Dysregulation of locus-specific repetitive elements in TCGA pan-cancers DOI Creative Commons
Chao Wang, Chun Liang

Опубликована: Окт. 23, 2024

Abstract Understanding the role of repetitive elements (REs) in cancer development is crucial for identifying novel biomarkers and therapeutic targets. This study investigated locus-specific dysregulation REs, including differential expression methylation across 12 TCGA types stratified by their genomic context ( i.e. , genic intergenic REs). We found uniquely dysregulated REs co-regulated with corresponding transcripts associated distinct biological functions different types. Uniquely were identified each type used to cluster sample Recurrently several types, genes up-regulated involved cell cycle processes those down-regulated extracellular matrix. Interestingly, 4 out 5 consistently all located intronic region TMEM252, a recently discovered tumor suppressor gene. TMEM252 was also 10 suggesting its potential importance wide range With DNA array data, we higher prevalence hypo-methylated most (10 12). Despite slight overlaps between differentially expressed methylated showed that negatively correlates some

Язык: Английский

Ononin inhibits triple-negative breast cancer lung metastasis by targeting the EGFR-mediated PI3K/Akt/mTOR pathway DOI
Kumar Ganesan, Cong Xu, Jianming Wu

и другие.

Science China Life Sciences, Год журнала: 2024, Номер 67(9), С. 1849 - 1866

Опубликована: Июнь 17, 2024

Язык: Английский

Процитировано

41
TMEM64 aggravates the malignant phenotype of glioma by activating the Wnt/β-catenin signaling pathway DOI Creative Commons
Hui Yang,

Hanyu Zhou,

Minjie Fu

и другие.

International Journal of Biological Macromolecules, Год журнала: 2024, Номер 260, С. 129332 - 129332

Опубликована: Янв. 15, 2024

Transmembrane protein 64 (TMEM64), a member of the family transmembrane protein, is an α-helical membrane protein. Its precise role in various types tumors, including glioma, unclear. This study used immunohistochemical (IHC) staining, western blotting, and quantitative reverse transcription polymerase chain reaction (qRT-PCR) techniques to show that TMEM64 expression was significantly higher glioma cells tissues compared normal tissues, respectively. Additionally, correlation between high grade as well worse prognosis found. enhanced cell proliferation tumorigenicity while inhibiting apoptosis vitro vivo, according loss- gain-of-function studies. Mechanistically, it discovered increased malignant phenotype gliomas by accelerating translocation β-catenin from cytoplasm nucleus, thereby activating Wnt/β-catenin signaling pathway. Stimulation with pathway activator CHIR-99021 successfully reversed glioma; however, these effects were inhibited upon silencing. inhibitor XAV-939 rescued which promoted overexpression. Our results provide novel prognostic biomarker potential treatment target for glioma.

Язык: Английский

Процитировано

6
Analyses of hypoxia-related risk factors and clinical relevance in breast cancer DOI Creative Commons
Yan Li, Haiyang Yu, Xinghua Han

и другие.

Frontiers in Oncology, Год журнала: 2024, Номер 14

Опубликована: Март 4, 2024

Hypoxia plays an important role in the heterogeneity, relapse, metastasis, and drug resistance of breast cancer. In this study, we explored hypoxia-related biological signatures different subtypes cancer identified key prognostic factors by bioinformatics methods. Based on The Cancer Genome Atlas (TCGA) Breast datasets, divided samples into immune-activated/suppressed populations single-sample gene set enrichment analysis (ssGSEA) then used hierarchical clustering to further identify hypoxic/non-hypoxic from immune-suppressed samples. A hypoxia related risk model was constructed. Nuclear factor interleukin-3 regulated (NFIL3), serpin family E member 1 (SERPINE1), FOS, biglycan (BGN), epidermal growth receptor (EGFR), sushi-repeat-containing protein, X-linked (SRPX) were as genes. Margin status, American Joint Committee (AJCC) stage, estrogen receptor/progesterone (ER/PR) NFIL3, SERPINE1, EGFR, score independent indicators for patients. 3- 5-year survival curves immunohistochemical staining microarray verified statistical significance feasibility our model. Among molecular types cancer, ER/PR+ HER2+ patients might have higher scores. ER/PR-negative demonstrated more activated immune-related pathways better response most anticancer agents. Our study revealed a novel potential feasible provide new perspectives individual treatment.

