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Background: As a component of the nucleosome remodeling and deacetylating (NuRD) complex, metastasis‐associated protein 1 (MTA1) has been reported to be abundant in male reproductive system and might participate in spermatogenesis and sperm maturation, whereas the precise functional role of MTA1 in these processes is still undetermined. Objective: To investigate the effect and potential function of MTA1 in male fertility. Materials and methods: Mta1 knockout mice (Mta1−/−) were employed to detect their reproductive phenotype. The pH value of Mta1−/− epididymal luminal fluid was measured, and the potential mechanism of MTA1 involved in regulating luminal acidification was detected in vivo and in vitro. A vasectomy model with abnormal pH of epididymal lumen was established to further detect the effect of MTA1 on epididymal luminal microenvironment. Results: Mta1−/− mice were fertile without any detectable defects in spermatogenesis or sperm motility while the deficiency of MTA1 could acidify the initial segment of epididymis to a certain extent. MTA1 could interact with estrogen receptor alpha (ERα) and inhibit the transcription of ERα target gene, hydrogen exchanger 3 (NHE3), and ultimately affect the epididymal luminal milieu. After vasectomy, the Mta1−/− mice presented a more acidic epididymal lumen which was closer to the normal state compared to the wild‐type model. Discussion and conclusion: MTA1 is dispensable for male fertility in mice, but plays a potentially important function in regulating luminal acidification of the epididymis. [ABSTRACT FROM AUTHOR]

Cancer remains a significant global health challenge, prompting exploration into alternative treatments such as those derived from natural compounds found in traditional medicine. Recent research has underscored the role of proteins like Focal Adhesion Kinase (FAK), Vascular Endothelial Growth Factor (VEGF), and Metastasis-Associated Protein 1 (MTA1) in driving cancer cell proliferation and survival. Here, we investigated the potential of a single molecule to modulate these key proteins involved in metastasis, offering a promising avenue for cancer therapy. Terminalia elliptica, commonly known as Asna, possesses a diverse range of medicinal properties, including antimicrobial, anti-inflammatory, anticancer, antidiabetic, antiaging, hepatoprotective, antioxidant, and neuroprotective activities. Our study aimed to explore the anticancer potential of Terminalia elliptica by identifying bioactive compounds capable of targeting FAK, VEGF, and MTA1 to impede cancer metastasis. Through in silico analysis, we conducted network analysis using Cytoscape to assess the significance of these bioactive compounds in the inhibition of signaling pathways driving metastasis. The utilization of these bioactives as potential candidates for targeted therapy of VEGF, FAK, and MTA1 regulated pathways was preliminarily assessed by Molecular Docking and MD Simulation. Our findings revealed that phytobioactives namely, Chebulinic Acid of Terminalia elliptica, exhibited notable binding affinity and interaction with FAK, and Chebulagic Acid with VEGF, and MTA1. This discovery holds promise as a novel therapeutic approach for combating cancer, offering potential benefits in cancer treatment and management. [ABSTRACT FROM AUTHOR]

Cancer remains a significant global health challenge, prompting exploration into alternative treatments such as those derived from natural compounds found in traditional medicine. Recent research has underscored the role of proteins like Focal Adhesion Kinase (FAK), Vascular Endothelial Growth Factor (VEGF), and Metastasis-Associated Protein 1 (MTA1) in driving cancer cell proliferation and survival. Here, we investigated the potential of a single molecule to modulate these key proteins involved in metastasis, offering a promising avenue for cancer therapy. Terminalia elliptica, commonly known as Asna, possesses a diverse range of medicinal properties, including antimicrobial, anti-inflammatory, anticancer, antidiabetic, antiaging, hepatoprotective, antioxidant, and neuroprotective activities. Our study aimed to explore the anticancer potential of Terminalia elliptica by identifying bioactive compounds capable of targeting FAK, VEGF, and MTA1 to impede cancer metastasis. Through in silico analysis, we conducted network analysis using Cytoscape to assess the significance of these bioactive compounds in the inhibition of signaling pathways driving metastasis. The utilization of these bioactives as potential candidates for targeted therapy of VEGF, FAK, and MTA1 regulated pathways was preliminarily assessed by Molecular Docking and MD Simulation. Our findings revealed that phytobioactives namely, Chebulinic Acid of Terminalia elliptica, exhibited notable binding affinity and interaction with FAK, and Chebulagic Acid with VEGF, and MTA1. This discovery holds promise as a novel therapeutic approach for combating cancer, offering potential benefits in cancer treatment and management.

Abstract Background The effect of circular RNAs (circRNAs) is widely studied in various human cancers, including breast cancer (BC). Herein, circUSPL1 has been recognized as a new regulator for BC progression. However, the detailed biological function and molecular mechanism of circUSPL1 in BC remain vague. Methods The expression level of circUSPL1, miR‐1296‐5p and metastasis associated 1 (MTA1) was examined by quantitative reverse transcription PCR. BC cell proliferation, migration, invasion, apoptosis and aerobic glycolysis were analyzed by colony formation assay, 5‐ethynyl‐2′‐deoxyuridine assay, wound healing assay, transwell assay, flow cytometry and glycolysis corresponding kits, respectively. The protein level of Bcl‐2, Bax, HK2, GLUT1 and MTA1 was evaluated by western blot analysis. The relationship of miR‐1296‐5p and circUSPL1 or MTA1 was affirmed using dual‐luciferase reporter or RIP assays. A murine xenograft model was conducted to analyze the tumor growth in vivo. Results CircUSPL1 and MTA1 expression level was increased, but miR‐1296‐5p was particularly reduced in BC tissues and cells. CircUSPL1 deficiency significantly inhibited BC cell proliferation, migration, invasion, glycolysis, and promoted cell apoptosis. In addition, circUSPL1 directly targeted miR‐1296‐5p, and downregulation of miR‐1296‐5p eliminated the inhibitory action of circUSPL1 knockdown. Additionally, overexpression of miR‐1296‐5p repressed cell malignant properties, while the suppressive effects were overturned by MTA1 elevation. Lastly, silencing of circUSPL1 inhibited tumor growth by sponging miR‐1296‐5p and regulating MTA1. Conclusion CircUSPL1 deficiency repressed BC cell malignant phenotypes through reducing MTA1 via targeting miR‐1296‐5p, which might provide a theoretical basis for BC treatment.

We previously identified a cell cycle-dependent periodic subcellular distribution of cancer metastasis-associated antigen 1 (MTA1) and unraveled a novel role of MTA1 in inhibiting spindle damage-induced spindle assembly checkpoint (SAC) activation in cancer cells. However, the more detailed subcellular localization of MTA1 in mitotic cells and its copartner in SAC regulation in cancer cells are still poorly understood. Here, through immunofluorescent colocalization analysis of MTA1 and alpha-tubulin in mitotic cancer cells, we reveal that MTA1 is dynamically localized to the spindle apparatus throughout the entire mitotic process. We also demonstrated a reversible upregulation of MTA1 expression upon spindle damage-induced SAC activation, and time-lapse imaging assays indicated that MTA1 silencing delayed the mitotic metaphase-anaphase transition in cancer cells. Further investigation revealed that MTA1 interacts and colocalizes with Translocated Promoter Region (TPR) on spindle microtubules in mitotic cells, and this interaction is attenuated on SAC activation. TPR is well-implicated in SAC regulation via binding the MAD1-MAD2 complex, however, no interactions between MTA1 and MAD1 or MAD2 were detected in our coimmunoprecipitation (co-IP) assays, suggesting that the MTA1-TPR may represent a distinct SAC-associated complex separate from the previously reported TPR-MAD1/MAD2 complex. Our data provide new insights into the subcellular localization and molecular function of MTA1 in SAC regulation in cancer, and indicate that intervention of the MTA1-TPR interaction may be effective to modulate SAC and hence chromosomal instability (CIN) in tumorigenesis. • MTA1 localizes to the mitotic spindle apparatus during mitosis. • MTA1 is upregulated on spindle damage-induced SAC activation. • MTA1 silencing delays the mitotic metaphase-anaphase transition. • MTA1 interacts and colocalizes with TPR on the spindle apparatus. • MTA1-TPR interaction is weakened upon SAC activation. [ABSTRACT FROM AUTHOR]

Purpose: Vulvar cancer is the fourth most common malignancy of the female genital tract after endometrial, ovarian, and cervical carcinoma and affects mainly elderly women. In 2020 there were registered more than 17,000 deaths worldwide related to vulvar carcinoma. Data about target-based therapies and predictive biomarkers for vulva carcinomas are rare so far. The metastasis-associated gene MTA1 is a transcriptional repressor with a potential effect on cancer. Expression of MTA1 was found to be significantly enhanced in gynecological malignancies as breast or ovarian cancer tissues with advanced cancer stages and higher FIGO grading, indicating an important role of MTA1 in the progression of those tumor entities. Due to the lack of information around MTA1 and its significance regarding vulvar carcinoma, this study focuses on the expression of MTA1 in vulvar carcinoma and its correlation to clinicopathological characteristics and prognosis. Methods: A total of 157 paraffin-embedded vulvar cancer tissues were immunohistochemically stained and examined for MTA1 expression by using the immunoreactive score. Subsequently, the values were correlated with clinicopathological parameters. Results: MTA1 was found to be expressed in 94% of the patients in the cytoplasm and 91% in the nucleus. Cytoplasmatic expression of MTA1 was significantly increased in non-keratinizing squamous cell carcinoma and in vulvar carcinoma of the condylomatous type, compared to keratinizing squamous cell carcinoma and vulvar carcinoma of the verrucous type. High MTA1 expression in the nucleus was associated with advanced tumor size as well as higher FIGO grading. In addition, p16 negative vulvar carcinomas showed a higher nuclear expression of MTA1 compared to p16 positive vulvar carcinomas. Suprisingly, Kaplan–Meier analysis showed a significantly lower disease-free survival in tumor samples without a nuclear expression of MTA1. Conclusions: MTA1 was identified as a negative prognostic marker for vulvar carcinoma associated with advanced tumor stage and FIGO grading. A possible explanation could be that the antibody used for this study does not bind to a possible mutation in the C terminal region of MTA leading to negative immunohistochemical staining and this can be correlated with early recurrence in patients with vulvar carcinoma. [ABSTRACT FROM AUTHOR]

