‑3 overexpression and glucose failed to activate the AKT and VEGF signaling pathways. In conclusion, the results of the present study suggested that SIRT1 may positively regulate TBX‑3 in endothelial cells, therefore, SIRT1 and/or TBX‑3 may serve as potential novel biomarkers for disease progression.

Pre-eclampsia (PE) is a common but complex condition that can occur in pregnancy. It is estimated to affect 3-8% of pregnancies worldwide. PE development is thought to be multifactorial and to involve the dysregulation of microRNA (miR) expression. However, the precise mechanisms of PE development remain unclear. The present study aimed to illustrate the association between miR‑203 expression and PE development in samples of human placenta collected from mothers with (n=18) and without (n=20) PE. It was demonstrated that miR‑203 expression was significantly increased in the PE placenta compared with the normal placenta samples, while the expression of vascular endothelial growth factor A (VEGFA) was decreased. In vitro experiments revealed that miR‑203 overexpression significantly downregulated VEGFA expression and inhibited the proliferation, migration and invasion ability of HTR‑8/SVneo cells. Suppression of miR‑203 expression alleviated these effects. A luciferase reporter assay confirmed the interaction of the 3'‑untranslated region of VEGFA with miR‑203. Thus, miR‑203 may have significant contribution to the development of PE by targeting VEGFA in the human placenta and may have potential as a biomarker or therapeutic target in the treatment of PE.

Renal interstitial fibrosis (RIF) is the main process that leads to renal failure. It is necessary to investigate the mechanism of RIF and identify appropriate methods of regulating it. Furthermore, unilateral ureteral obstruction is a frequently used model for the study of RIF. The morphological damage associated with kidney and lung dysfunction was detected using histopathological experiments. Subsequently, high expression of reactive oxygen species (ROS) modulator 1 (ROMO1) and ROS was measured in blood serum. In addition, epithelial‑mesenchymal transition marker, transforming growth factor β (TGF‑β) and mothers against decapentaplegic homolog 2/3 expression was evaluated using the reverse transcription‑quantitative polymerase chain reaction and western blotting. All serious symptoms were relieved to a certain extent following oxidation inhibitor intervention using three common antioxidants. HK‑2 cells were treated with H2O2 to cause oxidative stress, and ROMO1 and fibrosis marker expression increased; however, activation was suppressed byROMO1 knockout. The present study provides evidence that the expression of ROMO1 induces ROS production and activates the TGF‑β signaling pathway. It may be concluded that ROMO1 helps to provide a molecular basis for improved clinical intervention and prognosis of patients.

Subconjunctival fibrosis represents the primary cause of postoperative failure of trabeculectomy, and at present there is a lack of effective intervention strategies. The present study aimed to investigate the effect of the mitogen‑activated protein kinase kinase (MEK) inhibitor U0126 on human tenon fibroblast (HTF) myofibrosis transdifferentiation, and to illuminate the underlying molecular mechanisms involved. It was demonstrated that U0126 significantly inhibited the proliferation, migration and collagen contraction of HTFs stimulated with TGF‑β1. In addition, U0126 largely attenuated the TGF‑β1‑induced conversion of HTFs into myofibroblasts, as indicated by a downregulation of the mRNA and protein expression of α‑smooth muscle actin and zinc finger protein SNAI1, and by ameliorating the 3D‑collagen contraction response. Mechanistically, U0126 suppressed the TGF‑β1‑stimulated phosphorylation of mothers against decapentaplegic homolog 2/3, P38 mitogen‑activated protein kinase and extracellular signal‑regulated kinase 1/2, indicating that U0126 may inhibit HTF activation through the canonical and non‑canonical signaling pathways of TGF‑β1. Therefore, U0126 exhibits a potent anti‑fibrotic effect among HTFs, and the inhibition of MEK signaling may serve as an alternative intervention strategy for the treatment of trabeculectomy‑associated fibrosis.

Long noncoding RNAs (lncRNAs) are associated with various diseases including cataracts. The role of lncRNA potassium voltage‑gated channel subfamily Q member 1 opposite strand/antisense transcript 1 (KCNQ1OT1) on lens epithelial cell (LEC) proliferation and epithelial‑mesenchymal transition (EMT) in cataracts disease remains unclear. In the present study, KCNQ1OT1 and mothers against decapentaplegic homolog (SMAD)4 expression levels were upregulated in human cataract lens posterior capsular samples and in transforming growth factor (TGF)‑β2‑treated SRA01/04 cells, as demonstrated by reverse transcription‑quantitative polymerase chain reaction, immunohistochemical staining and western blot analyses. A further loss of function test revealed that suppression of KCNQ1OT1 inhibited the proliferation and EMT of TGF‑β2‑treated SRA01/04 cells. Additionally, the present study reported that increase and decrease of KCNQ1OT1 regulated SMAD4 expression, which indicated that SMAD4 may be a downstream gene of KCNQ1OT1. Finally, a constructed SMAD4 RNA interference experiment confirmed that the function of KCNQ1OT1 was to act on LEC proliferation and EMT, and this was achieved via the SMAD4 signaling pathway. The findings of the present study may provide a novel target for molecular therapy of cataracts disease.

