Embryonic exposure to aluminum chloride blocks the onset of spermatogenesis through disturbing the dynamics of testicular tight junctions via upregulating Slc25a5 in offspring.

Studies have revealed neurotoxicity, hepatotoxicity, and developmental and reproductive toxicity in mice exposed to aluminum. However, relatively few studies have been conducted to clarify the mechanism underlying the impact of embryonic exposure to aluminum on the development of the male reproductive system in offspring. Pregnant mice were administered aluminum chloride (AlCl3) by gavage from day 12.5 of gestation until birth. Our findings demonstrated that embryonic exposure to AlCl3 disrupted testicular development and spermatogenesis by impairing testicular architecture, reducing sperm count, and upregulating the expression of tight junction (TJ) protein between Sertoli cells (SCs). Further in vitro studies revealed that treatment with AlCl3 stabilized TJ proteins Occludin and ZO-1 expression by inhibiting ERK signaling pathway activation, thereby upregulating Slc25a5 expression which induced ATP production leading to disruption of cytoskeletal protein homeostasis. Therefore, the study provided a new mechanistic insight into how AlCl3 exposure interfered with testicular development and spermatogenesis while suggesting that Slc25a5 might be a target affected by AlCl3 influencing cell metabolism.

Uncovering the ceRNA network and DNA methylation associated with gene expression in nasopharyngeal carcinoma.

OBJECTIVE: This study aimed to uncover abnormally expressed genes regulated by competitive endogenous RNA (ceRNA) and DNA methylation nasopharyngeal carcinoma and to validate the role of lncRNAs in the ceRNA network on nasopharyngeal carcinoma progression. METHODS: Based on the GSE64634 (mRNA), GSE32960 (miRNA), GSE95166 (lncRNA), and GSE126683 (lncRNA) datasets, we screened differentially expressed mRNAs, miRNAs and lncRNAs in nasopharyngeal carcinoma. A ceRNA network was subsequently constructed. Differentially methylated genes were screened using the GSE62336 dataset. The abnormally expressed genes regulated by both the ceRNA network and DNA methylation were identified. In the ceRNA network, the expression of RP11-545G3.1 lncRNA was validated in nasopharyngeal carcinoma tissues and cells by RT-qPCR. After a knockdown of RP11-545G3.1, the viability, migration, and invasion of CNE-2 and NP69 cells was assessed by CCK-8, wound healing and Transwell assays. RESULTS: This study identified abnormally expressed mRNAs, miRNAs and lncRNAs in nasopharyngeal carcinoma tissues. A ceRNA network was constructed, which contained three lncRNAs, 15 miRNAs and 129 mRNAs. Among the nodes in the PPI network based on the mRNAs in the ceRNA network, HMGA1 was assessed in relation to the overall and disease-free survival of nasopharyngeal carcinoma. We screened two up-regulated genes regulated by the ceRNA network and hypomethylation and 26 down-regulated genes regulated by the ceRNA network and hypermethylation. RP11-545G3.1 was highly expressed in the nasopharyngeal carcinoma tissues and cells. Moreover, the knockdown of RP11-545G3.1 reduced the viability, migration, and invasion of CNE-2 and NP69 cells. CONCLUSION: Our findings uncovered the epigenetic regulation in nasopharyngeal carcinoma and identified the implications of RP11-545G3.1 on the progression of nasopharyngeal carcinoma.

Diallyl Trisulfide, a Biologically Active Component of Garlic Essential Oil, Decreases Male Fertility in Sitotroga cerealella by Impairing Dimorphic Spermatogenesis, Sperm Motility and Lipid Homeostasis.

Diallyl trisulfide (DAT) is a biologically active component of garlic essential oil and exhibits multi-targeted activity against many organisms. The current study tested the capacity of DAT to decrease the male fertility of Sitotroga cerealella. The effects on testis morphology, sperm number, motility, and lipid homeostasis were observed in adult males fumigated with DAT at a dose of 0.01 µL/L in air. The results indicated that the DAT significantly decreased the dimorphic sperm number. Meanwhile, the ultrastructural analysis of the sperm showed that the DAT caused malformed and aberrant structures of mitochondrial derivatives of dimorphic sperm. Additionally, the lipid homeostasis and ATP contents in the male adults were significantly decreased after treatment. Moreover, the total sperm motility was reduced, while the wave-propagation velocity, amplitude, frequency, and wavelength were significantly decreased compared with the controls. Overall, this study reported, for the first time, that DAT impairs energy metabolism, inhibits dimorphic spermatogenesis, and decreases sperm motility, while these abnormalities in sperm lead to adult-male infertility.