Background: The effect of circular RNAs (circRNAs) is widely studied in various human cancers, including breast cancer (BC). Herein, circUSPL1 has been recognized as a new regulator for BC progression. However, the detailed biological function and molecular mechanism of circUSPL1 in BC remain vague. Methods: The expression level of circUSPL1, miR‐1296‐5p and metastasis associated 1 (MTA1) was examined by quantitative reverse transcription PCR. BC cell proliferation, migration, invasion, apoptosis and aerobic glycolysis were analyzed by colony formation assay, 5‐ethynyl‐2′‐deoxyuridine assay, wound healing assay, transwell assay, flow cytometry and glycolysis corresponding kits, respectively. The protein level of Bcl‐2, Bax, HK2, GLUT1 and MTA1 was evaluated by western blot analysis. The relationship of miR‐1296‐5p and circUSPL1 or MTA1 was affirmed using dual‐luciferase reporter or RIP assays. A murine xenograft model was conducted to analyze the tumor growth in vivo. Results: CircUSPL1 and MTA1 expression level was increased, but miR‐1296‐5p was particularly reduced in BC tissues and cells. CircUSPL1 deficiency significantly inhibited BC cell proliferation, migration, invasion, glycolysis, and promoted cell apoptosis. In addition, circUSPL1 directly targeted miR‐1296‐5p, and downregulation of miR‐1296‐5p eliminated the inhibitory action of circUSPL1 knockdown. Additionally, overexpression of miR‐1296‐5p repressed cell malignant properties, while the suppressive effects were overturned by MTA1 elevation. Lastly, silencing of circUSPL1 inhibited tumor growth by sponging miR‐1296‐5p and regulating MTA1. Conclusion: CircUSPL1 deficiency repressed BC cell malignant phenotypes through reducing MTA1 via targeting miR‐1296‐5p, which might provide a theoretical basis for BC treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: The incidence of prostate cancer is increasing because of the aging population. Evidence suggests that diets rich in bioactive polyphenols can reduce the incidence of prostate cancer. The aim of this work was to investigate the potential of gnetin C, a compound found in the melinjo plant and commonly used in Indonesian foods, to block prostate cancer progression. To this end, we evaluated the anticancer efficacy of gnetin C-supplemented diets in a unique and adequate high-risk premalignant prostate cancer transgenic mouse model. Our results indicate that a gnetin C-supplemented diet reduces the progression of prostate cancer by reducing the proliferation of cells, inflammation, and the formation of blood vessels. The finding that a gnetin C-supplemented diet effectively blocks tumor progression in a preclinical mouse model may be exploited to initiate chemoprevention trials for novel nutritional interception for untreated patients under active surveillance. Nutritional chemoprevention is particularly suitable for prostate cancer. Gnetin C, a resveratrol dimer found abundantly in the melinjo plant (Gnetum gnemon), may possess more potent biological properties compared to other stilbenes. We examined the effects of gnetin C in a high-risk premalignant transgenic mouse model overexpressing tumor-promoting metastasis-associated protein 1 (MTA1) on the background of Pten heterozygosity (R26MTA1; Pten+/f; Pb-Cre+). Mice were fed diets supplemented with the following compounds: pterostilbene (70 mg/kg diet); gnetin C, high dose (70 mg/kg diet); and gnetin C, low dose (35 mg/kg diet). Prostate tissues were isolated after 17 weeks and examined for histopathology and molecular markers. Serum was analyzed for cytokine expression. Gnetin C-supplemented diets substantially delayed the progression of preneoplastic lesions compared to other groups. Prostate tissues from gnetin C-fed mice showed favorable histopathology, with decreased severity and number of prostatic intraepithelial neoplasia (PIN) foci, reduced proliferation, and angiogenesis. A decreased level of MTA1, concurrent with the trend of increasing phosphatase and tensin homolog expression and reduced interleukin 2 (IL-2) levels in sera, were also detected in gnetin C-fed mice. Importantly, gnetin C did not exert any visible toxicity in mice. Our findings demonstrate that a gnetin C-supplemented diet effectively blocks MTA1-promoted tumor progression activity in high-risk premalignant prostate cancer, which indicates its potential as a novel form of nutritional interception for prostate cancer chemoprevention. [ABSTRACT FROM AUTHOR]

Aging is an inevitable law of the process of life during which many physiological functions change. Brain aging is an important mechanism in the occurrence and development of degenerative diseases of the central nervous system. β-Hydroxybutyrate (BHBA) is a water-soluble, endogenous small-molecule ketone that can cross the blood-brain barrier and induce neuroprotective effects. This study aimed to investigate the effects of BHBA on D-galactose (D-gal) induced aging in mice and its underlying mechanisms using in vitro and in vivo experiments. These results indicated that D-gal-induced senescence, oxidative stress, and inflammatory responses were inhibited by BHBA, and autophagy was promoted by BHBA. Mechanistically, we explored the role of metastasis-associated antigen-1 (MTA1) in D-gal-induced damaged in HT22 cells using small interfering RNA (siRNA). The results demonstrated that the expression of MTA1 was significantly increased by BHBA, which attenuated D-gal-induced aging, oxidative stress, and inflammatory responses, and promoted autophagy through the upregulation of MTA1. In conclusion, MTA1 may be a novel target for treating aging caused by neurological damage. BHBA improves brain aging by activating the MTA1 pathway. [Display omitted] [ABSTRACT FROM AUTHOR]

Artesunate (ART) is a derivative of artemisinin and has anti-inflammatory, anti-tumor, and anti-angiogenic properties. Although ART has been implicated in osteoarthritis (OA), the mechanism needs to be further dissected. Here, we explored the effects of ART on the development of OA and the underlying mechanism using destabilization of the medial meniscus (DMM) surgical instability model. Mice with OA were developed using DMM and treated with ART. The pathological morphology of knee joint tissues was examined, and the degeneration of joint cartilage was assessed. Mouse knee chondrocytes were isolated and induced with IL-1β, followed by ART treatment. ART alleviates OA in mice by elevating ubiquitin carboxyl-terminal hydrolase 7 (USP7) expression, and USP7 inhibitor (P22077) treatment mitigated the protective effects of ART on chondrocytes. We also showed that USP7 mediated the deubiquitination of forkhead box protein O1 (FoxO1), while FoxO1 alleviated chondrocyte injury. In addition, FoxO1 promoted metastasis-associated protein MTA1 (MTA1) transcription, and downregulation of MTA1 exacerbated chondrocyte injury. Our study identifies that USP7/FoxO1/MTA1 is a key signaling cascade in the treatment of ART on OA. [Display omitted] • ART treatment increases USP7 expression in the bone tissues of mice with DMM. • Reduced USP7 expression exacerbates cartilage tissue damage in osteoarthritic mice. • USP7 mediates deubiquitination modification of FoxO1. • FoxO1 alleviates chondrocyte damage in OA by promoting the transcription of MTA1. • Increased MTA1 expression ameliorates chondrocyte damage in OA. [ABSTRACT FROM AUTHOR]

Wei Wang,1,2,* Zaoxiu Hu,3,* Mingsheng Ma,4 Haoyuan Yin,4 Yunchao Huang,1 Guangqiang Zhao,1 Xin Cui,1 Qinling Sun,1 Yantao Yang,1 Yichen Yang,1 Biying Wang,1 Lianhua Ye1 1Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 2Department of Thoracic Surgery, Taihe Hospital (Hubei University of Medicine), Shiyan, People’s Republic of China; 3Department of Pathology, The Third Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 4Department of Thoracic Surgery, The Sixth Affiliated Hospital of Kunming Medical University, Yuxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lianhua YeDepartment of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University, No. 519 Kunzhou Road, Xishan District, Kunming City, Yunnan Province, People’s Republic of ChinaEmail lhye1204@aliyun.comPurpose: Currently, there is no uniform standard to guide postoperative adjuvant chemotherapy for patients with multifocal non-small cell lung cancers (NSCLCs) ≤ 3 cm. Therefore, there is an urgent need to explore prognostic molecular markers to identify high-risk patients with multifocal NSCLCs ≤ 3 cm. We aimed to explore the potential value of metastasis-associated protein 1(MTA1) expression in risk stratification of patients with multifocal NSCLCs ≤ 3 cm.Methods: We retrospectively analyzed the clinical data and postoperative survival data of patients with multifocal NSCLCs ≤ 3 cm. Paraffin-embedded tissue sections were used for immunohistochemistry. Semiquantitative immunoreactivity scoring (IRS) system was used to evaluate the nuclear expression of MTA1. SPSS software (version 23.0) was used to analyze the data.Results: The IRS of MTA1 nuclear expression in 259 lesions of 119 patients ranged from 2.2 to 11.7 (median: 5.6). Our results showed that MTA1 expression was highest in high-risk pathological subtypes of lung adenocarcinoma. MTA1 expression in multiple primary lung cancers (MPLCs) was lower than that in intrapulmonary metastases (IPMs). The median follow-up duration was 25.97 months. The disease-free survival (DFS) of patients with MPLCs was significantly better than that of patients with IPMs, and the DFS of patients with high MTA1 expression was significantly worse than that of patients with low MTA1 expression. Multivariate Cox analysis showed that high MTA1 expression (hazard ratio: 7.937, 95% confidence interval: 2.433– 25.64, p =0.001) was a statistically significant predictor of worse DFS in patients with multifocal NSCLCs ≤ 3 cm.Conclusion: MTA1 expression can stratify the risk in patients with multifocal NSCLCs ≤ 3 cm. Patients with MTA1 immunohistochemical score > 5.6 are at a high risk of postoperative recurrence, and these patients may benefit from postoperative adjuvant chemotherapy.Keywords: multifocal, non-small cell lung cancer, MTA1, multiple primary lung cancers, intrapulmonary metastases, risk of postoperative recurrence

