Molecular Classification of Breast Cancer Utilizing Long Non-Coding RNA (lncRNA) Transcriptomes Identifies Novel Diagnostic lncRNA Panel for Triple-Negative Breast Cancer

Cancers, Journal Year: 2021, Volume and Issue: 13(21), P. 5350 - 5350

Published: Oct. 26, 2021

Breast cancer remains the world's most prevalent cancer, responsible for around 685,000 deaths globally despite international research efforts and advances in clinical management. While estrogen receptor positive (ER+), progesterone (PR+), human epidermal growth factor (HER2+) subtypes are easily classified can be targeted, there no direct diagnostic test triple-negative breast (TNBC), except lack of receptors expression. The identification long non-coding RNAs (lncRNAs) roles they play progression has recently proven to beneficial. In current study, we utilize RNA sequencing data identify lncRNA-based biomarkers associated with TNBC, ER+ subtypes, normal tissue. Marker Finder algorithm identified lncRNA transcript panel each molecular subtype receiver operating characteristic (ROC) analysis was used validate potential (area under curve (AUC) ≥8.0 p value < 0.0001). Focusing on findings from discovery cohort were validated an additional two cohorts, identifying 13 common transcripts enriched TNBC. Binary regression a four signature (ENST00000425820.1, ENST00000448208.5, ENST00000521666.1, ENST00000650510.1) highest power ENST00000671612.1 correlated worse refractory free survival (RFS). Our provides step towards finding novel TNBC therapeutic implications.

Language: Английский

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DIAPH3 promotes pancreatic cancer progression by activating selenoprotein TrxR1‐mediated antioxidant effects

Journal of Cellular and Molecular Medicine, Journal Year: 2020, Volume and Issue: 25(4), P. 2163 - 2175

Published: Dec. 20, 2020

Abstract Pancreatic cancer is a highly malignant tumour of the digestive tract which difficult to diagnose and treat. Approximately 90% cases arise from ductal adenocarcinoma glandular epithelium. The morbidity mortality disease have increased significantly in recent years. Its 5‐year survival rate <1% has one worst prognoses amongst tumours. low early‐stage diagnosis, high surgical cure rate. Selenium compounds produced by selenoamino acid metabolism may promote large amount oxidative stress subsequent unfolded reactions endoplasmic reticulum consuming NADPH cells, eventually lead apoptosis, necrosis or necrotic cell death. In this study, we first identified DIAPH3 as expressed protein tissues patients with pancreatic cancer, confirmed that promoted proliferation, anchorage‐independent growth invasion cells using overexpression interference experiments. Secondly, bioinformatics data mining showed potential proteins interacted were involved regulation. be incorporated into selenoprotein synthesis such TrxR1 GPX4, direct reduction hydroperoxides resist ferroptosis, respectively. Our following validation selenium content RPL6, ribosome subunit metabolism. addition, verified could down‐regulate cellular ROS level via up‐regulating expression. Finally, nude mice xenograft model experimental results demonstrate knock down decrease expression levels vivo. Collectively, our observations indicate progression activating TrxR1‐mediated antioxidant effects.

Language: Английский

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Formins in Human Disease

Cells, Journal Year: 2021, Volume and Issue: 10(10), P. 2554 - 2554

Published: Sept. 27, 2021

Almost 25 years have passed since a mutation of formin gene, DIAPH1, was identified as being responsible for human inherited disorder: form sensorineural hearing loss. Since then, our knowledge the links between formins and disease has deepened considerably. Mutations DIAPH1 six other genes (DAAM2, DIAPH2, DIAPH3, FMN2, INF2 FHOD3) been genetic cause variety disorders, including intellectual disability, renal disease, peripheral neuropathy, thrombocytopenia, primary ovarian insufficiency, loss cardiomyopathy. In addition, alterations in associated with pathological conditions, developmental defects affecting heart, nervous system kidney, aging-related diseases, cancer. This review summarizes most recent discoveries about involvement monogenic disorders especially cancer, which they associated. vitro results experiments modified animal models are discussed. Finally, we outline directions future research this field.

