Clinical and Experimental Medicine, Journal Year: 2022, Volume and Issue: 23(5), P. 1393 - 1404
Published: Nov. 6, 2022
Language: Английский
Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2023, Volume and Issue: 1878(6), P. 188997 - 188997
Published: Oct. 12, 2023
Language: Английский
Citations
19
Aging, Journal Year: 2024, Volume and Issue: 16(2), P. 1781 - 1795
Published: Jan. 19, 2024
Objective: The aim of this paper is to mine ferroptosis genes associated with breast cancer based on bioinformatics and machine learning, perform in vitro functional validation. Methods: Transcriptional clinical data patients were downloaded from TCGA database ferroptosis-related obtained FerrDB database. Significant differentially expressed between tissues adjacent normal selected. Functional enrichment analysis was performed these genes. Four learning algorithms used identify key cancer. A multi-factor Cox regression construct a risk score model for the accuracy validated using Kaplan-Meier survival curve receiver operating characteristic (ROC) analysis. Finally, cell experiments conducted validate biological functions cells MCF-7, further confirming results. Results: total 52 significantly identified, which mainly enriched pathways, central carbon metabolism cancer, HIF-1 signaling pathway, NOD-like receptor pathway. Three (TXNIP, SLC2A1, ATF3) closely related occurrence, development, prognosis identified algorithms. constructed three showed that low-risk group better than high-risk (P < 0.001). ROC had good predictive ability. In reliability screening Downregulation SLC2A1 expression promoted suppressed tumor growth 0.01), while overexpression TXNIP or ATF3 same effect 0.01). Conclusion: This study are
Language: Английский
Citations
8
Journal for ImmunoTherapy of Cancer, Journal Year: 2024, Volume and Issue: 12(2), P. e008226 - e008226
Published: Feb. 1, 2024
Background Immune checkpoint inhibitors (ICIs) are the standard of care for metastatic renal cell carcinoma (RCC); however, most patients develop de novo or acquired resistance to ICIs. Oxidative phosphorylation (OXPHOS) has been rarely explored as a potential target correcting ICI resistance. Methods We systematically analyzed RNA sequencing and clinical data from CheckMate, JAVELIN Renal 101, NCT01358721 trials, clinicopathological 25 Tongji Hospital investigate relationship between OXPHOS The Ndufb8 -knockdown Renca line was derived determine effect on RCC immunotherapy in vivo. Results An analysis CheckMate series revealed that high levels risk factors with RCC, but affected by thevon Hippel-Lindau protein (VHL) hypoxia-inducible factor-1α status. This result is consistent correlation characteristics prognostic observations at our institute. Knockdown mitochondrial complex I subunit had no growth migration vitro, slowed down Among anti-programmed death ligand 1 (PD-L1)-treated BALB/c mice, sh tumors grew slower than shControl corresponding mice survived longer. Flow cytometry CD8 + T cells tumors, which were exposed lower degree hypoxia expressed less programmed death-1 (PD-1) T-cell immunoglobulin domain mucin 3 (TIM-3), secreted more interferon-γ after stimulation. Immunofluorescence demonstrated higher proportion these hypoxic area. Conclusions reliable predictor response pronounced lesions. generate tumor microenvironment inhibit function through oxidative metabolism, thereby leading
Language: Английский
Citations
8
Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(12)
Published: Dec. 1, 2023
Abstract Aurora-A kinase interacting protein 1 (AURKAIP1) has been proved to take an intermediary role in cancer by functioning as a negative regulator of kinase. However, it remains unclear whether and how AURKAIP1 itself would directly engage regulating malignancies. The expression levels were detected triple breast (TNBC) immunohistochemistry western blots. CCK8, colony formation assays nude mouse model conducted determine cell proliferation whereas transwell wound healing performed observe migration. interaction DEAD-box helicase 5 (DDX5) verified through co-immunoprecipitation successively From the results, we found that was explicitly upregulated TNBC, which positively associated with tumor size, lymph node metastases, pathological stage unfavorable prognosis. silencing markedly inhibited TNBC migration vitro vivo. interacted stabilized DDX5 preventing ubiquitination degradation, overexpression successfully reversed inhibition induced knockdown AURKAIP1. Consequently, suppressed activity Wnt/β-catenin signaling DDX5-dependent manner. Our study may primarily disclose molecular mechanism AURKAIP1/DDX5/β-catenin axis modulated progression, indicating might serve therapeutic target well TNBC-specific biomarker for
Language: Английский
Citations
15
Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(4)
Published: April 12, 2024
Radiotherapy effectiveness in breast cancer is limited by radioresistance. Nevertheless, the mechanisms behind radioresistance are not yet fully understood. RUVBL1 and RUVBL2, referred to as RUVBL1/2, crucial AAA+ ATPases that act co-chaperones connected cancer. Our research revealed RUVBL1, also known pontin/TIP49, excessively expressed MMTV-PyMT mouse models undergoing radiotherapy, which considered a murine spontaneous breast-tumor model. findings suggest enhances DNA damage repair cells both vitro vivo. Mechanistically, we discovered DTL, CDT2 or DCAF2, substrate adapter protein of CRL4, promotes ubiquitination facilitates its binding RUVBL2 transcription cofactor β-catenin. This interaction, turn, attenuates acetyltransferase Tat-interacting 60 (TIP60), comodulator nuclear receptors. Subsequently, ubiquitinated transcriptional regulation RUVBL1/2-β-catenin on genes associated with non-homologous end-joining (NHEJ) pathway. process TIP60-mediated H4K16 acetylation homologous recombination (HR) process. Expanding upon prior study's discoveries, exhibited DTL advances interosculation RUVBL1/2-β-catenin. And, it then regulates NHEJ pathway protein. Resulting an elevated resistance radiation therapy. From aforementioned, evident targeting DTL-RUVBL1/2-β-catenin provides potential radiosensitization approach when treating