Objective To determine the effect of tumor metastasis-associated gene 1 (MTA1) on the sensitivity of HeLa cells to radiotherapy, and to clarify its molecular mechanism. Methods The transcriptome differences between MTA1 knocked down Hela cells and control cells were analyzed, and the differentially expressed genes (DEGs) was used to perform Gene-Set Enrichment Analysis (GSEA) and Gene Ontology (GO) cluster analysis. Flow cytometry was used to detect apoptosis in MTA1-overexpressed HeLa cells and control cells before and after 10 Gy X-ray irradiation. Cloning formation assay and real-time cellular analysis (RTCA) were used to monitor the cell proliferation before and after 2 Gy X-ray irradiation. To dissect the underlying molecular mechanisms of MTA1 affecting the sensitivity of radiotherapy, the proteins encoded by the DEGs were selected to construct a protein-protein interaction network, the expression of γ-H2AX was detected by immunofluorescence assay, and the expression levels of γ-H2AX, ß-CHK2, PARP and cleaved caspase 3 were measured by western blot. Results By transcriptome sequencing analysis, we obtained 649 DEGs, of which 402 genes were up-regulated in MTA1 knockdown HeLa cells and 247 genes were down-regulated. GSEA results showed that DEGs associated with MTA1 were significantly enriched in cellular responses to DNA damage repair processes. The results of flow cytometry showed that the apoptosis rate of MTA1 over-expression group (15.67±0.81)% after 10 Gy X-ray irradiation was significantly lower than that of the control group [(40.27± 2.73)%, P < 0.001]. After 2 Gy X-ray irradiation, the proliferation capacity of HeLa cells overexpressing MTA1 was higher than that of control cells (P = 0.024). The numbers of colon in MTA1 over-expression group before and after 2 Gy X-ray irradiation were (176±7) and (137±7) respectively, higher than (134±4) and (75±4) in control HeLa cells (P<0.05). The results of immunofluorescence assay showed that there was no significant expression of γ-H2AX in MTA1 overexpressed and control HeLa cells without X-ray irradiation. Western blot results showed that the expression level of ß-CHK2 in MTA1-overexpressing HeLa cells (1.04±0.06) was higher than that in control HeLa cells (0.58± 0.25, P = 0.036) after 10 Gy X-ray irradiation. The expression levels of γ-H2AX, PARP, and cleaved caspase 3 were 0.52±0.13, 0.52±0.22, and 0.63±0.18, respectively, in HeLa cells overexpressing MTA1, which were lower than 0.87±0.06, 0.78±0.12 and 0.90±0.12 in control cells (P> 0.05). Conclusions This study showed that MTA1 is significantly associated with radiosensitivity in cervical cancer HeLa cells. MTA1 over-expression obviously reduces the sensitivity of cervical cancer cells to X-ray irradiation. Mechanism studies initially indicate that MTA1 reduces the radiosensitivity of cervical cancer cells by inhibiting cleaved caspase 3 to suppress apoptosis and increasing ß-CHK2 to promote DNA repair. [ABSTRACT FROM AUTHOR]

Distant metastasis is the main cause of death in non-small cell lung cancer (NSCLC) patients. The mechanism of metastasis-associated protein 1(MTA1) in NSCLC has not been fully elucidated. This study aimed to reveal the mechanism of MTA1 in the invasion and metastasis of NSCLC.Bioinformatics analysis and our previous results showed that MTA1 was highly expressed in NSCLC tissues and correlated with tumor progression. Knockout of MTA1 by CRISPR/Cas9 significantly inhibited the migration and invasion of H1299 cells, but enhanced cell adhesion. Stable overexpression of MTA1 by lentivirus transfection had opposite effects on migration, invasion and adhesion of A549 cells. The results of in vivo experiments in nude mouse lung metastases model confirmed the promotion of MTA1 on invasion and migration. Tight junction protein 1 (TJP1) was identified by immunoprecipitation and mass spectrometry as an interacting protein of MTA1 involved in cell adhesion. MTA1 inhibited the expression level of TJP1 protein and weakened the tight junctions between cells. More importantly, the rescue assays confirmed that the regulation of MTA1 on cell adhesion, migration and invasion was partially attenuated by TJP1.In Conclusion, MTA1 inhibits the expression level of TJP1 protein co-localized in the cytoplasm and membrane of NSCLC cells, weakens the tight junctions between cells, and changes the adhesion, migration and invasion capabilities of cells, which may be the mechanism of MTA1 promoting the invasion and metastasis of NSCLC. Thus, targeting the MTA1-TJP1 axis may be a promising strategy for inhibiting NSCLC metastasis.

Accumulated experimental data have suggested that natural plant products may be effective miRNA-modulating chemopreventive and therapeutic agents. Dietary polyphenols such as flavonoids, stilbenes, and lignans, among others, have been intensively studied for their miRNA-mediated cardioprotective, antioxidant, anti-inflammatory and anticancer properties. The aim of this review is to outline known stilbene-regulated miRNAs in cancer, with a special focus on the interplay between various miRNAs and MTA1 signaling in prostate cancer. MTA1 is an epigenetic reader and an oncogenic transcription factor that is overexpressed in advanced prostate cancer and metastasis. Not surprisingly, miRNAs that are linked to MTA1 affect cancer progression and the metastatic potential of cells. Studies led to the identification of MTA1-associated pro-oncogenic miRNAs, which are regulated by stilbenes such as resveratrol and pterostilbene. Specifically, it has been shown that inhibition of the activity of the MTA1 regulated oncogenic miR-17 family of miRNAs, miR-22, and miR-34a by stilbenes leads to inhibition of prostatic hyperplasia and tumor progression in mice and reduction of proliferation, survival and invasion of prostate cancer cells in vitro. Taken together, these findings implicate the use of resveratrol and its analogs as an attractive miRNA-mediated chemopreventive and therapeutic strategy in prostate cancer and the use of circulating miRNAs as potential predictive biomarkers for clinical development. [ABSTRACT FROM AUTHOR]

Background: Mitochondrial dysfunction plays a crucial role in Parkinson’s disease (PD) pathogenesis. The present study was undertaken to investigate the effects of Telmisartan (TEL), an angiotensin II type 1 receptor (AT1R) blocker, on the mitochondria-specific genes expression in a mouse model of Parkinsonism. Materials and methods: Mice were divided into 5 groups with 6 in each; Group I received 0.5% CMC (control) + saline, Group II received 0.5% CMC + 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (positive control), Group III & IV received MPTP + TEL 3 and 10 mg/kg, p.o. respectively, Group V received TEL 10 mg/kg, p.o. (drug control). MPTP was given 80 mg/kg intraperitoneal in two divided doses (40 mg/kg × 2 at 16 h time interval). Vehicle or TEL was administered 1 h before the MPTP injection. Motor function was assessed 48 h after the first dose of MPTP and animals were euthanized to collect brain. Results: Mice intoxicated with MPTP showed locomotor deficits and significant upregulation of α-synuclein (α-syn), downregulation of metastasis-associated protein 1 (MTA1), and Ubiquitin C-terminal hydrolase L1 (UCHL1) in the substantia nigra pars compacta (SNpc) and Striatum (STr) regions of brains. In addition, MPTP intoxication down-regulated mitochondria-specific genes such as DJ-1, PTEN-induced putative kinase 1 (PINK1), Parkin, enriched with leucine repeats kinase 2 (LRRK2) gene expfression. Pre-treatment with TEL restored locomotor functions and upregulated PINK1, Parkin, LRRK2, DJ-1, MTA1 and UCHL1. Conclusion: The present study evidences that TEL has the ability to improve mitochondrial functions in PD.

Accumulated experimental data have suggested that natural plant products may be effective miRNA-modulating chemopreventive and therapeutic agents. Dietary polyphenols such as flavonoids, stilbenes, and lignans, among others, have been intensively studied for their miRNA-mediated cardioprotective, antioxidant, anti-inflammatory and anticancer properties. The aim of this review is to outline known stilbene-regulated miRNAs in cancer, with a special focus on the interplay between various miRNAs and MTA1 signaling in prostate cancer. MTA1 is an epigenetic reader and an oncogenic transcription factor that is overexpressed in advanced prostate cancer and metastasis. Not surprisingly, miRNAs that are linked to MTA1 affect cancer progression and the metastatic potential of cells. Studies led to the identification of MTA1-associated pro-oncogenic miRNAs, which are regulated by stilbenes such as resveratrol and pterostilbene. Specifically, it has been shown that inhibition of the activity of the MTA1 regulated oncogenic miR-17 family of miRNAs, miR-22, and miR-34a by stilbenes leads to inhibition of prostatic hyperplasia and tumor progression in mice and reduction of proliferation, survival and invasion of prostate cancer cells in vitro. Taken together, these findings implicate the use of resveratrol and its analogs as an attractive miRNA-mediated chemopreventive and therapeutic strategy in prostate cancer and the use of circulating miRNAs as potential predictive biomarkers for clinical development.