Environmentally relevant perinatal exposure to DBP accelerated spermatogenesis by promoting the glycolipid metabolism of Sertoli cells in male offspring mice.

Since Sertoli cells (SCs) play an essential role in providing energy for spermatogenesis, the present study aimed to investigate the effects of maternal exposure to plasticizer Dibutyl phthalate (DBP) on the onset of spermatogenesis in male offspring through the metabolism pathway as well as the underlying molecular mechanism. Here, pregnant mice were treated with 0 (control), 50, 250, or 500 mg/kg/day DBP in 1 mL/kg corn oil administered daily by oral gavage from gestation day (GD) 12.5 to parturition. The in vivo results showed that 50 mg/kg/day DBP exposure could promote the expression of glucose metabolism-related proteins (GLUT3, LDHA, and MCT4) in the testis of 22 days male offspring. The in vitro results demonstrated that 0.1 mM monobutyl phthalate (MBP, the active metabolite of DBP) promoted the lactate production, glucose consumption, and glycolytic flux of immature SCs, which was paralleled by the upregulated expression of glucose metabolism-related proteins (GLUT1, GLUT3, LDHA, and MCT4). On the other hand, DBP/MBP increased fatty acid (FA) uptake, FA ß-oxidation, and ATP production by promoting the expression of CD36 in immature SCs, which might accelerate the maturity of SCs to support the onset of spermatogenesis. Therefore, our findings provided a new perspective on glycolipid metabolism to explain prenatal DBP exposure leading to earlier onset of spermatogenesis in male offspring mice.

Novel compound heterozygous variants of DNAH17 in a Chinese infertile man with multiple morphological abnormalities of sperm flagella.

Multiple morphological abnormalities of the sperm flagellum (MMAF) have been reported to be an important cause of male infertility and reflect a heterogeneous genetic disorder. Previous studies have identified dozens of candidate pathogenic genes for MMAF, but the aetiology in approximately 50% of cases remains unexplained. The present study aimed to identify novel potentially pathogenic gene variants of MMAF. A Chinese family with a 32-year-old infertile proband presenting with MMAF was recruited, and sperm morphology of the patient was examined by Papanicolaou staining. Whole exome sequencing was performed on the proband and Sanger sequencing was used to identify genetic variants in the family. The frequencies of variants were assessed using public databases and the effects on protein structure and function were predicted by online bioinformatics tools. The patient exhibited asthenozoospermia and a MMAF phenotype. Novel compound heterozygous variants (c.5368C > T, p.R1790C and c.13183C > T, p.R4395W) of the DNAH17 gene were identified in the patient, and showed autosomal recessive inheritance in this family. These variants were very rare in the GnomAD database. The two mutated amino acids were located in a highly conserved region of the DNAH17 protein. In silico analysis revealed that the compound heterozygous variants may compromise the function of DNAH17. Our findings expand upon the spectrum of pathogenic DNAH17 variants that are responsible for MMAF, and provide new knowledge for genetic counselling of male infertility due to MMAF.

Dendrobium nobile-derived polysaccharides ameliorate spermatogenic disorders in mice with streptozotocin-induced diabetes through regulation of the glycolytic pathway.

Dysfunction of spermatogenesis is a major complication of diabetes mellitus (DM). This study characterized the protective effects of Dendrobium nobile-derived polysaccharides (DNP) against spermatogenetic dysfunction in mice with streptozotocin (STZ)-induced diabetes. The diabetic mice had lower body and testicular mass, and fewer spermatozoa with a higher incidence of malformation. The testicular histology showed disordered narrow seminiferous tubules covering a smaller area, and fewer spermatogenic cells. Moreover, the qRT-PCR analysis indicated that DM was associated with high expression of the pro-apoptotic factor Bax and low expression of the anti-apoptotic factor Bcl-2 in the testes. The qRT-PCR and immunohistochemical analysis clarified that DM was also associated with low testicular expression of the Sertoli cell (SC) markers GATA-4, WT1, and vimentin, and genes encoding the glycolytic rate-limiting enzymes LDHA, PKM2, and HK2. DNP treatment increased the body and testicular masses, sperm count, and number of spermatogenic cells of the mice, and reduced the proportion of abnormal sperm. DNP also reduced the expression of Bax, and increased that of Bcl-2, GATA-4, WT1, vimentin, LDHA, PKM2, and HK2, in the testes of the diabetic mice. Thus, DNP protects against spermatogenic dysfunction in diabetic mice by inhibiting apoptosis and activating the glycolytic pathway in their testes.

