Long noncoding RNA NEAT1 drives aggressive endometrial cancer progression via miR-361-regulated networks involving STAT3 and tumor microenvironment-related genes

Journal of Experimental & Clinical Cancer Research, Год журнала: 2019, Номер 38(1)

Опубликована: Июль 8, 2019

High-grade endometrioid and serous endometrial cancers (ECs) are an aggressive subtype of ECs without effective therapies. The reciprocal communication between tumor cells their surrounding microenvironment drives progression. Long noncoding RNAs (lncRNAs) key mediators tumorigenesis metastasis. However, little is known about the role lncRNAs in EC progression remodeling. We performed array-based lncRNA analysis a parental HEC-50 cell population derivatives with highly invasive, sphere-forming, paclitaxel (TX)-resistant characteristics. characterized roles NEAT1 mediating vitro vivo explored molecular events downstream NEAT1. identified 10 upregulated expression (NEAT1, H19, PVT1, UCA1, MIR7-3HG, SNHG16, HULC, RMST, BCAR4 LINC00152) downregulated (MEG3, GAS5, DIO3OS, MIR155HG, LINC00261, FENDRR, MIAT, TMEM161B-AS1, HAND2-AS1 NBR2) sphere-forming TX-resistant derivatives. was markedly early-stage tissue samples, high predicted poor prognosis. Inhibiting small hairpin (shRNAs) diminished cellular proliferation, invasion, sphere formation, xenograft growth improved TX response cells. showed that functions as oncogenic sponge for suppressor microRNA-361 (miR-361), which suppresses formation resistance by directly targeting oncogene STAT3. Furthermore, miR-361 also suppressed multiple prometastatic genes microenvironment-related genes, including MEF2D, ROCK1, WNT7A, VEGF-A, PDE4B, KPNA4. initiates miR-361-mediated network to drive These data support rationale inhibiting signaling potential therapeutic strategy overcoming chemoresistance.

Язык: Английский

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The Effects of Cannabidiol and Prognostic Role of TRPV2 in Human Endometrial Cancer

International Journal of Molecular Sciences, Год журнала: 2020, Номер 21(15), С. 5409 - 5409

Опубликована: Июль 29, 2020

Several studies support, both in vitro and vivo, the anti-cancer effects of cannabidiol (CBD), a transient receptor potential vanilloid 2 (TRPV2) ligand. TRPV2, often dysregulated tumors, is associated with altered cell proliferation aggressiveness. Endometrial cancer (EC) historically divided type I endometrioid EC II non-endometrioid EC, poor prognosis. Treatment options chemotherapy combinations radiation showed only limited efficacy. Since no data are reported concerning TRPV2 expression as well CBD aim this study was to evaluate biopsies lines models. Overall survival (OS), progression-free (PFS), viability, migration, chemo-resistance have been evaluated. Results show that increased malignancy tissue correlated shorter PFS (p = 0.0224). Moreover, over-expression Ishikawa line migratory ability response cisplatin. reduced activating predominantly apoptosis cells autophagy mixed cells. The improved chemotherapeutic drugs cytotoxic effects, enhanced by over-expression. Hence, could be considered marker for optimizing therapy might useful therapeutic option adjuvant therapy.

Язык: Английский

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LncRNA–miRNA–mRNA regulatory axes in endometrial cancer: a comprehensive overview

Archives of Gynecology and Obstetrics, Год журнала: 2022, Номер 306(5), С. 1431 - 1447

Опубликована: Фев. 18, 2022

Язык: Английский

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Pathology of Endometrial Carcinoma

Advances in experimental medicine and biology, Год журнала: 2016, Номер unknown, С. 75 - 96

Опубликована: Дек. 1, 2016

Язык: Английский

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Molecular Basis of Tumor Heterogeneity in Endometrial Carcinosarcoma

Cancers, Год журнала: 2019, Номер 11(7), С. 964 - 964

Опубликована: Июль 9, 2019

Endometrial carcinosarcoma (ECS) represents one of the most extreme examples tumor heterogeneity among human cancers. ECS is a clinically aggressive, high-grade, metaplastic carcinoma. At morphological level, intratumor in due to an admixture epithelial (carcinoma) and mesenchymal (sarcoma) components that can include heterologous tissues, such as skeletal muscle, cartilage, or bone. Most ECSs belong copy-number high serous-like molecular subtype endometrial carcinoma, characterized by TP53 mutation frequently accompanied large number gene alterations, including amplification important oncogenes, CCNE1 c-MYC. However, proportion cases (20%) probably represent progression tumors initially belonging low endometrioid-like (characterized mutations genes PTEN, PI3KCA, ARID1A), after acquisition mutations. Only few microsatellite-unstable hypermutated type POLE-mutated, ultramutated type. A common characteristic all modulation involved process. Thus, phenotype associated with switch from E- N-cadherin, up-regulation transcriptional repressors E-cadherin, Snail Family Transcriptional Repressor 1 2 (SNAI1 SNAI2), Zinc Finger E-Box Binding Homeobox (ZEB1 ZEB2), down-regulation, others, members miR-200 family maintenance phenotype. Subsequent differentiation different types tissues increases modulates clinical behavior therapy response.