Metastasis-associated protein 1 (MTA1) is an emerging transcriptional co-regulator and was found to be aberrantly expressed in different types of cancers. MTA1 has been reported to regulate multiple cancer-related signalling pathways leading to tumour progression and metastasis. Recently, MTA1 was also implicated in cancer metabolism, where it was found to regulate the 'Warburg effect' to drive breast cancer cell invasion. Overall, the functional dynamism of MTA1 can be attributed to its dual co-regulatory effects in regulating a diverse array of target genes involved in cell proliferation, DNA damage repair, angiogenesis, invasion, migration, metastasis, and metabolism in different types of cancers. In this review, we have attempted to provide a brief summary of MTA1 as a modulator of the hallmarks of cancer. [ABSTRACT FROM AUTHOR]

Background: Metastatic breast cancer to the lungs is a serious, life-threatening complication that is difficult to cure. Circulating tumor cells play a key role in the metastatic spread of breast cancer to the lungs via the lymphatic or circulatory system. Palmatine is a protoberberine alkaloid, identified as an active component of traditional African herbal preparations. Palmatine has antimetastatic and antiproliferative effects. The inhibitory activity of palmatine on the metastatic colonization of triple negative breast cancer cells in the lungs was investigated in this study. Methods: 4T1 triple breast cancer cells were transplanted synergically to the thoracic duct of the female balb/c mice via the lymphatic system. Palmatine 1, 5 and 10 mg/kg were administered for 28 days. The lungs were analyzed for levels of arterial blood gas, histological damage, immunohistochemical expression of the metastasis-associated protein 1 (MTA1) and tumor suppressor p53 (p53). Results: Administering palmatine 1–10 mg/kg dose dependently improved hypoxemia, ameliorated metastasis associated lung injury; histology score of 3.33 ± 0.33, 1.67 ± 0.33, 1.33 ± 0.33, decreased lung MTA1 (2.19 ± 0.12, 1.83 ± 0.04, 1.84 ± 0.05) and increased p53 expression (1.99 ± 0.06, 2.27 ± 0.12, 2.34 ± 0.12) respectively. Conclusion: Palmatine preserved lung morphology and demonstrated therapeutic potential in aiding the treatment of lung metastasis. [ABSTRACT FROM AUTHOR]

Introduction Breast cancer (BC) is a common malignant tumor affecting women across the world. LncRNAs are frequently implicated in the course of BC. The current study set out to determine the specific effect of lncRNA AGAP2-AS1 on BC cell resistance to apoptosis. Methods AGAP2-AS1 expression patterns in BC tissues and cells were evaluated. si-AGAP2-AS1 was transfected into MCF-7 cells, followed by the assessment of cell proliferation and apoptosis. In addition to detection of MTA1 expression patterns, the binding relation between AGAP2-AS1 and HuR was verified using RNA pull-down and RNA immunoprecipitation. Next, the regulation enrichment of AGAP2-AS1- and HuR to H3K27ac recruitment in the MTA1 promoter was analyzed. MCF-7 cell resistance to apoptosis was observed after the combined experiment of histone deacetylase inhibitor M344 and si-AGAP2-AS1. Lastly, xenografts tumors were established to detect tumor weight and volume, tumor apoptosis and growth as well as expression of AGAP2-AS1 and MTA1. Results AGAP2-AS1 was overexpressed in BC tissues and cells, and AGAP2-AS1 silencing inhibited cell proliferation but facilitated apoptosis. Physiologically, AGAP2-AS1 bound to HuR to stabilize its own expression, and AGAP2-AS1-HuR complex upregulated H3K27ac levels in the MTA1 promoter region to elevate MTA1 promoter activity and MTA1 expression. H3K27ac upregulation partially-annulled the promotive effect of si-AGAP2-AS1 on BC apoptosis by upregulating MTA1. si-AGAP2-AS1 in vivo inhibited MTA1 expression to enhance apoptosis and suppress tumor growth. Conclusion Collectively, our findings indicated that AGAP2-AS1 bound to HuR to stabilize its own expression, and AGAP2-AS1-HuR complex enhanced H3K27ac levels in the MTA1 promoter region to improve MTA1 promoter activity and MTA1 expression in BC cells, so as to augment BC cell resistance to apoptosis. [ABSTRACT FROM AUTHOR]

Background: The MTA1 protein encoded by metastasis-associated protein 1 (MTA1) is a key component of the ATP-dependent nucleosome remodeling and deacetylase (NuRD) complex, which is widely upregulated in cancers. MTA1 extensively affects downstream gene expression by participating in chromatin remodeling. Although it was defined as a metastasis-associated gene in first reports and metastasis is a process prominently affected by the tumor microenvironment, whether it affects the microenvironment has not been investigated. In our study, we elucidated the regulatory effect of MTA1 on tumor-associated macrophages (TAMs) and how this regulation affects the antitumor effect of cytotoxic T lymphocytes (CTLs) in the tumor microenvironment of colorectal cancer. Methods: We detected the cytokines affected by MTA1 expression via a cytokine antibody array in control HCT116 cells and HCT116 cells overexpressing MTA1. Multiplex IHC staining was conducted on a colorectal cancer tissue array from our cancer cohort. Flow cytometry (FCM) was performed to explore the polarization of macrophages in the coculture system and the antitumor killing effect of CTLs in the coculture system. Bioinformatics analysis was conducted to analyze the Cancer Genome Atlas (TCGA) colorectal cancer cohort and single-cell RNA-seq data to assess the immune infiltration status of the TCGA colorectal cancer cohort and the functions of myeloid cells. Results: MTA1 upregulation in colorectal cancer was found to drive an immunosuppressive tumor microenvironment. In the tumor microenvironment of MTA1-upregulated colorectal cancer, although CD8+ T cells were significantly enriched, macrophages were significantly decreased, which impaired the CTL effect of the CD8+ T cells on tumor cells. Moreover, upregulated MTA1 in tumor cells significantly induced infiltrated macrophages into tumor-associated macrophage phenotypes and further weakened the cytotoxic effect of CD8+ T cells. Conclusion: Upregulation of MTA1 in colorectal cancer drives an immunosuppressive tumor microenvironment by decreasing the microphages from the tumor and inducing the residual macrophages into tumor-associated microphage phenotypes to block the activation of the killing CTL, which contributes to cancer progression. [ABSTRACT FROM AUTHOR]

Endometriosis is a benign disease that shares some malignant features. Epithelial-mesenchymal transition (EMT) is involved in the pathogenesis of endometriosis. Metastasis-associated protein 1 (MTA1) plays an important role in various cancers by promoting EMT, yet there are no studies on its function in endometriosis. In the present study, we found that MTA1 was highly expressed in the ectopic endometrium of endometriosis patients and that the expression of MTA1 was related to the revised American Fertility Society stage. MTA1 facilitated endometrial stroma cell proliferation, migration, and invasion by inducing EMT, and the promotion function and MTA1 expression were suppressed by resveratrol, a natural polyphenol. Moreover, we revealed that MTA1 induced EMT through interaction with ZEB2. The findings in a mouse endometriosis model further showed that MTA1 and ZEB2 were upregulated in ectopic tissues and that resveratrol inhibited the growth of ectopic lesions and expression of MTA1 and ZEB2. Taken together, we demonstrate that MTA1 is a protein that promotes EMT via interacting with ZEB2 in the pathogenesis of endometriosis, and may be a target of resveratrol.

Metastasis Associated 1 (MTA1) chromatin modifier oncoprotein played a crucial role in both normal and genotoxic stress situations for genome maintenance. To investigates MTA1 regulatory pattern with drug resistance abilities in breast primary carcinoma to advanced invasive stages for identification of cancer adapting defense system. We design rationale in silico pipeline from data retrieval to analysis i.e. gene enrichment analysis performed by GeneCards Version 5.1: THE HUMAN GENE DATABASE (www.genecards.org), UALCAN database (www.ualcan.path.uab.edu) for analyzing MTA1 gene expression and promoter methylation in both breasts normal and cancerous tissue samples, cBioPortal for Cancer Genomics (www.cbioportal.org) database for MTA1 mutation analysis and finally analyzed MTA1 functional association with anticancer drugs in breast malignancy via online CCLE GDSC toolkit (www.public.tableau.com/CCLE_GDSC_Correlations). Our results revealed MTA1 overexpression aggressive behavior in stage II, stage III, TNBC-LAR, TNBC-M, TNBC-UNS, IDC, ILC, and post-menopause events of breast malignancy. MTA1 upregulation strongly promotes primary tumor transformation into invasive metastatic carcinoma by hijacking the host lymphatic system and cytokine signaling in both ductal and glandular breast cancers. MTA1 upregulation in the African-American population invites to design de novo model of cancer cell homeostasis under a reduced supply of vegetable nutrients, local-foreign stress, and replicative capacity for metastasis. MTA1 showed a hypomethylation profile that reflects regulatory strength under stress-mediated situations for higher events of transcription. In drug resistance analysis MTA1 has strong resistance towards 15 anti-cancer drugs that confirmed its previously reported behavior of genotoxic stress adaptation for metastasis. Our in silico evidence invites us to design a comprehensive strategy against MTA1 mediated stress managing proteome. In the future there is an urgent need to explore MTA1 shared stress coped protein networks for early diagnosis and better prognosis.