Calycosin inhibits breast cancer cell migration and invasion by suppressing EMT via BATF/TGF-ß1.

In this study, we investigated the effects of calycosin on breast cancer cell progression and their underlying mechanisms. Calycosin dose- and time-dependently inhibited proliferation, migration, and invasion by T47D and MCF-7 breast cancer cells by downregulating basic leucine zipper ATF-like transcription factor (BATF) expression. Moreover, BATF promoted breast cancer cell migration and invasiveness by increasing TGFß1 mRNA and protein levels. Bioinformatics analysis, dual luciferase reporter assays, and chromatin immunoprecipitation assays confirmed the presence of BATF-binding sites in the promoter sequence of TGFß1 gene. Calycosin treatment inhibited epithelial-mesenchymal transition (EMT) of breast cancer cells by significantly increasing E-cadherin levels and decreasing N-cadherin, Vimentin, CD147, MMP-2, and MMP-9 levels through downregulation of BATF and TGFß1. TGFß1 knockdown reduced the migration and invasiveness of BATF-overexpressing breast cancer cells, whereas incubation with TGFß1 enhanced the migration and invasiveness of calycosin-treated breast cancer cells. Our findings demonstrated that calycosin inhibited EMT and progression of breast cancer cells by suppressing BATF/TGFß1 signaling. This suggests calycosin would be a promising therapeutic option for breast cancer patients.

LncRNA HOTAIR regulates the expression of E-cadherin to affect nasopharyngeal carcinoma progression by recruiting histone methylase EZH2 to mediate H3K27 trimethylation.

BACKGROUND/AIM: There has been increasing evidence for the function of long non-coding RNA (lncRNA) in nasopharyngeal carcinoma (NPC). We aim to delve into the position of lncRNA HOX antisense intergenic RNA (HOTAIR), together with enhancer of zeste homolog 2 (EZH2), E-cadherin and trimethylation of lysine 27 on histone H3 (H3K27me3) in NPC. METHODS: HOTAIR, EZH2, and E-cadherin expression in NPC tissues and cells were tested. NPC cell biological functions were examined through gain-of and loss-of function assays. The mechanism of lncRNA HOTAIR/E-cadherin/EZH2/H3K27 axis in NPC was decoded. RESULTS: LncRNA HOTAIR and EZH2 were highly expressed in NPC, and E-cadherin was lowly expressed. Down-regulation of HOTAIR or EZH2 inhibited NPC cell progression and tumor growth. HOTAIR recruited histone methylase EZH2 to mediate trimethylation of H3K27 and regulated E-cadherin expression. CONCLUSION: HOTAIR inhibits E-cadherin by stimulating the trimethylation of H3K27 to promote NPC cell progression through recruiting histone methylase EZH2.

FASCIN regulates actin assembly for spindle movement and polar body extrusion in mouse oocyte meiosis.

During mouse oocyte meiotic maturation, actin filaments play multiple roles in meiosis such as spindle migration and cytokinesis. FASCIN is shown to be an actin-binding and bundling protein, making actin filaments tightly packed and parallel-aligned, and FASCIN is involved in several cellular processes like adhesion and migration. FASCIN is also a potential prognostic biomarker and therapeutic target for the treatment of metastatic disease. However, little is known about the functions of FASCIN in oocyte meiosis. In the present study, we knocked down the expression of FASCIN, and our results showed that FASCIN was essential for oocyte maturation. FASCIN was all expressed in the different stages of oocyte meiosis, and it mainly localized at the cortex of oocytes from the GV stage to the MII stage and showed a similar localization pattern with actin and DAAM1. Depletion of FASCIN affected the extrusion of the first polar body, and we also observed that some oocytes extruded from the large polar bodies. This might have resulted from the defects of actin assembly, which further affected the meiotic spindle positioning. In addition, we showed that inhibition of PKC activity decreased FASCIN expression, indicating that FASCIN might be regulated by PKC. Taken together, our results provided evidence for the important role of FASCIN on actin filaments for spindle migration and polar body extrusion in mouse oocyte meiosis.

Effects of diallyl trisulfide, an active substance from garlic essential oil, on structural chemistry of chitin in Sitotroga cerealella (Lepidoptera: Gelechiidae).