Язык: Английский

Процитировано

6
Potential therapeutic targets of the JAK2/STAT3 signaling pathway in triple-negative breast cancer DOI Creative Commons

Long Lin,

Xiangyu Fei,

Liucui Chen

и другие.

Frontiers in Oncology, Год журнала: 2024, Номер 14

Опубликована: Апрель 18, 2024

Triple-negative breast cancer (TNBC) poses a significant clinical challenge due to its propensity for metastasis and poor prognosis. TNBC evades the body's immune system recognition attack through various mechanisms, including Janus Kinase 2 (JAK2)/signal transducer activator of transcription 3 (STAT3) signaling pathway. This pathway, characterized by heightened activity in numerous solid tumors, exhibits pronounced activation specific subtypes. Consequently, targeting JAK2/STAT3 pathway emerges as promising precise therapeutic strategy TNBC. The signal transduction cascade predominantly involves receptor tyrosine kinases, kinase JAK2, factor STAT3. Ongoing preclinical studies research are actively investigating this potential target treatment. article comprehensively reviews investigations into treatment using small molecule compounds. review explores role therapeutics, evaluating benefits limitations active inhibitors proteolysis-targeting chimeras aim is facilitate development novel small-molecule compounds that effectively. Ultimately, work seeks contribute enhancing efficacy patients with

Язык: Английский

Процитировано

6
The molecular subtyping and precision medicine in triple-negative breast cancer---based on Fudan TNBC classification DOI Creative Commons

Lijuan Weng,

Jian‐Liang Zhou,

Shenchao Guo

и другие.

Cancer Cell International, Год журнала: 2024, Номер 24(1)

Опубликована: Март 30, 2024

Abstract Triple-negative breast cancer (TNBC) is widely recognized as the most aggressive form of cancer, occurring more frequently in younger patients and characterized by high heterogeneity, early distant metastases poor prognosis. Multiple treatment options have failed to achieve expected therapeutic effects due lack clear molecular targets. Based on genomics, transcriptomics metabolomics, multi-omics analysis further clarifies TNBC subtyping, which provides a greater understanding tumour heterogeneity targeted therapy sensitivity. For instance, luminal androgen receptor subtype (LAR) exhibits responsiveness anti-AR therapy, basal-like immune-suppressed (BLIS) tends benefit from poly (ADP-ribose) polymerase inhibitors (PARPis) anti-angiogenic therapy. The efficacy multi-dimensional combination holds immense importance guiding personalized precision medicine for TNBC. This review offers systematic overview recent FuDan subtyping its role instruction clinical

Язык: Английский

Процитировано

5
Epidermal growth factor receptor targeted photodynamic degrader to activate breast cancer immunity by intensifying immunogenic cell death and downregulating PD-L1 DOI

Keyan Zhang,

Jun‐Mei Nie,

Yeyang Wu

и другие.

Chemical Engineering Journal, Год журнала: 2025, Номер unknown, С. 160811 - 160811

Опубликована: Фев. 1, 2025

Язык: Английский

Процитировано

0
A breast cancer targeted photodynamic degrader to activate immunotherapy through EGFR degradation mediated PD-L1 downregulation DOI

Yuxuan Wei,

Zuxiao Chen,

Chu‐Yu Huang

и другие.

Chemical Engineering Journal, Год журнала: 2024, Номер 488, С. 150822 - 150822

Опубликована: Март 29, 2024

Язык: Английский

Процитировано

4
PDZK1 suppresses TNBC development and sensitizes TNBC cells to erlotinib via the EGFR pathway DOI Creative Commons

Yuanzhen Ma,

Zhiyu Fang,

Hongning Zhang

и другие.