Background: Metastatic breast cancer to the lungs is a serious, life-threatening complication that is difficult to cure. Circulating tumor cells play a key role in the metastatic spread of breast cancer to the lungs via the lymphatic or circulatory system. Palmatine is a protoberberine alkaloid, identified as an active component of traditional African herbal preparations. Palmatine has antimetastatic and antiproliferative effects. The inhibitory activity of palmatine on the metastatic colonization of triple negative breast cancer cells in the lungs was investigated in this study.Methods: 4T1 triple breast cancer cells were transplanted synergically to the thoracic duct of the female balb/c mice via the lymphatic system. Palmatine 1, 5 and 10 mg/kg were administered for 28 days. The lungs were analyzed for levels of arterial blood gas, histological damage, immunohistochemical expression of the metastasis-associated protein 1 (MTA1) and tumor suppressor p53 (p53).Results: Administering palmatine 1–10 mg/kg dose dependently improved hypoxemia, ameliorated metastasis associated lung injury; histology score of 3.33 ± 0.33, 1.67 ± 0.33, 1.33 ± 0.33, decreased lung MTA1 (2.19 ± 0.12, 1.83 ± 0.04, 1.84 ± 0.05) and increased p53 expression (1.99 ± 0.06, 2.27 ± 0.12, 2.34 ± 0.12) respectively.Conclusion: Palmatine preserved lung morphology and demonstrated therapeutic potential in aiding the treatment of lung metastasis.

BackgroundThe MTA1 protein encoded by metastasis-associated protein 1 (MTA1) is a key component of the ATP-dependent nucleosome remodeling and deacetylase (NuRD) complex, which is widely upregulated in cancers. MTA1 extensively affects downstream gene expression by participating in chromatin remodeling. Although it was defined as a metastasis-associated gene in first reports and metastasis is a process prominently affected by the tumor microenvironment, whether it affects the microenvironment has not been investigated. In our study, we elucidated the regulatory effect of MTA1 on tumor-associated macrophages (TAMs) and how this regulation affects the antitumor effect of cytotoxic T lymphocytes (CTLs) in the tumor microenvironment of colorectal cancer.MethodsWe detected the cytokines affected by MTA1 expression via a cytokine antibody array in control HCT116 cells and HCT116 cells overexpressing MTA1. Multiplex IHC staining was conducted on a colorectal cancer tissue array from our cancer cohort. Flow cytometry (FCM) was performed to explore the polarization of macrophages in the coculture system and the antitumor killing effect of CTLs in the coculture system. Bioinformatics analysis was conducted to analyze the Cancer Genome Atlas (TCGA) colorectal cancer cohort and single-cell RNA-seq data to assess the immune infiltration status of the TCGA colorectal cancer cohort and the functions of myeloid cells.ResultsMTA1 upregulation in colorectal cancer was found to drive an immunosuppressive tumor microenvironment. In the tumor microenvironment of MTA1-upregulated colorectal cancer, although CD8+ T cells were significantly enriched, macrophages were significantly decreased, which impaired the CTL effect of the CD8+ T cells on tumor cells. Moreover, upregulated MTA1 in tumor cells significantly induced infiltrated macrophages into tumor-associated macrophage phenotypes and further weakened the cytotoxic effect of CD8+ T cells.ConclusionUpregulation of MTA1 in colorectal cancer drives an immunosuppressive tumor microenvironment by decreasing the microphages from the tumor and inducing the residual macrophages into tumor-associated microphage phenotypes to block the activation of the killing CTL, which contributes to cancer progression.

Abstract Background The metastasis-associated gene 1 (MTA1) has been extensively reported as a crucial oncogene, and its abnormal expression has been associated with the progression of numerous cancers. However, the role of MTA1 in renal cell carcinoma (RCC) progression and metastasis remains unclear. Herein, we investigated the expression of MTA1 and its role in RCC. Methods 109 matched clear cell RCCs (ccRCCs) and corresponding normal tissue samples were analyzed via immunohistochemistry to test the expression of MTA1. Human A498 cell lines were transfected with pcDNA3.1-Flag (control) or Flag-MTA1 to overexpress MTA1 or with specific interfering RNA (si-MTA1) or specific interfering negative control to knockdown MTA1 expression. Transfected cells were used in wound healing and transwell invasion assay. Quantitative real time polymerase chain reaction was used to assess the effect of MTA1 on MMP2/MMP9 and E-cadherin gene expression. Western blot was used to qualify the phosphorylation of p65. Results Herein, we found a significantly increased expression of MTA1 in 109 ccRCCs, compared to the corresponding normal tissue. In addition, the overexpression of MTA1 in A498 cells facilitated cell migration and invasion, while the down-regulation of MTA1 expression using specific interfering RNA sequences could decrease cell migration and invasion. Furthermore, we showed that MTA1 is up-regulated in ccRCCs, which contributes to the migration and invasion of human kidney cancer cells by mediating the expression of MMP2 and MMP9 through the NF-κB signaling pathway. Similarly, we found that MTA1 could regulate E-cadherin expression in RCCs. Conclusions MTA1 is overexpressed in RCC and is involved in the progression of RCC through NF-κB.

Abstract Objective This study is aimed to explore the role of miR-543 in non-small cell lung cancer (NSCLC), and verify whether miR-543 targets metastasis associated protein 1 (MTA1) to affect tumorigenesis and angiogenesis in NSCLC. Methods Firstly, miR-543 mimic and inhibitor were transfected into A549 cells and H1299 cells. The cells proliferation was tested by MTT and clone formation. The cells apoptosis was analyzed by cytometry. Tube formation assay was used to measure the vascularization of cells. qRT-PCR and Western Blot were used to measure the MTA1 expression. Dual-luciferase assay was used to analyze whether miR-543 targets MTA1. Secondly, MTA1 mimic and inhibitor were transfected into cells to analyze the effect of MTA1 on proliferation and angiogenesis in NSCLC cells. Lastly, the nude mice were used to verify the effect of miR-543 on tumorigenesis and angiogeneisis in NSCLC via modulating MATA1. Results miR-543 overexpression could apparently promote cells proliferation and angiogeneisis in NSCLC cells. Meanwhile, the MTA1 expression was increased after transfecting miR-543 mimic. Dual luciferase reporter assay revealed MTA1 was a downstream target of miR-543. Further studies showed that inhibition of MTA1 weakened the role of miR-543 overexpression in NSCLC cells. Vivo experiments revealed that miR-543 promoted cells proliferation and angiogenesis in tumor tissues via modulating MTA1. Conclusion miR-543 could target MTA1 to promote tumorigenesis and angiogenesis in NSCLC via targeting MTA1.

Ning Zhou, Xiaofei Zhu, Libo Man Department of Urology, Beijing Jishuitan Hospital, Beijing 100035, People’s Republic of ChinaCorrespondence: Libo Man Email libo_man@sina.comPurpose: Long non-coding RNAs have been found to be involved in bladder cancer development. This article studied LINC00963 effects on bladder cancer progression to provide a novel treatment target.Patients and Methods: Totally 56 bladder cancer patients participated in this research. Bladder cancer cells were transfected. Cell counting kit 8 assay and clone formation experiment were used for cell viability and colony formation detection. Cell migration and invasion were determined by Transwell experiment. LINC00963 distribution was explored by cytoplasmic and nuclear extract isolation and quantitative real-time polymerase chain reaction. Luciferase reporter experiment and RNA pulldown experiment were performed to detect the relationship between these two genes. The cancer genome atlas analysis was used for the detection of metastasis-associated protein 1 (MTA1) expression in bladder cancer.Results: LINC00963 was seriously up-regulated in bladder cancer patients. High LINC00963 expression indicated high histological grade and low survival. LINC00963 was obviously up-regulated in bladder cancer cells. Knockdown of LINC00963 significantly reduced bladder cancer cells viability, colony formation, migration and invasion. Luciferase reporter experiment and RNA pulldown experiment revealed that LINC00963 promoted MTA1 expression via directly inhibiting miR-766-3p. MTA1 was up-regulated in bladder cancer patients. MTA1 up-regulation reversed the inhibitory effect of LINC00963 knockdown on bladder cancer cell viability, migration and invasion.Conclusion: LINC00963 functions as an oncogene in bladder cancer by regulating the miR-766-3p/MTA1 axis.Keywords: bladder cancer, LINC00963, miR-766-3p, MTA1, progression

BackgroundFOXP3, as a tumour suppressor gene, has a vital function in inhibiting the metastasis of breast cancer cells, but the mechanisms by which it inhibits metastasis have not been fully elucidated. This study intended to explore a new mechanism by which FOXP3 inhibits breast cancer metastasis.MethodsBioinformatic analysis was performed to identify potential downstream molecules of FOXP3. The function of FOXP3 in inhibiting MTA1 expression at the mRNA and protein levels was verified by real-time PCR and Western blot analysis. The interaction between FOXP3 and the MTA1 promoter was verified by transcriptomic experiments. In vitro and in vivo experiments were used to determine whether the regulation of MTA1 by FOXP3 affected the invasion and migration of breast cancer cells. Immunohistochemistry was adopted to explore the correlation between the expression levels of FOXP3 and MTA1 in breast cancer samples.ResultsBioinformatics-based sequencing suggested that MTA1 is a potential downstream molecule of FOXP3. FOXP3 downregulated the expression of MTA1 in breast cancer cells by directly inhibiting MTA1 promoter activity. Importantly, FOXP3’s regulation of MTA1 affected the ability of breast cancer cells to invade and metastasize in vitro and in vivo. Moreover, analysis of clinical specimens showed a significant negative correlation between the expression levels of FOXP3 and MTA1 in breast cancer.ConclusionWe systematically explored a new mechanism by which FOXP3 inhibits breast cancer metastasis via the FOXP3-MTA1 pathway.

