MTA1 promotes the invasion and migration of non-small cell lung cancer cells by downregulating miR-125b

Li, Yiyi; Chao, Yilan; Fang, Yuan; Wang, Jian; Wang, Min; Zhang, Hong; Ying, Min; Zhu, Xiaoxia; Wang, Haofei

doi:10.1186/1756-9966-32-33

Cited by 50 publications

(128 citation statements)

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“…They indicated that MTA1 upregulation was closely related to the invasion and metastasis of NSCLC. Following that, several studies were performed to investigate the role and mechanism of MTA1 in lung cancer promotion (24)(25)(26)(27)(28). However, only NSCLC tissues or cell lines were examined in these studies.…”

Section: Discussionmentioning

confidence: 99%

MTA1 downregulation inhibits malignant potential in a small cell lung cancer cell line

et al. 2014

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Abstract. As a component of the nuclear remodeling and deacetylation complex (NuRD complex), metastasis-associated gene 1 (MTA1) has been reported to play a key role in cancer malignancy. However, whether MTA1 functions in small cell lung cancer (SCLC) malignant behavior and whether it is feasible to be used as a therapeutic target have not been evaluated. The present study aimed to investigate the effects of MTA1 downregulation on SCLC malignancy. First we demonstrated the overexpression of MTA1 in SCLC specimens. After knocking down the MTA1 level by specific siRNA sequence, the biological consequences on proliferation, migration, invasion and apoptosis were evaluated. The results showed that MTA1 silencing had potent suppressive effects on SCLC proliferation, migration and invasion. Apoptosis but not cell cycle arrest was induced in the MTA1-silenced SCLC cells. In summary, MTA1 plays a critical role in regulating the malignant behaviors of SCLC. Depleting MTA1 level may be an effective strategy by which to suppress SCLC growth and metastasis in future biotherapeutic attempts. IntroductionLung cancer is one of the most deadly diseases and ranks first as the cause for cancer-related mortality (1). Small cell lung cancer (SCLC), accounting for ~15% of all lung cancer cases, is a highly aggressive subtype with neuroendocrine properties (2). Currently, for SCLC, there is no effective treatment strategy either through surgery or chemotherapy (3), attributed to its early dissemination and fast development of drug resistance after initiation of chemotherapy (4). The 5-year survival of SCLC patients is as low as 15% or less even after aggressive treatment (5). In light of targeted therapeutic approaches which have shown advantages over traditional strategies, new therapeutic targets must be explored based on the ongoing understanding of molecular mechanisms in lung cancer development and progression.Cancer development and progression are characterized by deregulated gene expression networks which drive the proliferation and metastasis of cancer cells (6). Among the deregulated cancer-related genes, metastasis-associated gene 1 (MTA1) is one of the key players involved in certain steps of cancer development (7). MTA1 is a component of the nuclear remodeling and deacetylation complex (NuRD complex) that affects gene expression ubiquitously (8). MTA1 has been reported to be overexpressed in a series of malignant diseases, including breast cancer (9), esophageal squamous cell carcinoma (10), oral squamous cell carcinoma (11), colon cancer (12) and nonsmall cell lung cancer (NSCLC) (13). Moreover, it has been shown to exert cancer progression in a number of cancer types, such as melanoma, esophageal squamous cell carcinoma and colon cancer, showing promise as a molecular target in cancer therapy strategy development (14). However, whether MTA1 also plays a key role in SCLC malignant behavior or whether it also bears promise in SCLC treatment needs to be ascertained before further potential MTA1-targeted therapeutics can b...

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Section: Discussionmentioning

confidence: 99%

MTA1 downregulation inhibits malignant potential in a small cell lung cancer cell line

et al. 2014

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“…Several cell biological studies have applied an siRNA approach for specific knock-down of MTA1 expression and succeeded in reducing cancer cell transformation, proliferation, clonal growth, VEGF expression, invasiveness, and migration [40,84,[86][87][88][89]. Furthermore, at least two microRNAs have been identified that interfere with MTA1 mRNA stabilization and could be used for MTA1 targeting [90,91].…”

Section: Further Perspectives In Targeting Mta1 and Concluding Remarksmentioning

confidence: 98%

Function and regulation of MTA1 and MTA3 in malignancies of the female reproductive system