Язык: Английский

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PP2A: A Promising Biomarker and Therapeutic Target in Endometrial Cancer

Frontiers in Oncology, Год журнала: 2019, Номер 9

Опубликована: Июнь 4, 2019

Over the last decade, use of targeted therapies has immensely increased in treatment cancer. However, for endometrial carcinomas (ECs) lagged behind, although potential molecular markers have been identified. This is particularly problematic type II ECs, since these aggressive tumors are usually not responsive towards current standard therapies. Therefore, ECs responsible most EC-related deaths, indicating need new options. Interestingly, analyses uncovered frequent genetic alterations (up to 40%) PPP2R1A, encoding Aα subunit tumor suppressive heterotrimeric protein phosphatase 2A (PP2A). PPP2R1A mutations were also reported I and other common gynecologic cancers, albeit at much lower frequencies (0-7%). Nevertheless, PP2A inactivation latter cancer types via mechanisms, particular by expression Cancerous Inhibitor (CIP2A) Methyl Esterase-1 (PME-1) proteins. In this review, we discuss therapeutic direct indirect targeting compounds, possibly combination with anti-cancer drugs, EC. Furthermore, investigate status as a predictive and/or prognostic marker ECs.

Язык: Английский

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The Highly Recurrent PP2A Aα-Subunit Mutation P179R Alters Protein Structure and Impairs PP2A Enzyme Function to Promote Endometrial Tumorigenesis

Cancer Research, Год журнала: 2019, Номер 79(16), С. 4242 - 4257

Опубликована: Май 30, 2019

Somatic mutation of the protein phosphatase 2A (PP2A) Aα-subunit gene PPP2R1A is highly prevalent in high-grade endometrial carcinoma. The structural, molecular, and biological basis by which most recurrent carcinoma-specific site P179 facilitates features carcinoma malignancy has yet to be fully determined. Here, we used a series biochemical, approaches investigate impact P179R missense on PP2A function. Enhanced sampling molecular dynamics simulations showed that arginine-to-proline substitution at residue changes protein's stable conformation profile. A crystal structure tumor-derived mutant revealed marked A-subunit conformation. Binding catalytic subunit was significantly impaired, disrupting holoenzyme formation enzymatic activity. Cancer cells were dependent disruption for sustained tumorigenic potential, restoration wild-type Aα patient-derived P179R-mutant cell line restored enzyme function attenuated tumorigenesis metastasis vivo. Furthermore, small molecule-mediated therapeutic reactivation inhibited tumorigenicity These outcomes implicate functional inactivation as critical component disease pathogenesis. Moreover, they highlight potential strategy patients who harbor mutations. SIGNIFICANCE: This study characterizes recurrent, disease-specific driver target novel development.See related commentary Haines Huang, p. 4009.

Язык: Английский

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Recent Multiomics Approaches in Endometrial Cancer

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(3), С. 1237 - 1237

Опубликована: Янв. 22, 2022

Endometrial cancer is the most common gynecological cancers in developed countries. Many of mechanisms involved its initiation and progression remain unclear. Analysis providing comprehensive data on genome, transcriptome, proteome, epigenome could help selecting molecular markers targets endometrial cancer. Multiomics approaches can reveal disturbances multiple biological systems, giving a broader picture problem. However, they provide large amount that require processing further integration prior to analysis. There are several repositories multiomics datasets, including data, as well portals allowing analysis visualization, Oncomine, UALCAN, LinkedOmics, miRDB. have also been applied research order identify novel therapeutic targets. This review describes detail latest findings

Язык: Английский

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Landscape of Endometrial Cancer: Molecular Mechanisms, Biomarkers, and Target Therapy

Cancers, Год журнала: 2024, Номер 16(11), С. 2027 - 2027

Опубликована: Май 27, 2024

Endometrial cancer is one the most prevalent gynecological cancers and, unfortunately, has a poor prognosis due to low response rates traditional treatments. However, progress in molecular biology and understanding genetic mechanisms involved tumor processes offers valuable information that led current classification describes four subtypes of endometrial cancer. This review focuses on pathogenesis cancers, such as mutations, defects DNA mismatch repair pathway, epigenetic changes, or dysregulation angiogenic hormonal signaling pathways. The preclinical genomic investigations presented allowed for identification some molecules could be used biomarkers diagnose, predict, monitor progression Besides therapies known clinical practice, targeted therapy described new treatment involves identifying specific targets cells. By selectively inhibiting these targets, key pathways can disrupted while normal cells are protected. connection between vital fight against Ongoing research trials exploring use standard agents combination with other strategies like immunotherapy anti-angiogenesis improve outcomes personalize patients approach potential transform management patients. In conclusion, enhancing tools essential stratifying risk guiding surgery, adjuvant therapy, women addition, from this may have an value personalized patient’s life.

Язык: Английский

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Chimeric Antigen Receptor T Cell Immunotherapy for Gynecological Malignancies

Critical Reviews in Oncology/Hematology, Год журнала: 2025, Номер unknown, С. 104680 - 104680

Опубликована: Фев. 1, 2025

Язык: Английский

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