OBJECTIVE: Long non-coding RNA (lncRNA), is essential for the development and progression of cancers. LncRNA regulates target gene expression by sponging the corresponding microRNA (miRNA) during tumorigenesis. This work aimed to explore the role of one lncRNA, ELFN1−AS1, in colorectal cancer (CRC) development and elucidate the pertinent signaling pathway. PATIENTS AND METHODS: First, we found that ELFN1−AS1 was highly abundant in the human CRC tissues and cell lines. Silence of ELFN1−AS1 expression reduced cell proliferation, colony formation, migration and invasion, while inducing apoptosis in vitro; moreover, knockdown of ELFN1−AS1 decreased the size and weight of tumor in vivo. RESULTS: Luciferase reporter assay revealed that ELFN1−AS1 interacted with miR-1205 and suppressed its expression. In addition, miR-1205 could bind to the 3ʹ untranslated region (3ʹ-UTR) of Metastasis Associated Protein1 (MTA1) and inhibited ELFN1−AS1 expression. More importantly, overexpression of MTA1 completely rescued the phenotype of ELFN1−AS1 knockdown. CONCLUSIONS: In sum, our study demonstrated that ELFN1−AS1 sponges miR-1205 to upregulate MTA1, which is essential for CRC cell proliferation, migration, and invasion as well as apoptosis induction. [ABSTRACT FROM AUTHOR]

Background: FOXP3, as a tumour suppressor gene, has a vital function in inhibiting the metastasis of breast cancer cells, but the mechanisms by which it inhibits metastasis have not been fully elucidated. This study intended to explore a new mechanism by which FOXP3 inhibits breast cancer metastasis. Methods: Bioinformatic analysis was performed to identify potential downstream molecules of FOXP3. The function of FOXP3 in inhibiting MTA1 expression at the mRNA and protein levels was verified by real-time PCR and Western blot analysis. The interaction between FOXP3 and the MTA1 promoter was verified by transcriptomic experiments. In vitro and in vivo experiments were used to determine whether the regulation of MTA1 by FOXP3 affected the invasion and migration of breast cancer cells. Immunohistochemistry was adopted to explore the correlation between the expression levels of FOXP3 and MTA1 in breast cancer samples. Results: Bioinformatics-based sequencing suggested that MTA1 is a potential downstream molecule of FOXP3. FOXP3 downregulated the expression of MTA1 in breast cancer cells by directly inhibiting MTA1 promoter activity. Importantly, FOXP3's regulation of MTA1 affected the ability of breast cancer cells to invade and metastasize in vitro and in vivo. Moreover, analysis of clinical specimens showed a significant negative correlation between the expression levels of FOXP3 and MTA1 in breast cancer. Conclusion: We systematically explored a new mechanism by which FOXP3 inhibits breast cancer metastasis via the FOXP3-MTA1 pathway. [ABSTRACT FROM AUTHOR]

Background/Aim: Metastasis-associated protein 1 (MTA1) plays a role in ATP-dependent nucleosome disruption activity and histone deacetylase activity and may indicate DNA methylation activity. MTA1 may also be involved in the progression of oral squamous cell carcinoma (OSCC). Patients and Methods: MTA1 immunoreactivity was analyzed using immunohistochemical (IHC) staining analysis in specimens from 281 OSCC patients. Kaplan-Meier analysis was used to determine the prognostic value of MTA1 for overall survival. Results: High MTA1 expression was significantly associated with female gender and lymph node metastasis. Multivariate analyses showed the independent prognostic role of high MTA1 expression in patients with OSCC of poorer mean survival. Conclusion: MTA1 expression, detected by IHC staining, could be an independent prognostic marker for patients of OSCC. [ABSTRACT FROM AUTHOR]

Adipose tissue-derived stem cells (ADSCs) are a kind of stem cells with multi-directional differentiation potential, which mainly restore tissue repair function and promote cell regeneration. It can be directionally differentiated into Schwann-like cells to promote the repair of peripheral nerve injury. Glial cell line-derived neurotrophic factor (GDNF) plays an important role in the repair of nerve injury, but the underlying mechanism remains unclear, which seriously limits its further application.The study aimed to identify the molecular mechanism by which overexpression of glial cell line–derived neurotrophic factor (GDNF) facilitates the differentiation of ADSCs into Schwann cells, enhancing nerve regeneration after injury. In vitro, ADSCs overexpressing GDNF for 48 h exhibited changes in their morphology, with 80% of the cells having two or more prominences. Compared with that of ADSCs, GDNF-ADSCs exhibited increased expression of the Schwann cell marker S100, nerve damage repair-related factors.ADSC cells in normal culture and ADSC cells were overexpressing GDNF(GDNF-ADSCs) were analysed using TMT-Based Proteomic Analysis and revealed a significantly higher expression of MTA1 in GDNF-ADSCs than in control ADSCs. Hes1 expression was significantly higher in GDNF-ADSCs than in ADSCs and decreased by MTA1 silencing, along with a simultaneous decrease in the expression of S100 and nerve damage repair factors. These findings indicate that GDNF promotes the differentiation of ADSCs into Schwann cells and induces factors that accelerate peripheral nerve damage repair. [Display omitted] • GDNF overexpression promotes the differentiation of ADSCs into Schwann cells and increases the expression of factors related to nerve injury repair. • GDNF regulates MTA1 during the differentiation of ADSCs into Schwann cells. • GDNF regulates Hes1 during the differentiation of ADSCs into Schwann cells. • Inhibition of MTA1 decreases the expression of Hes1 during the differentiation of ADSCs into Schwann cells. • Overexpression of GDNF in ADSCs enhances MTA1 expression, which transcriptionally regulates the downstream Hes1 molecule expression promoting differentiation of ADSCs to Schwann cells. [ABSTRACT FROM AUTHOR]

Abstract Background Exosomes are small membrane-bound vesicles that contribute to tumor progression and metastasis by mediating cell-to-cell communication and modifying the tumor microenvironment at both local and distant sites. However, little is known about the predominant factors in exosomes that contribute to breast cancer (BC) progression. MTA1 is a transcriptional co-regulator that can act as both a co-activator and co-repressor to regulate pathways that contribute to cancer development. MTA1 is also one of the most up-regulated proteins in cancer, whose expression correlates with cancer progression, poor prognosis and increased metastatic potential. Methods We identified MTA1 in BC exosomes by antibody array and confirmed expression of exosome-MTA1 across five breast cancer cells lines. Ectopic expression of tdTomato-tagged MTA1 and exosome transfer were examined by fluorescent microscopy. CRISPR/Cas9 genetic engineering was implemented to knockout MTA1 in MCF7 and MDA-MB-231 breast cancer cells. Reporter assays were used to monitor hypoxia and estrogen receptor signaling regulation by exosome-MTA1 transfer. Results Ectopic overexpression of tdTomato-MTA1 in BC cell lines demonstrated exosome transfer of MTA1 to BC and vascular endothelial cells. MTA1 knockout in BC cells reduced cell proliferation and attenuated the hypoxic response in these cells, presumably through its co-repressor function, which could be rescued by the addition of exosomes containing MTA1. On the other hand, consistent with its co-activator function, estrogen receptor signaling was enhanced in MTA1 knockout cells and could be reversed by addition of MTA1-exosomes. Importantly, MTA1 knockout sensitized hormone receptor negative cells to 4-hydroxy tamoxifen treatment, which could be reversed by the addition of MTA1-exosomes. Conclusions This is the first report showing that BC exosomes contain MTA1 and can transfer it to other cells resulting in changes to hypoxia and estrogen receptor signaling in the tumor microenvironment. These results, collectively, provide evidence suggesting that exosome-mediated transfer of MTA1 contributes to BC progression by modifying cellular responses to important signaling pathways and that exosome-MTA1 may be developed as a biomarker and therapeutic target for BC.

Abstract Background As the first member of the metastasis-associated protein (MTA) family, MTA1 and another MTA family member, MTA2, have both been reported to promote breast cancer progression and metastasis. However, the difference and relationship between MTA1 and MTA2 have not been fully elucidated. Methods Transwell assays were used to assess the roles of MTA1 and MTA2 in the metastasis of ZR-75-30 luminal B breast cancer cells in vitro. Immunoblotting and qRT-PCR were used to evaluate the effect of MTA1 overexpression on MTA2. Proteases that cleave MTA2 were predicted using an online web server. The role of neutrophil elastase (NE) in MTA1 overexpression-induced MTA2 downregulation was confirmed by specific inhibitor treatment, knockdown, overexpression and immunocytochemistry, and NE cleavage sites in MTA2 were confirmed by MTA2 truncation and mutation. The effect of MTA1 overexpression on the intrinsic inhibitor of NE, elafin, was detected by qRT-PCR, immunoblotting and treatment with inhibitors. Results MTA1 overexpression inhibited, while MTA2 promoted the metastasis of ZR-75-30 cells in vitro. MTA1 overexpression downregulated MTA2 expression at the protein level rather than the mRNA level. NE was predicted to cleave MTA2 and was responsible for MTA1 overexpression-induced MTA2 degradation. NE was found to cleave MTA2 in the C-terminus at the 486, 497, 542, 583 and 621 sites. MTA1 overexpression activated NE by downregulating elafin in a histone deacetylase- and DNA methyltransferase-dependent manner. Conclusions MTA1 and MTA2 play opposing roles in the metastasis of ZR-75-30 luminal B breast cancer cells in vitro. MTA1 downregulates MTA2 at the protein level by epigenetically repressing the expression of elafin and releasing the inhibition of neutrophil elastase, which cleaves MTA2 in the C-terminus at multiple specific sites.