Statins are widely used in patients with cardiovascular diseases. A considerable number of previous studies revealed that the intracellular signaling of transforming growth factor (TGF)‑β1 mediated the development of cardiomyocyte hypertrophy and interstitial fibrosis. However, whether statins can ameliorate ventricular remodeling in post‑myocardial infarction via the TGF‑β1 signaling pathway remains to be rigorously tested. The left anterior descending artery was ligated to induce a rat model of myocardial infarction. The rat model of myocardial infarction was treated with simvastatin through gastric gavage (10, 20 or 40 mg kg‑1·d‑1). All rats were sacrificed on day 28 after the myocardial infarction operation. The results revealed that simvastatin significantly improved the hemodynamic indexes, left ventricular mass index, the myocardial tissue structure, the cardiomyocyte cross‑sectional area and the collagen volume fraction, and also showed that the levels of TGF‑β1, TGF‑activated kinase (TAK)1 and drosophila mothers against decapentaplegic (Smad)3 were significantly reduced following treatment with simvastatin, while the levels of Smad7 in the simvastatin treatment groups were markedly increased. The results of the present study suggested that statins ameliorated ventricular remodeling in post‑myocardial infarction rats via the TGF‑β1 signaling pathway, which provided a novel explanation for the pleiotropic effects of statins that benefit the cardiovascular system.

Full‑thickness and large area defects of articular cartilage are unable to completely repair themselves and require surgical intervention, including microfracture, autologous or allogeneic osteochondral grafts, and autologous chondrocyte implantation. A large proportion of regenerative cartilage exists as fibrocartilage, which is unable to withstand impacts in the same way as native hyaline cartilage, owing to excess synthesis of type I collagen in the matrix. The present study demonstrated that low‑dose halofuginone (HF), a plant alkaloid isolated from Dichroa febrifuga, may inhibit the synthesis of type I collagen without influencing type II collagen in the extracellular matrix of chondrocytes. In addition, HF was revealed to inhibit the phosphorylation of mothers against decapentaplegic homolog (Smad)2/3 and promoted Smad7 expression, as well as decrease the synthesis of type I collagen synthesis. Results from the present study indicated that HF treatment suppressed the synthesis of type I collagen by inhibiting the transforming growth factor‑β signaling pathway in chondrocytes. These results may provide an alternative solution to the problems associated with fibrocartilage, and convert fibrocartilage into hyaline cartilage at the mid‑early stages of cartilage regeneration. HF may additionally be used to improve monolayer expansion or 3D cultures of seed cells for the tissue engineering of cartilage.

Jia-Shen decoction (JSD) is a traditional Chinese medicine, which is used widely to treat chronic heart failure. However, the underlying mechanism remains to be elucidated. The present study aimed to investigate the mechanism underlying the effects of JSD on cardiac fibroblast (CF) proliferation and differentiation. The CFs were obtained from the hearts of neonatal (1‑3‑day old) Sprague‑Dawley rats and treated with JSD-medicated serum (JSDS) with or without angiotensin II (Ang II). Cell proliferation was assessed using Cell Counting Kit‑8 reagent. In addition, the mRNA expression levels of transforming growth factor‑β1 (TGF‑β1) and phosphorylated small mothers against decapentaplegic (p‑Smad)2/3 and their protein expression levels were analyzed. CF proliferation was significantly increased in the Ang II‑treated group, compared with the control group (P<0.05). The expression levels of collagen, α‑smooth muscle actin, TGF‑β1 and p‑Smad2/3 were also increased in the Ang II‑treated group (P<0.05). Following JSDS treatment, the increased levels of collagen and cell proliferation were inhibited, and the increased expression levels of p‑Smad2 and p‑Smad3 were also inhibited (P<0.05). These data suggested that JSDS may inhibit CF proliferation via attenuating the TGF‑β1/Smad signaling pathway.

Lung cancer is a complex disease involving multiple genetic and phenotypic alterations. As a histone modification enzyme, protein‑arginine deiminase type‑4 (PADI4) and its downstream signaling have been studied in the progression of a variety of types of human cancer, but data on PADI4‑mediated posttranslational modification in lung cancer are lacking. The aim of present study was to evaluate the expression of PADI4 and its associated molecular signaling in lung cancer metastasis. The results of the present study indicated that PADI4 was overexpressed in lung cancer cells, while knockdown of PADI4 could lead to attenuation of the lung cancer cell invasion and migration phenotype, which was further verified by determining the epithelial‑mesenchymal transition (EMT) marker proteins. Additionally, it was demonstrated that stable knockdown of PADI4 in A549 lung cancer cells resulted in a striking reduction of the EMT‑associated Snail1/mothers against decapentaplegic homolog 3/4 transcriptional complex, which was consistent with alterations in migratory and invasive phenotypes of A549 lung cancer cells. Therefore, PADI4‑mediated EMT transition is proposed to represent a novel mechanism underlying the epigenetic and phenotypic alterations in lung cancer cells, and the PADI4 associated signaling pathway may be a therapeutic target for treating lung cancer in a clinical setting.