Language: Английский
Citations
6
Cancer and Metastasis Reviews, Journal Year: 2024, Volume and Issue: 43(3), P. 889 - 918
Published: Feb. 27, 2024
Language: Английский
Citations
5
International Journal of Nanomedicine, Journal Year: 2024, Volume and Issue: Volume 19, P. 3387 - 3404
Published: April 1, 2024
Abstract: Cancer immunotherapy has emerged as a novel therapeutic approach against tumors, with immune checkpoint inhibitors (ICIs) making significant clinical practice. The traditional ICIs, PD-1 and PD-L1, augment the cytotoxic function of T cells through inhibition tumor evasion pathways, ultimately leading to initiation an antitumor response. However, implementation ICIs encounters obstacles stemming from existence immunosuppressive microenvironment inadequate infiltration CD8 + cells. Considerable attention been directed towards advancing immunogenic cell death (ICD) potential solution counteract microenvironment. This holds promise in transforming "cold" tumors into "hot" that exhibit responsiveness antitumor. By combining ICD synergistic response can be achieved. combination inducers PD-1/PD-L1 is hindered by issues such poor targeting uncontrolled drug release. An advantageous presented stimulus-responsive nanocarrier integrating physicochemical properties inhibitors, facilitating precise delivery specific tissues for optimal therapy. Moreover, these nanocarriers leverage distinct features accomplish controlled release regulate kinetics delivery. article aims investigate advancement co-delivery utilizing inhibitors. Special focus dedicated exploring advantages recent advancements this system enabling inducers. molecular mechanisms are concisely summarized. In conclusion, we examine research prospects challenges could greatly enhance immunotherapeutic approaches cancer treatment. Keywords: therapy, death, co-delivery, immune-checkpoint
Language: Английский
Citations
5
Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12
Published: Nov. 22, 2021
Chronic inflammation is a prerequisite for the development of cancers. Here, we present framework novel theory termed as Cancer Evolution-Development (Cancer Evo-Dev) based on current understanding inflammation-related carcinogenesis, especially hepatocarcinogenesis induced by chronic infection with hepatitis B virus. The interaction between genetic predispositions and environmental exposures, such viral infection, maintains non-resolving inflammation. Pollution, metabolic syndrome, physical inactivity, ageing, adverse psychosocial exposure also increase risk cancer via inducing low-grade smoldering Under microenvironment inflammation, pro-inflammatory factors facilitate generation somatic mutations imbalance mutagenic forces cytidine deaminases mutation-correcting including uracil-DNA glycosylase. Most cells mutated viruses are eliminated in survival competition. Only small percentage survive, adapt to hostile environment, retro-differentiate, function cancer-initiating altering signaling pathways. These acquire stem-ness, reprogram patterns, affect microenvironment. carcinogenic process follows law "mutation-selection-adaptation". activity reduces levels upregulating numbers NK lymphocytes lengthening leukocyte telomere; downregulating proinflammatory cytokines interleukin-6 senescent aged population. Anti-inflammation medication occurrence recurrence Targeting stemness pathways might lead eradication. Evo-Dev not only helps understand mechanisms which promotes cancers, but lays foundation effective prophylaxis targeted therapy various
Language: Английский
Citations
31
Cancers, Journal Year: 2022, Volume and Issue: 14(18), P. 4518 - 4518
Published: Sept. 17, 2022
Hypoxia is a common feature associated with many types of cancer. The activity the hypoxia-inducible factors (HIFs), critical element response and adaptation to hypoxia, enhances cancer hallmarks such as suppression immune response, altered metabolism, angiogenesis, invasion, metastasis, more. HIF-1α HIF-2α isoforms show similar regulation characteristics, although they are active in different hypoxia can or even opposite effects. Breast cancers present several unique ways non-canonical induction, not limited itself. This review summarizes effects HIFs activation breast cancer, where areas evasion cell survival death, stem cells, hormone receptors status have been covered. differences between their impacts given special attention. paper also discusses perspectives on using targets anticancer therapy, current knowledge acquired molecular studies.
Language: Английский
Citations
22
Frontiers in Genetics, Journal Year: 2022, Volume and Issue: 13
Published: June 24, 2022
DNA methylation is treated as an important epigenetic mark in various biological activities. In the past, a large number of articles focused on 5 mC while lacking attention to N6-methyladenine (6 mA). The presence 6 mA modification was previously discovered only prokaryotes. Recently, with development detection technologies, has been found several eukaryotes, including protozoans, metazoans, plants, and fungi. importance prokaryotes single-celled eukaryotes widely accepted. However, due incredibly low density restrictions prevalence its role processes eukaryotic organisms are highly debated. this review, we first summarize advantages disadvantages methods. Then, conclude existing reports organisms. Next, highlight possible methyltransferases, demethylases, recognition proteins mA. addition, functions eukaryotes. Last but not least, our point view put forward problems that need further research.
Language: Английский
Citations
20