Global incidence and mortality associated with hepatocellular carcinoma (HCC) is steadily increasing. Metastasis-associated 1 (MTA1) can induce tumorigenesis and metastatic progression in HCC. However, the mechanistic details of MTA1-mediated regulation of HCC has not been completely defined. Epigenetic histone modification is closely related to tumor development. Histone cluster 1 H1 family member c (H1.2) is important for epigenetic histone modification and chromatin remodeling; however, whether it has a role in HCC tumorigenesis is not known. In the current study, we confirmed that MTA1 promoted HCC cell growth and migration. Our results further show that MTA1 inhibited the phosphorylation of histone cluster 1 H1 family member c (H1.2) at threonine-146 residue (T146) (H1.2T146ph). MTA1 inhibited H1.2T146ph by mediating proteasomal degradation of the DNA protein kinase (DNA-PK). Pharmacological inhibition of proteasomal degradation of DNA-PK or genetic ablation of E3 ligase mouse double minute 2 (MDM2) rescued expression of DNA-PK, and subsequent phosphorylation of H1.2. MTA1's role in HCC was inhibited by ectopic expression of H1.2T146ph in HCC cell lines. Our results showed that H1.2T146ph can bind to MTA1 target genes. Collectively, our study confirms that MTA1 functions as an oncogene and promotes HCC progression. The epigenetic histone modifier H1.2T146ph exerts critical role in the regulation of MTA1-induced tumorigenesis. MTA1 regulates posttranslational activation of H1.2 by regulating the cognate kinase, DNA-PK, via the ubiquitin proteasome system. MTA1 expression was inversely correlated to both DNA-PK and phosphorylated H1.2 in HCC tissue specimens compared to tumor adjacent normal hepatic tissue, revealing that the MTA1/MDM2/DNA-PK/H1.2 is an important therapeutic axis in HCC.

Prostate cancer often metastasizes to the bone, leading to morbidity and mortality. While metastasis‐associated protein 1 (MTA1) is highly overexpressed in metastatic tumors and bone metastatic lesions, its exact role in the development of metastasis is unknown. Here, we report the role of MTA1 in prostate cancer progression and bone metastasis in vitro and in vivo. We found that MTA1 silencing diminished formation of bone metastases and impaired tumor growth in intracardiac and subcutaneous prostate cancer xenografts, respectively. This was attributed to reduced colony formation, invasion, and migration capabilities of MTA1 knockdown cells. Mechanistic studies revealed that MTA1 silencing led to a significant decrease in the expression of cathepsin B (CTSB), a cysteine protease critical for bone metastasis, with an expected increase in the levels of E‐cadherin in both cells and xenograft tumors. Moreover, meta‐analysis of clinical samples indicated a positive correlation between MTA1 and CTSB. Together, these results demonstrate the critical role of MTA1 as an upstream regulator of CTSB‐mediated events associated with cell invasiveness and raise the possibility that targeting MTA1/CTSB signaling in the tumor may prevent the development of bone metastasis in prostate cancer.

Abstract Background Tetrandrine is a bisbenzylisoquinoline alkaloid isolated from the Chinese medicinal herb Stephania tetrandra S. Moore. We previously demonstrated that tetrandrine exhibits potent antitumor effects in many types of cancer cells. In this study, we investigated the effects of tetrandrine on human hepatocellular carcinoma (HCC) metastasis. Methods The invasion and migration effects were evaluated via wound healing and transwell assays. Immunofluorescence and western blotting analyses were used to investigate the levels of epithelial-mesenchymal transition (EMT)-related protein. A metastasis model was established to investigate the inhibitory effect of tetrandrine on hepatocellular carcinoma metastasis in vivo. Results Tetrandrine inhibits HCC invasion and migration by preventing cell EMT. The underlying mechanism was closely associated with tetrandrine-induced human liver cell autophagy, which inhibits Wnt/β-catenin pathway activity and decreases metastatic tumor antigen 1 (MTA1) expression to modulate cancer cell metastasis. Conclusion Our findings demonstrate, for the first time, that tetrandrine plays a significant role in the inhibition of human hepatocellular carcinoma metastasis and provide novel insights into the application of tetrandrine in clinical HCC treatment.

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Objective: This study is aimed to explore the role of miR-543 in non-small cell lung cancer (NSCLC), and verify whether miR-543 targets metastasis associated protein 1 (MTA1) to affect tumorigenesis and angiogenesis in NSCLC. Methods: Firstly, miR-543 mimic and inhibitor were transfected into A549 cells and H1299 cells. The cells proliferation was tested by MTT and clone formation. The cells apoptosis was analyzed by cytometry. Tube formation assay was used to measure the vascularization of cells. qRT-PCR and Western Blot were used to measure the MTA1 expression. Dual-luciferase assay was used to analyze whether miR-543 targets MTA1. Secondly, MTA1 mimic and inhibitor were transfected into cells to analyze the effect of MTA1 on proliferation and angiogenesis in NSCLC cells. Lastly, the nude mice were used to verify the effect of miR-543 on tumorigenesis and angiogeneisis in NSCLC via modulating MATA1. Results: miR-543 overexpression could apparently promote cells proliferation and angiogeneisis in NSCLC cells. Meanwhile, the MTA1 expression was increased after transfecting miR-543 mimic. Dual luciferase reporter assay revealed MTA1 was a downstream target of miR-543. Further studies showed that inhibition of MTA1 weakened the role of miR-543 overexpression in NSCLC cells. Vivo experiments revealed that miR-543 promoted cells proliferation and angiogenesis in tumor tissues via modulating MTA1. Conclusion: miR-543 could target MTA1 to promote tumorigenesis and angiogenesis in NSCLC via targeting MTA1. [ABSTRACT FROM AUTHOR]

Metastasis-associated protein-1 (MTA1) has been recently identified as a unique gene which plays a key role in tumorigenesis and progression of cancer cells. The object behind this study is to evaluate MTA1 immunoexpression and its relationship with predictive value of point-based grading systems in salivary mucoepidermoid carcinoma. A total of 22 formalin-fixed, paraffin-embedded specimens of mucoepidermoid carcinoma were prepared for immunohistochemical staining with MTA1 antibodies. Assessment of MTA1 immunostaining was achieved by counting the proportion of positively-stained tumor cells in 5 high power fields; and staining was analyzed in relation to tumor grading systems and other clinicopathologic features. MTA1 showed nuclear and cytoplasmic expression in varying intensity in 95% of cases. Non-significant correlation was found between MTA1expression and age, gender, site of the tumor (p > 0.05). However, statistically significant correlation was observed between MTA1expression and clinical stage, as well, to nodal involvement (p = 0.009 and 0.007; respectively). Regarding histologic grade, high MTA1 level was significantly associated with grade of tumors categorized by Auclair and Brandwein systems (p = 0.001 and 0.009; respectively). MTA1 expression significantly correlates with tumor grade and progression, and it has a potential role to predict the prognosis of salivary MEC. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is an important cause of cancer death worldwide, and hepatitis B virus (HBV) infection is a major etiology, particularly in the Asia-Pacific region. Lack of sensitive biomarkers for early diagnosis of HCC and lack of effective therapeutics for patients with advanced HCC are the main reasons for high HCC mortality; these clinical needs are linked to the molecular heterogeneity of hepatocarcinogenesis. Animal models are the basis of preclinical and translational research in HBV-related HCC (HBV-HCC). Recent advances in methodology have allowed the development of several animal models to address various aspects of chronic liver disease, including HCC, which HBV causes in humans. Currently, multiple HBV-HCC animal models, including conventional, hydrodynamics-transfection-based, viral vector-mediated transgenic, and xenograft mice models, as well as the hepadnavirus-infected tree shrew and woodchuck models, are available. This review provides an overview of molecular mechanisms and animal models of HBV-HCC. Additionally, the metastatic tumor antigen 1 (MTA1), a cancer-promoting molecule, was introduced as an example to address the importance of a suitable animal model for studying HBV-related hepatocarcinogenesis.