The environmental pollution, evolution of resistance, and risks to human and aquatic animal health associated with pesticide application have attracted much attention globally. Herein, we tested the capacity of diallyl trisulfide (DAT) from garlic essential oil to control the destructive stored-product pest, Sitotroga cerealella. The effects of DAT on the total content of cuticular chitin and structure of adults S. cerealella were evaluated. This study was the first to investigate changes in chitin structure in adults due to exposure to DAT through Fourier-transform infrared spectroscopy, thermogravimetric analysis, X-ray diffraction, and differential scanning calorimetry. The results of these analyses revealed that the cuticular chitin content of pests decreased after DAT treatment. DAT treatment also reduced thermal stability and crystallinity of chitin. These findings indicate that DAT is a potent biopesticide that is active against the moth, and establishes the basis for its use as an IPM and alternative to chitin synthesis inhibitors.

Effects of Diallyl Trisulfide, an Active Substance from Garlic Essential Oil, on Energy Metabolism in Male Moth Sitotroga cerealella (Olivier).

This study investigated the effects of diallyl trisulfide (DAT), an active substance from garlic essential oil, on the metabolism of the main energy substances of pre- and postmating males of Sitotroga cerealella. Males at 12 h postemergence were fumigated with DAT at a concentration (LC10 = 0.010 µL/L) in a glass jar for 7 h. The main energy metabolites from pre- and postmating males were determined, including protein, triglyceride, glycogen, total soluble sugar, trehalose, and trehalase. The contents of total protein and total soluble sugar and the trehalase activity of premating males were significantly increased following DAT treatment, whereas the contents of protein from the accessory gland, triglyceride, glycogen, and trehalose were significantly decreased after treatment. Additionally, after mating, the total protein and soluble sugar contents were significantly increased and the glycogen content was significantly decreased in the treatment group relative to the levels in controls, but there was no significant difference observed in triglyceride, accessory gland proteins, trehalose content, or trehalase activity between the treatment and control groups. Furthermore, the changes in the main energy substances between pre- and postmating in males after the DAT treatment (∆DAT) were smaller than those in the control group (∆CK). This result indicated that DAT can accelerate the rate of metabolism in males at LC10, leading to the accumulation of greater levels of total soluble sugar to support life activities and to the increased synthesis of proteins to resist an adverse environment.

Alteration in the sensitivity to crizotinib by Na+/H+ exchanger regulatory factor 1 is dependent to its subcellular localization in ALK-positive lung cancers.

BACKGROUND: Na+/H+ exchanger regulatory factor 1 (NHERF1) is an important scaffold protein participates in the modulation of a variety of intracellular signal pathways. NHERF1 was able to enhance the effects of chemo-drugs in breast and cervical cancer cells. Anaplastic lymphoma kinase (ALK) fusion mutations are validated molecules targeted therapy in lung cancers, where crizotinib can be used as the specific inhibitor to suppress tumor progression. However, due to the less frequent occurrence of ALK mutations and the complexity for factors to determine drug responses, the genes that could alter crizotinib sensitivity are unclear. METHODS: Both ALK-translocated and ALK-negative lung adenocarcinoma specimens in tissue sections were collected for immunohistochemistry. The possible mechanisms of NHERF1 and its role in the cell sensitivity to crizotinib were investigated using an ALK-positive and crizotinib-sensitive lung adenocarcinoma cell line H3122. Either a NHERF1 overexpression vector or agents for NHERF1 knockdown was used for crizotinib sensitivity measures, in association with cell viability and apoptosis assays. RESULTS: The expression level of NHERF1 in ALK-translocated NSCLC was significantly higher than that in other lung cancer tissues. NHERF1 expression in ALK positive lung cancer cells was regulated by ALK activities, and was in return able to alter the sensitivity to crizotinib. The function of NHERF1 to influence crizotinib sensitivity was depending on its subcellular distribution in cytosol instead of its nucleus localized form. CONCLUSION: Ectopically overexpressed NHERF1 could be a functional protein for consideration to suppress lung cancers. The determination of NHERF1 levels in ALK positive NSCLC tissues might be useful to predict crizotinib resistance, especially by distinguishing cytosolic or nuclear localized NHERF1 for the overexpressed molecules.

Exosomal lncRNA HNF1A-AS1 affects cisplatin resistance in cervical cancer cells through regulating microRNA-34b/TUFT1 axis.