Brüning

Blankenstein

Jückstöck

et al. 2014

Cancer Metastasis Rev

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The family of metastasis-associated (MTA) genes is a small group of transcriptional co-regulators which are involved in various physiological functions, ranging from lymphopoietic cell differentiation to the development and maintenance of epithelial cell adhesions. By recruiting histone-modifying enzymes to specific promoter sequences, MTA proteins can function both as transcriptional repressors and activators of a number of cancer-relevant proteins, including Snail, E-cadherin, signal transducer and activator of transcriptions (STATs), and the estrogen receptor. Their involvement in the epithelial-mesenchymal transition process and regulatory interactions with estrogen receptor activity has made MTA proteins highly interesting research candidates, especially in the field of hormone-sensitive breast cancer and malignancies of the female reproductive tract. This review focuses on the current knowledge about the function and regulation of MTA1 and MTA3 proteins in gynecological cancer, including ovarian, endometrial, and cervical tumors.

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“…This suggests that PCA not only induces apoptosis of tumor cells but also prevents them from metastasis, subsequently in this paper we report the possible mechanisms involved. Metastasis-associated gene 1 (MTA1), an integral part of the nucleosome remodeling and histone deacetylation (NuRD) complex, can inhibit the transcription of target genes by recruiting histone deacetylases into the promoter regions of target genes thus inducing histone deacetylation (Li et al, 2013). MTA1 is up-regulated in human tumors (Hofer et al, 2006) and increases the metastatic and invasive potential of carcinoma cells (Hofer et al, 2004;Kumar et al, 2003;Toh et al, 2004;Zhang et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of invasion and metastasis of human liver cancer HCCLM3 cells by portulacerebroside A

Qian¹,

Zheng²,

Chen³

et al. 2014

Pharmaceutical Biology

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Objective: This study investigates the effects of PCA in human liver cancer HCCLM3 cells on metastasis and invasion. Materials and methods: After the cells were treated with PCA (2.5, 5, and 10 mg/ml) for 6, 12, 24, or 48 h, adhesion, transwell invasion, and scratch tests were conducted and cell functions were evaluated. Western blot and FQ-RT-PCR assays explored the mechanism of PCA-inhibited invasion and metastasis in the cells. Results:The adhesion rate of the cells was suppressed at 0.5 h (79.4 ± 1.0, 68.7 ± 1.3, and 58.1 ± 1.3%, versus 100 ± 1.5% in the control), 1 h (78.2 ± 1.2, 70.9 ± 1.6, and 55.4 ± 1.9%, versus 100 ± 1.2% in the control), and 1.5 h (71.6 ± 1.1, 62.3 ± 0.9, and 50.4 ± 0.9%, versus 100 ± 1.1% in the control). The 24 h invasion ability was decreased (356.6 ± 11.2, 204.0 ± 17.6, and 113.0 ± 9.5%, versus 443.6 ± 15.4% in the control). The migration capability was also restrained by PCA for 24 h (324.8 ± 25.4, 250.4 ± 21.0, and 126.3 ± 10.1, versus 381.6 ± 30.6 in the control) and 48 h (470.3 ± 34.3, 404.0 ± 19.7, and 201.0 ± 15.4, versus 752.0 ± 63.6 in the control). There was an increase in the mRNA and protein expression levels of TIMP-2 and nm23-H1, inhibition in the mRNA expression of MTA1, MMP-2, and MMP-9, and suppression in the protein expression of MTA1, RhoA, Rac1/Cdc42, MMP-2, but not RhoC and MMP-9. Conclusion: PCA suppresses the invasion and metastasis of HCCLM3 cells possibly by modulation of the mRNA and protein expression of related parameters. This is the first study to reveal a new potential therapeutic application of PCA in antimetastatic therapy for liver cancer.

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MTA1 promotes the invasion and migration of non-small cell lung cancer cells by downregulating miR-125b

Cited by 50 publications

References 23 publications

MTA1 downregulation inhibits malignant potential in a small cell lung cancer cell line

MTA1 downregulation inhibits malignant potential in a small cell lung cancer cell line

Function and regulation of MTA1 and MTA3 in malignancies of the female reproductive system

Inhibition of invasion and metastasis of human liver cancer HCCLM3 cells by portulacerebroside A

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