Background and objective It has been proven that metastasis associated protein 1 (MTA1) was correlated with tumor invasion and migration and poor prognosis of several malignant carcinomas. The prognostic role of MTA1 expression in lung cancer remained controversial, we performed this meta-analysis to assess the prognostic value of MTA1 expression in lung cancer. Methods A systematic literature search was conducted to identify eligible studies which dealing with the relationship between MTA1 expression and prognosis of lung cancer in PubMed, Embase, Wanfang databases, China Biology Medicine disc and China National Knowledge Infrastructure. The pooled hazard ratio (HR) were used to assess the relationship between MTA1 expression and prognosis of lung cancer. All data were analysed using the Stata 12.0 software. Results A total of 712 Chinese lung cancer patients from 8 studies were included in this meta-analysis. There was significant heterogeneity existed in these studies (I2=59.0%, P=0.017), so we used a random effects model to calculate the pooled HR=2.07 (95%CI: 1.42-3.02, P

Interleukin-17 (IL-17) has been shown to promote development of prostate, colon, skin, lung, breast, and pancreatic cancer. The purpose of this study was to determine if IL-17 regulates MTA1 expression and its biological consequences. Human cervical cancer HeLa and human prostate cancer DU-145 cell lines were used to test if IL-17 regulates metastasis associated 1 (MTA1) mRNA and protein expression using quantitative reverse transcription-polymerase chain reaction and Western blot analysis, respectively. Cell migration and invasion were studied using wound healing assays and invasion chamber assays. Thirty-four human cervical tissues were stained for IL-17 and MTA1 using immunohistochemical staining. We found that IL-17 increased MTA1 mRNA and protein expression in both cell lines. Cell migration was accelerated by IL-17, which was abolished by knockdown of MTA1 expression with small interference RNA (siRNA). Further, cell invasion was enhanced by IL-17, which was eliminated by MTA1 knockdown. Human cervical intra-epithelial neoplasia (CIN) and cervical cancer tissues had increased number of IL-17-positive cells and MTA1 expression compared to normal cervical tissues. The number of IL-17-positive cells was positively correlated with MTA1 expression. These findings demonstrate that IL-17 upregulates MTA1 mRNA and protein expression to promote HeLa and DU-145 cell migration and invasion.

In eukaryotes, N 6 -methyladenosine (m 6 A) RNA modification plays a crucial role in governing the fate of RNA molecules and has been linked to various developmental processes. However, the phyletic distribution and functions of genetic factors responsible for m 6 A modification remain largely unexplored in fungi. To get insights into the evolution of m 6 A machineries, we reconstructed global phylogenies of potential m 6 A writers, readers, and erasers in fungi. Substantial copy number variations were observed, ranging from up to five m 6 A writers in early-diverging fungi to a single copy in the subphylum Pezizomycotina, which primarily comprises filamentous fungi. To characterize m 6 A factors in a phytopathogenic fungus Fusarium graminearum , we generated knockout mutants lacking potential m 6 A factors including the sole m 6 A writer MTA1 . However, the resulting knockouts did not exhibit any noticeable phenotypic changes during vegetative and sexual growth stages. As obtaining a homozygous knockout lacking MTA1 was likely hindered by its essential role, we generated MTA1 -overexpressing strains ( MTA1 -OE). The MTA1 -OE5 strain showed delayed conidial germination and reduced hyphal branching, suggesting its involvement during vegetative growth. Consistent with these findings, the expression levels of MTA1 and a potential m 6 A reader YTH1 were dramatically induced in germinating conidia, followed by the expression of potential m 6 A erasers at later vegetative stages. Several genes including transcription factors, transporters, and various enzymes were found to be significantly upregulated and downregulated in the MTA1 -OE5 strain. Overall, our study highlights the functional importance of the m 6 A methylation during conidial germination in F. graminearum and provides a foundation for future investigations into m 6 A modification sites in filamentous fungi.IMPORTANCE N 6 -methyladenosine (m 6 A) RNA methylation is a reversible posttranscriptional modification that regulates RNA function and plays a crucial role in diverse developmental processes. This study addresses the knowledge gap regarding phyletic distribution and functions of m 6 A factors in fungi. The identification of copy number variations among fungal groups enriches our knowledge regarding the evolution of m 6 A machinery in fungi. Functional characterization of m 6 A factors in a phytopathogenic filamentous fungus Fusarium graminearum provides insights into the essential role of the m 6 A writer MTA1 in conidial germination and hyphal branching. The observed effects of overexpressing MTA1 on fungal growth and gene expression patterns of m 6 A factors throughout the life cycle of F. graminearum further underscore the importance of m 6 A modification in conidial germination. Overall, this study significantly advances our understanding of m 6 A modification in fungi, paving the way for future research into its roles in filamentous growth and potential applications in disease control., Competing Interests: The authors declare no conflict of interest.

Scope: Resistance of castrate-resistant prostate cancer (CRPC) to enzalutamide (Enz) involves the expression of constitutively active androgen receptor splice variant (AR-V7). In addition to altered AR pathways, CRPC is characterized by "non-AR-driven" signaling, which includes an overexpression of metastasis-associated protein 1 (MTA1). Combining natural compounds with anticancer drugs may enhance drug effectiveness while reducing adverse effects. In this study, the in vitro and in vivo anticancer effects of Gnetin C (GnC) alone and in combination with Enz against CRPC are examined., Methods and Results: The effects of GnC alone and in combination with Enz are assessed by cell viability, clonogenic survival, cell migration, and AR and MTA1 expression using 22Rv1 cells. The tumor growth in vivo is assessed by bioluminescent imaging, western blots, RT-PCR, and IHC. GnC alone and in combined treatment inhibit cell viability, clonogenic survival and migration, and AR and MTA1 expression in 22Rv1 cells. The underlying AR- and MTA1-targeted anticancer mechanisms of treatments in vivo involve inhibition of proliferation and angiogenesis, and induction of apoptosis., Conclusion: The findings demonstrate that GnC alone and GnC combined with Enz effectively inhibits AR- and MTA1-promoted tumor-progression in advanced CRPC, which indicates its potential as a novel therapeutic approach for CRPC., (© 2023 Wiley-VCH GmbH.)

Metastasis Associated Protein1 (MTA1) is a chromatin modifier and its expression is significantly associated with prognosis of many cancers. However, its role in glucose metabolism remains unexplored. Here, we report that MTA1 has a significant role in glucose metabolism where MTA1 regulates the LDHA expression and activity and subsequently its function in breast cancer motility. The results showed that MTA1 expression is positively correlated with the LDHA expression levels in breast cancer patients. Further, it was found that MTA1 is necessary for the optimal expression of LDHA. The underlying molecular mechanism involves the interaction of MTA1 with c-Myc and recruitment of MTA1-c-Myc complex on to the LDHA promoter to regulate its transcription. Consequently, the LDHA knock down using LDHA specific siRNA in MCF7 cells stably expressing MTA1 reduced the migration of MCF7 cells. Altogether these findings revealed the regulatory role for MTA1 in LDHA expression and its resulting biological function. • MTA1 interacts with the genes of glucose metabolism. • MTA1 regulates LDHA expression and its activity. • MTA1 interacts with c-Myc. • LDHA mediates MTA1 mediated cell motility. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Recent researches have revealed the role of long noncoding RNAs (lncRNAs) in the development of tumors. In this study, lncRNA LUCAT1 was explored to identify how it affected the progression of cervical cancer. PATIENTS AND METHODS: Quantitative Real-time polymerase chain reaction (qRT-PCR) was used to detect LUCAT1 expression in both cervical cancer cells and tissue samples. Moreover, the associations between LUCAT1 expression level and patients' overall survival rate were explored, respectively. In addition, cell proliferation assay and transwell assay were conducted. Furthermore, the underlying mechanism was explored via performing qRT-PCR and Western blot assay. RESULTS: By comparing with the expression level in corresponding ones, the LUCAT1 expression level in cervical cancer samples was significantly higher. Moreover, expression level of LUCAT1 was negatively correlated with patients' overall survival time. In addition, after LUCAT1 was overexpressed, cell proliferation, cell invasion and migration capacities were promoted in vitro. In addition, the mRNA and protein expressions of MTA1 were upregulated after LUCAT1 was overexpressed. Furthermore, it was found that the expression level of MTA1 was positively related to LUCAT1 expression level in cervical cancer tissues. CONCLUSIONS: We showed that LUCAT1 could enhance proliferation, invasion and migration of cervical cancer cells through upregulating MTA1, which might offer a potential therapeutic choice for patients with cervical cancer. [ABSTRACT FROM AUTHOR]

Though metastasis-associated protein 1 (MTA1) is widely overexpressed in human cancers and is associated with advanced clinicopathological characteristics and survival in related diseases, the association between MTA1 and endometrial cancer (EC) is little known and needs to be studied. Western blot and immunohistochemistry were used to analyze protein expression level of cells and tissues, while real-time PCR was used for RNA detection. Bioinformatics tool analysis revealed the relationship between MTA1 and clinicopathological characteristics and survival. CCK-8 assay, colony-formation assay, cell scratch assay, and Transwell assay were performed to determine cell proliferation, migration and invasion abilities, respectively. The expression level of MTA1 was significantly higher in human EC tissues than in normal endometrium. MTA1 expression was correlated positively with lymph nodes metastasis and poor survival rate in EC. Experimentally overexpressed MTA1 could promote cell proliferation, migration and invasion abilities of EC cell lines Ishikawa, HEC-1B, and RL-952, while reduction of MTA1 inhibited these cell biological behaviors. Moreover, MTA1 could also reverse the negative effect of miR-30c, a direct modulator of MTA1, on EC cells. Our research also revealed that overexpression of MTA1 contributed to EC tumor growth, while knockdown of MTA1 resulted in tumor growth inhibition. Additionally, the phosphorylation levels of mTOR (S2448) and 4E-BP1 (T37/46) changed significantly along with AKT (T308) under regulation of MTA1, both in vivo and vitro. Our results showed that MTA1, as a downstream target of miR-30c, might promote EC progression via AKT/mTOR/4E-BP1 pathway, which indicated the potential therapy target of MTA1 in EC. • An overexpression of MTA1 was associated with poor prognosis in EC. • MTA1 facilitates EC development both in vitro and vivo. • MTA1 reverses the effect of its moderator, miR-30c, on EC cells. • The AKT/mTOR/4E-BP1 pathway may be the key pathway regulated by MTA1 in EC. • Silencing of MTA1 results in inhibition of EC. [ABSTRACT FROM AUTHOR]