TGF-β–Induced Upregulation of <i>malat1</i> Promotes Bladder Cancer Metastasis by Associating with suz12

Fan, Yu; Shen, Bing; Tan, Mingyue; Mu, Xinyu; Yan, Qin; Zhang, Fang; Liu, Yong

doi:10.1158/1078-0432.ccr-13-1455

Cited by 380 publications

(353 citation statements)

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“…LncRNA MALAT1 was first recognized as a marker for metastasis development in the early stages of lung adenocarcinoma14 and recently in PCa 40. It has been shown to play an important role in multiple cancers via various mechanisms, such as acting as miRNA sponges, enhancing EMT and stimulating apoptosis or autophagy 12, 17, 18, 19, 20. Recently, MALAT1 has been confirmed to induce chemoresistance to oxaliplatin of colorectal cancer by promoting EZH2 41 and regulate multidrug resistance of hepatocellular carcinoma cells by sponging miR‐216b to modulate the expression of HIF‐2 α that is related to autophagy pathway 42.…”

Section: Discussionmentioning

confidence: 99%

Retracted: Long noncoding RNA MALAT1 enhances the docetaxel resistance of prostate cancer cells via miR‐145‐5p‐mediated regulation of AKAP12

Dong¹,

Lü²,

Xu³

et al. 2018

J Cellular Molecular Medi

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Our present work was aimed to study on the regulatory role of MALAT1/miR‐145‐5p/AKAP12 axis on docetaxel (DTX) sensitivity of prostate cancer (PCa) cells. The microarray data (GSE33455) to identify differentially expressed lncRNAs and mRNAs in DTX‐resistant PCa cell lines (DU‐145‐DTX and PC‐3‐DTX) was retrieved from the Gene Expression Omnibus (GEO) database. QRT‐PCR analysis was performed to measure MALAT1 expression in DTX‐sensitive and DTX‐resistant tissues/cells. The human DTX‐resistant cell lines DU145‐PTX and PC3‐DTX were established as in vitro cell models, and the expression of MALAT1, miR‐145‐5p and AKAP12 was manipulated in DTX‐sensitive and DTX‐resistant cells. Cell viability was examined using MTT assay and colony formation methods. Cell apoptosis was assessed by TUNEL staining. Cell migration and invasion was determined by scratch test (wound healing) and Transwell assay, respectively. Dual‐luciferase assay was applied to analyse the target relationship between lncRNA MALAT1 and miR‐145‐5p, as well as between miR‐145‐5p and AKAP12. Tumour xenograft study was undertaken to confirm the correlation of MALAT1/miR‐145‐5p/AKAP12 axis and DTX sensitivity of PCa cells in vivo. In this study, we firstly notified that the MALAT1 expression levels were up‐regulated in clinical DTX‐resistant PCa samples. Overexpressed MALAT1 promoted cell proliferation, migration and invasion but decreased cell apoptosis rate of PCa cells in spite of DTX treatment. We identified miR‐145‐5p as a target of MALAT1. MiR‐145‐5p overexpression in PC3‐DTX led to inhibited cell proliferation, migration and invasion as well as reduced chemoresistance to DTX, which was attenuated by MALAT1. Moreover, we determined that AKAP12 was a target of miR‐145‐5p, which significantly induced chemoresistance of PCa cells to DTX. Besides, it was proved that MALAT1 promoted tumour cell proliferation and enhanced DTX‐chemoresistance in vivo. There was an lncRNA MALAT1/miR‐145‐5p/AKAP12 axis involved in DTX resistance of PCa cells and provided a new thought for PCa therapy.

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Section: Discussionmentioning

confidence: 99%

Retracted: Long noncoding RNA MALAT1 enhances the docetaxel resistance of prostate cancer cells via miR‐145‐5p‐mediated regulation of AKAP12

Dong¹,

Lü²,

Xu³

et al. 2018

J Cellular Molecular Medi

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“…Similarly, the lncRNA Malat1, which is upregulated by transforming growth factor-TGF in bladder cancer cells, induces EMT 168 . TP63 (which encodes p63) is expressed in the basal and intermediate cell layers of the normal urothelium.…”

Section: Emt and Metastasismentioning

confidence: 99%

Molecular biology of bladder cancer: new insights into pathogenesis and clinical diversity