BACKGROUND: There is growing evidence of the role of long non-coding RNAs (lncRNAs) in cervical cancer (CC). The objective was to discuss whether exosomal lncRNA HNF1A-AS1 impacted drug resistance in CC via binding to microRNA-34b (miR-34b) and regulating TUFT1 expression. METHODS: The expression of HNF1A-AS1 in normal cervical epithelial cells, cisplatin (DDP)-sensitive cell line (HeLa/S) and DDP-resistant cell line (HeLa/DDP) cells were detected. HeLa/S and HeLa/DDP cells were interfered with HNF1A-AS1 to determine IC50, proliferation, colony formation and apoptosis of CC cells. The exosomes were isolated and identified. Subcellular localization of HNF1A-AS1, expression of miR-34b and TUFT1 in receptor cells were also verified. The binding site between HNF1A-AS1 and miR-34b, together with miR-34b and TUFT1 were confirmed. Tumorigenic ability of cells in nude mice was also detected. RESULTS: HNF1A-AS1 was upregulated in DDP-resistant cell line HeLa/DDP. Silencing HNF1A-AS1 suppressed CC cell proliferation and promoted its apoptosis. HNF1A-AS1 was found to act as a competing endogenous RNA (ceRNA) of miR-34b to promote the expression of TUFT1. Exosomes shuttled HNF1A-AS1 promoted the proliferation and drug resistance of CC cells and inhibited their apoptosis by upregulating the expression of TUFT1 and downregulating miR-34b. Furthermore, suppressed exosomal HNF1A-AS1 in combination with DDP inhibited tumor growth in nude mice. CONCLUSION: Our study provides evidence that CC-secreted exosomes carrying HNF1A-AS1 as a ceRNA of miR-34b to promote the expression of TUFT1, thereby promoting the DDP resistance in CC cells.

Impact of RTN4 gene polymorphism and its plasma level on susceptibility to nasopharyngeal carcinoma: A case-control study.

The RTN4 gene plays a role in the development and progression of cancer. This case-control study aimed to investigate the association between the RTN4 gene polymorphism and its plasma level with the risk of nasopharyngeal carcinoma (NPC) in a Chinese population.RTN4 gene polymorphisms (rs2920891, rs17046583, rs117465650, rs10496040, and rs2588519) in 220 patients with NPC and 300 healthy controls were analyzed using Snapshot single-nucleotide polymorphism genotyping assays. The plasma level of RTN4 was measured using the enzyme-linked immunosorbent assay.The allele frequencies of RTN4 gene polymorphisms showed no significant difference between the patients and controls (P > .05). Nevertheless, the rs2920891 polymorphism in a dominant model (A/C+C/C) and codominant model (A/C) was significantly associated with the susceptibility to NPC (P = .017, odds ratio [OR] = 1.54, 95% confidence interval [CI] = 1.08-2.21 and P = .034, OR = 1.64, 95% CI = 1.13-2.38, respectively). The plasma level of RTN4 was significantly higher in patients with NPC in comparison with the controls (P < .001). Furthermore, we observed that patients with NPC carrying the rs2920891 A/C+C/C genotype had a higher RTN4 level than those carrying the A/A genotype (P < .001).Our findings indicated that the rs2920891 polymorphism may be associated with increased susceptibility to NPC, possibly by increasing plasma RTN4.

[Progress in epigenetic modification of mRNA and the function of m6A modification].

Messenger RNA (mRNA) can be modified by more than 100 chemical modifications. Among these modifications, N6-methyladenosine (m6A) is one of the most prevalent modifications. During the processes of cells differentiation, embryo development or stress, m6A can be modified on key mRNAs and regulate the progress of cells through modulating mRNA metabolism and translation. Other mRNA modifications, including N1-methyladenosine (m¹A), 5-methylcytosine (m5C) and pseudouridine, together with m6A form the epitranscriptome of mRNA that accurately modulate the mRNA translation. Here we review the types and characteristic of mRNA epigenetic modifications, especially the recent progresses of the function of m6A, we also expect the main research direction of m6A epigenetic modification in the future.

Genetic polymorphisms in interleukin 13 gene with the susceptibility to nasopharyngeal carcinoma in a Chinese population.