Language: Английский

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Actin regulators in cancer progression and metastases: From structure and function to cytoskeletal dynamics

International review of cell and molecular biology, Journal Year: 2020, Volume and Issue: unknown, P. 131 - 196

Published: Jan. 1, 2020

Language: Английский

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Targeting the NRF-2/RHOA/ROCK signaling pathway with a novel aziridonin, YD0514, to suppress breast cancer progression and lung metastasis

Cancer Letters, Journal Year: 2018, Volume and Issue: 424, P. 97 - 108

Published: March 23, 2018

Language: Английский

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Cucurbitacin B inhibits the migration and invasion of breast cancer cells by altering the biomechanical properties of cells

Phytotherapy Research, Journal Year: 2018, Volume and Issue: 33(3), P. 618 - 630

Published: Dec. 12, 2018

Changes in cellular biomechanical properties affect cell migration and invasion. The natural compound Cucurbitacin B (CuB) has potent anticancer activity; however, the mechanism underlying its inhibitory effect on breast cancer metastasis needs further study. Here, we showed that low-dose CuB inhibited adhesion altered viscoelasticity of cells, thereby, reducing deformability. In vitro vivo experiments proved effectively invasion cells. Further studies have found downregulated expression F-actin/vimentin/FAK/vinculin altering distribution reorganization cytoskeletal proteins signaling by Rho family GTPases RAC1/CDC42/RhoA downstream integrin. These findings indicate been proven to mediate cells through signaling, which improves mechanical deformation consequently inhibits

Language: Английский

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DIAPH3 promotes the tumorigenesis of lung adenocarcinoma

Experimental Cell Research, Journal Year: 2019, Volume and Issue: 385(1), P. 111662 - 111662

Published: Oct. 3, 2019

Language: Английский

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DIAPH3 is a prognostic biomarker and inhibit colorectal cancer progression through maintaining EGFR degradation

Cancer Medicine, Journal Year: 2022, Volume and Issue: 11(23), P. 4688 - 4702

Published: May 11, 2022

Actin cytoskeleton is connected with the processes of cell proliferation and migration in colorectal cancer (CRC). However, it unknown how to accomplish these adjustments CRC by actin genes (ACGs) here we investigated role hub prognosis-related ACGs-Diaphanous-related formin 3 (DIAPH3) CRC, as a potential, novel target.The ACGs gene set from Kyoto Encyclopedia Genes Genomes (KEGG) was used group patients select univariate multivariate Cox regression for constructing prognostic model. Next, tested ACGs- DIAPH3 expression clarified shRNA constructs KM12 SW480. Activation EGFR analyzed western blot immunofluorescence.The results showed that function significant factor related clinicopathological characteristics such T stage lymph node metastasis. A model constructed four has moderate intensity 1-year Survival (AUC = 0.71). And downregulated CRC. Knockdown could promote capacity In addition, DIAPH3-silenced cells increase phosphorylation inhibiting transportation lysosome.ACGs play tumor invasion have potential predict prognosis Prognosis-related might be new biomarker inhibit progression through maintaining degradation.

Language: Английский

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Adaptive Sparse Multi-Block PLS Discriminant Analysis: An Integrative Method for Identifying Key Biomarkers from Multi-Omics Data

Genes, Journal Year: 2023, Volume and Issue: 14(5), P. 961 - 961

Published: April 23, 2023

With the growing use of high-throughput technologies, multi-omics data containing various types high-dimensional omics is increasingly being generated to explore association between molecular mechanism host and diseases. In this study, we present an adaptive sparse multi-block partial least square discriminant analysis (asmbPLS-DA), extension our previous work, asmbPLS. This integrative approach identifies most relevant features across different while discriminating multiple disease outcome groups. We used simulation with scenarios a real dataset from TCGA project demonstrate that asmbPLS-DA can identify key biomarkers each type better biological relevance than existing competitive methods. Moreover, showed comparable performance in classification subjects terms status or phenotypes using integrated profiles, especially when combined other algorithms, such as linear random forest. have made R package called asmbPLS implements method publicly available on GitHub. Overall, achieved feature selection classification. believe be valuable tool for research.

Language: Английский

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Knockdown of DIAPH3 Inhibits the Proliferation of Cervical Cancer Cells through Inactivating mTOR Signaling Pathway

Journal of Oncology, Journal Year: 2021, Volume and Issue: 2021, P. 1 - 16

Published: Oct. 6, 2021

Cervical cancer (CC) ranks fourth for both incidence and mortality among females in worldwide. Therefore, it is urgent to explore new therapeutic diagnostic targets cervical cancer. Diaphanous-related formin 3 (DIAPH3) has been identified play crucial roles many malignant tumors. But its function potential mechanism CC remain largely unknown. In our study, DIAPH3 was frequently upregulated tissue samples increased expression of associated with poor overall survival according several databases. Through vitro vivo experiments, we found that decreased levels significantly inhibited the progression CC. The GSEA analysis western blot assay indicated mTOR signaling pathway. univariate multivariate Cox an independent prognosis risk factor TCGA-CESC. And confirmed clearly related tumor immune infiltrating cells (TIICs) by CIBERSORT TIMER Taken together, revealed plays as oncogene through pathway might be a prognostic biomarker

Language: Английский

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