2014

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Correspondence to M.A.K. m.a.knowles@leeds.ac.uk 2 Preface Urothelial carcinoma of the bladder comprises two long-recognised disease entities with distinct molecular features and clinical outcome. Low-grade, non-muscle-invasive tumours recur frequently but rarely progress to muscle invasion, whereas muscle invasive tumours are usually diagnosed de novo and frequently metastasize. Recent genome-wide expression and sequencing studies identify genes and pathways that are key drivers of urothelial cancer and reveal a more complex picture with multiple molecular subclasses that cut across conventional grade and stage groupings. This improved understanding of molecular features, disease pathogenesis and heterogeneity provides new opportunities for prognostic application, disease monitoring and personalised therapy.Bladder cancer is the most common cancer of the urinary tract with approximately 380,000 new cases and 150,000 deaths per year worldwide 1 . It ranks fifth among cancers in men in Western countries.Epidemiological studies identify a range of environmental risk factors, many of which reflect exposure to excreted carcinogenic molecules (BOX 1). Recent genome-wide association studies have also identified germline variants that contribute to risk 2 .In Europe and North America, more than 90% of bladder cancers are urothelial carcinoma. These tumours are staged using the Tumour Nodes Metastasis (TNM) system 3 , which describes the extent of invasion (Tis-T4), and graded according to their cellular characteristics. Two classification systems are in current use 4, 5 .At diagnosis the majority of bladder cancers (~ 60%) are non-muscle-invasive (NMIBC) (stage Ta) NMIBCs frequently recur (50-70%) but infrequently progress to invasion (10-15%) 6 and five-year survival is ~90%. These patients are monitored by cystoscopy and may have multiple resections over many years.Improved monitoring is needed, ideally via urine analysis, which could reduce the morbidity and costs associated with cystoscopy. Although risk tables provide a prognostic tool 7 , no molecular biomarkers accurately predict disease progression. For these patients, localised therapies to remove residual neoplastic and preneoplastic cells post-resection may have major impacts on both quality of life and in health economic terms. MIBCs (>stage T2) have less favourable prognosis with five-year survival <50% and common progression to metastasis (BOX1). Treatment has not advanced for several decades and new approaches to systemic therapy are needed 8 .Improved treatment requires detailed understanding of urothelial carcinoma pathogenesis and molecular biology. A model has evolved, taking into account both histopathological and molecular features. This socalled 'two-pathway' model proposes that papillary NMIBC develops via epithelial hyperplasia and recruitment of a branching vasculature. MIBCs are proposed to develop via flat dysplasia and carcinoma in situ (CIS). The molecular characteristics of MIBC and NMIBC are highly distinct (Tables 1 and 2). Whilst 3 m...

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“…Malat1 associates with Suz12, another component of PRC2, and regulates EMT genes, and knockdown of either Malat1 or Suz12 inhibits tumor metastasis. 131 Thus, the EMT program involves chromatin remodeling, generating a plastic epigenetic landscape characterized by bivalent genes, i.e., genes with both active H3K4me3 and repressive H3K27me3 marks. 101 Such "poised" chromatin is then available to undergo the inverse changes during the MET process that is important for somatic reprogramming to induced pluripotent stem cells.…”

mentioning

confidence: 99%

Reprogramming during epithelial to mesenchymal transition under the control of TGFβ

Tan¹,

Olsson

Moustakas

2014

Cell Adhesion & Migration

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Epithelial-mesenchymal transition (EMT) refers to plastic changes in epithelial tissue architecture. Breast cancer stromal cells provide secreted molecules, such as transforming growth factor b (TGFb), that promote EMT on tumor cells to facilitate breast cancer cell invasion, stemness and metastasis. TGFb signaling is considered to be abnormal in the context of cancer development; however, TGFb acting on breast cancer EMT resembles physiological signaling during embryonic development, when EMT generates or patterns new tissues. Interestingly, while EMT promotes metastatic fate, successful metastatic colonization seems to require the inverse process of mesenchymal-epithelial transition (MET). EMT and MET are interconnected in a timedependent and tissue context-dependent manner and are coordinated by TGFb, other extracellular proteins, intracellular signaling cascades, non-coding RNAs and chromatin-based molecular alterations. Research on breast cancer EMT/MET aims at delivering biomolecules that can be used diagnostically in cancer pathology and possibly provide ideas for how to improve breast cancer therapy.

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TGF-β–Induced Upregulation of malat1 Promotes Bladder Cancer Metastasis by Associating with suz12

Cited by 380 publications

References 28 publications

Retracted: Long noncoding RNA MALAT1 enhances the docetaxel resistance of prostate cancer cells via miR‐145‐5p‐mediated regulation of AKAP12

Retracted: Long noncoding RNA MALAT1 enhances the docetaxel resistance of prostate cancer cells via miR‐145‐5p‐mediated regulation of AKAP12

Molecular biology of bladder cancer: new insights into pathogenesis and clinical diversity

Reprogramming during epithelial to mesenchymal transition under the control of TGFβ

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