Cell Death and Disease, Год журнала: 2024, Номер 15(3)

Опубликована: Апрель 11, 2024

Epidermal growth factor receptor (EGFR)-targeted drugs (erlotinib, etc.) are used to treat multiple types of tumours. EGFR is highly expressed in most triple-negative breast cancer (TNBC) patients. However, only a small proportion TNBC patients benefit from EGFR-targeted clinical trials, and the resistance mechanism unclear. Here, we found that PDZ domain containing 1 (PDZK1) downregulated erlotinib-resistant cells, suggesting PDZK1 downregulation related erlotinib TNBC. binds EGFR. Through this interaction, promotes degradation by enhancing binding c-Cbl inhibits phosphorylation hindering dimerisation. We also specifically tissues correlated with poor prognosis In vitro vivo functional assays showed suppressed development. Restoration expression or kinase inhibitor treatment reversed degree cell malignancy induced overexpression knockdown, respectively. sensitised cells both vivo. conclusion, significant prognostic for potential molecular therapeutic target reversing cells.

Язык: Английский

Процитировано

4
Mechanistic exploration of Traditional Chinese Medicine regulation on tumor immune microenvironment in the treatment of triple-negative breast cancer: based on CiteSpace and bioinformatics analysis DOI Creative Commons

Dandan Feng,

Dongqing Pu,

Juan Ren

и другие.

Frontiers in Immunology, Год журнала: 2025, Номер 15

Опубликована: Янв. 10, 2025

Triple-negative breast cancer (TNBC) is a highly aggressive subtype of cancer, characterized by frequent recurrence, metastasis, and poor survival outcomes despite chemotherapy-based treatments. This study aims to investigate the mechanisms which Traditional Chinese Medicine (TCM) modulates tumor immune microenvironment in TNBC, utilizing CiteSpace bioinformatics analysis. We employed analyze treatment hotspots key TCM formulations, followed analysis identify main active components, targets, associated pathways, their clinical implications TNBC treatment. highlighted including Sanhuang Decoction. Network pharmacology identified major bioactive components such as Mutatochrome, Physcion diglucoside, Procyanidin B-5,3'-O-gallate, gallic acid-3-O-(6'-O-galloyl)-glucoside, isomucronulatol-7,2'-di-O-glucosiole, with core targets Mitogen-Activated Protein Kinase 1 (MAPK1), Janus 2 (JAK2), Lymphocyte-specific protein tyrosine kinase (LCK). These were found be involved regulation, particularly modulation CD8+ CD4+ T cells. Additionally, improved recurrence-free (RFS) overall (OS) patients. The therapeutic effects primarily involve within microenvironment, through regulation

Язык: Английский

Процитировано

0
Overexpression of PLCG2 and TMEM38A inhibit tumor progression in clear cell renal cell carcinoma DOI Creative Commons
Yiqiao Zhao, Liang Yang, Xiaojie Bai

и другие.

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Янв. 25, 2025

Clear cell renal carcinoma is a prevalent urological malignancy, imposing substantial burdens on both patients and society. In our study, we used bioinformatics methods to select four putative target genes associated with EMT prognosis developed nomogram model which could accurately predicting 5-year patient survival rates. We further analyzed proteome single-cell data selected PLCG2 TMEM38A for the following experiments. Overexpression models of were generated in Caki-1 786-O lines using plasmids. The vitro experiments demonstrated that them exerted pro-apoptotic effects cells, inducing G2/M phase arrest, inhibiting proliferation, suppressing EMT. summary, identified potential tumor suppressor factors stratified ccRCC into high-risk low-risk groups based these factors. Furthermore, elucidated impact lines, offering novel avenues therapeutic exploration.

Язык: Английский

Процитировано

0