Although inflammation is emerging as a candidate risk factor in tumorigenesis of nasopharyngeal carcinoma (NPC). In particular, Interleukin (IL) 13 involved inflammatory diseases and cancers. Single nucleotide polymorphisms in IL-13 have been associated with multiple cancers. The study analyzed genetic polymorphisms in IL-13 aiming to investigate its' potential susceptibility with the NPC. The genotyping of polymorphisms (rs20541, rs1295687 and rs2069744) was examined by Snapshot SNP and DNA sequencing. All SNPs were within Hardy-Weinberg equilibrium and each appeared in three genotypes in NPC and controls. Adjusted logistic regression showed that the TT genotype of rs20541 increased the risk of lymph node metastasis (TT vs. CC: OR = 2.87, 95%CI, 1.33-6.18, P = 0.007). CT/CC genotypes were associated with the decreased the risk of lymph node metastasis in NPC (CT/CC vs. TT: OR = 0.32, 95%CI, 0.16-0.65, P = 0.002). The concentration of IL-13 was significantly elevated in NPC patients compared with controls (P = 0.012). Moreover, significant differences were detected in the T-C-T haplotype distribution between NPC patients and controls (OR = 2.47, 95%CI, 1.06-5.78, P = 0.031). Our results, the first report, provide evidence that rs20541 polymorphisms may affect the lymph node metastasis of NPC patients in Chinese population.

Lycium barbarum polysaccharide prevents cisplatin-induced MLTC-1 cell apoptosis and autophagy via regulating endoplasmic reticulum stress pathway.

BACKGROUND: Lycium barbarum polysaccharide (LBP) has been reported to contribute to the recovery of male hypogonadism and infertility. AIM: The aim of current study was to investigate the underlying mechanisms of LBP on male infertility recovery. METHODS: Recently, it is reported that cell apoptosis mediated by endoplasmic reticulum stress (ERS) was distinguished from that mediated by death reporters and mitochondria pathway, which could induce cell apoptosis independently. The possible signaling mechanisms were investigated using diversified molecular biology techniques, such as flow cytometry, western blotting, and immunofluorescence. RESULTS: In this study, we found that LBP protected Leydig MLTC-1 cells against cisplatin (DDP) by regulating ERS-mediated signal pathway, which was evidenced by downregulation of phosphorylation PERK, phosphorylation of eukaryotic translation-initiation factor 2α and activating transcription factor 4. Meanwhile, LBP decreased DDP-induced MLTC-1 cell apoptosis via reducing ERS apoptosis-relative proteins caspase 3, caspase 7, and caspase 12. In addition, the result of monodansylcadaverine staining indicated that LBP significantly inhibited DDP-induced autophagosome formation in MLTC-1 cells. Moreover, immunofluorescences and Western blot assays demonstrated that LBP reversed DDP-induced LC3II and Atg5 upregulation in MLTC-1 cells. Finally, the data of enzyme-linked immunosorbent assay showed that LBP markedly recovered MLTC-1 cells testosterone level even in the presence of DDP. CONCLUSION: Thus, we suggest that LBP protected MLTC-1 cells against DDP via regulation of ERS-mediated apoptosis and autophagy.

NHERF1 Suppresses Lung Cancer Cell Migration by Regulation of Epithelial-Mesenchymal Transition.

BACKGROUND/AIM: Na(+)/H(+) exchanger regulatory factor 1 (NHERF1) has been reported to interact with many cancer-related proteins and plays an important role in cancer progression. However, little is known about the biological functions of NHERF1 in lung cancer cells. The aim of the current study was to explore whether NHERF1 is involved in transforming growth factor (TGF)-ß1-induced epithelial-mesenchymal transition (EMT) in non-small-cell lung cancer cells. MATERIALS AND METHODS: The expression of NHERF1 and EMT-associated markers including E-cadherin, N-cadherin, snail family transcriptional repressor 1 (SNAI1) and snail family transcriptional repressor 2 (SLUG) were analyzed by reverse transcription polymerase chain reaction (RT-PCR) and western blotting. The migratory properties of cells were assessed using a wound-healing assay. RESULTS: TGF-ß1-induced a pro-migratory response in the A549 lung cancer cell line, that was consistently associated with corresponding changes in the expression levels of EMT-related genes. The expression of NHERF1 significantly decreased in the TGF-ß1-induced A549 cells. Overexpression of NHERF1 significantly inhibited the migratory ability of cells and reversed the TGF-ß1-induced mesenchymal phenotype of A549 cells. CONCLUSION: These data showed an important role of NHERF1 in the EMT of non-small-cell lung cancer cells, as well as migration.