Low expression of miR-7-5p promotes resistance to radiotherapy in lung cancer through direct upregulation of PKP2 expression DOI Creative Commons
Fan Zhang,

Jiaxue Yang,

Xiafei Qiu

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 8, 2024

Abstract Purpose Lung cancer remains a significant global health challenge, with advanced stages often limiting surgical options and necessitating systemic therapies like radiotherapy. Resistance to radiotherapy frequently undermines treatment efficacy. This study explores the role of miR-7-5p in modulating plakophilin-2 (PKP2) expression its impact on radiosensitivity non-small cell lung (NSCLC) cells. Methods Using clonogenic assays, CCK-8 immunofluorescence staining, Western blotting, reporter gene we assessed effects overexpression inhibition A549 NSCLC Results show that enhances by increasing DNA damage (evidenced higher γ-H2AX foci) inhibiting non-homologous end joining (NHEJ) repair. Bioinformatics experimental validation identified PKP2 as direct target miR-7-5p. Overexpression mitigates radiosensitizing miR-7-5p, confirming miR-7-5p/PKP2 axis's regulating radiosensitivity. Conclusion work highlights potential targeting pathway overcome resistance NSCLC, offering promising therapeutic approach enhance outcomes.

Language: Английский

NR5A2 gene affects the overall survival of LUAD patients by regulating the activity of CSCs through SNP pathway by OCLR algorithm and immune score DOI Creative Commons
Liusheng Wu, Xiaofan Chen, Qi Zeng

et al.

Heliyon, Journal Year: 2024, Volume and Issue: 10(7), P. e28282 - e28282

Published: March 28, 2024

Differentially expressed genes (DEGs) in lung adenocarcinoma (LUAD) tumor stem cells were screened, and the biological characteristics of

Language: Английский

Citations

36
Harnessing the tumor microenvironment: targeted cancer therapies through modulation of epithelial-mesenchymal transition DOI Creative Commons
Antonino Glaviano,

Hannah Lau,

Lukas M. Carter

et al.

Journal of Hematology & Oncology, Journal Year: 2025, Volume and Issue: 18(1)

Published: Jan. 13, 2025

The tumor microenvironment (TME) is integral to cancer progression, impacting metastasis and treatment response. It consists of diverse cell types, extracellular matrix components, signaling molecules that interact promote growth therapeutic resistance. Elucidating the intricate interactions between cells TME crucial in understanding progression challenges. A critical process induced by epithelial-mesenchymal transition (EMT), wherein epithelial acquire mesenchymal traits, which enhance their motility invasiveness progression. By targeting various components TME, novel investigational strategies aim disrupt TME's contribution EMT, thereby improving efficacy, addressing resistance, offering a nuanced approach therapy. This review scrutinizes key players emphasizing avenues therapeutically components. Moreover, article discusses implications for resistance mechanisms highlights current toward modulation along with potential caveats.

Language: Английский

Citations

12
Construction of a novel radioresistance-related signature for prediction of prognosis, immune microenvironment and anti-tumour drug sensitivity in non-small cell lung cancer DOI Creative Commons
Yanliang Chen, Chan Zhou, Xiaoqiao Zhang

et al.

Annals of Medicine, Journal Year: 2025, Volume and Issue: 57(1)

Published: Jan. 10, 2025

Background Non-small cell lung cancer (NSCLC) is a fatal disease, and radioresistance an important factor leading to treatment failure disease progression. The objective of this research was detect radioresistance-related genes (RRRGs) with prognostic value in NSCLC.

Language: Английский

Citations

1
Comparative analysis of pediatric SHH medulloblastoma DAOY spheres and adherent monolayers: implications for medulloblastoma research DOI Creative Commons

Jana Klementová,

Šárka Jarošová,

Irina Danilová

et al.

Cancer Cell International, Journal Year: 2025, Volume and Issue: 25(1)

Published: Jan. 22, 2025

Medulloblastoma, the most prevalent brain tumor among children, requires a comprehensive understanding of its cellular characteristics for effective research and treatment. In this study, we focused on DAOY, permanent cell line medulloblastoma, investigated unique properties DAOY cells when cultured as floating multicellular aggregates called spheres, opposed to adherent monolayers. Through our analysis, identified distinct associated with spheres. Our findings demonstrate that spheres express markers both neural stem cells, such CD133 (PROM1), differentiated neurons, exemplified by MAP2. Additionally, investigation revealed spheres-derived exhibit heightened resistance ionizing radiation compared cells. Consequently, results indicate caution is advised interpreting experimental obtained from cultures extrapolating them in vivo situations.

Language: Английский

Citations

1
Tumor-associated macrophages in non-small-cell lung cancer: From treatment resistance mechanisms to therapeutic targets DOI Creative Commons
Zhenjun Huang,

Ziqi Xiao,

Li‐Qing Yu

et al.

Critical Reviews in Oncology/Hematology, Journal Year: 2024, Volume and Issue: 196, P. 104284 - 104284

Published: Feb. 2, 2024

Non-small cell lung cancer (NSCLC) remains one of the leading causes cancer-related deaths worldwide. Different treatment approaches are typically employed based on stage NSCLC. Common clinical methods include surgical resection, drug therapy, and radiation therapy. However, with introduction utilization immune checkpoint inhibitors, has entered a new era, completely revolutionizing landscape for various cancers significantly improving overall patient survival. Concurrently, resistance often poses critical challenge, many patients experiencing disease progression following an initial response due to resistance. Increasing evidence suggests that tumor microenvironment (TME) plays pivotal role in Tumor-associated macrophages (TAMs) within TME can promote NSCLC by secreting cytokines activating signaling pathways, interacting other cells. Therefore, this article will focus elucidating key mechanisms TAMs analyze how targeting reduce levels NSCLC, providing comprehensive understanding principles overcome

Language: Английский

Citations

7
GRHL3 drives radiotherapy resistance and blocks the anti-tumor response of NK and CD4+ T cells in lung squamous cell carcinoma via RNF2 DOI
Haijun Wang, Changjiang Liu, Chao Jiang

et al.

Biochemical Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 116784 - 116784

Published: Jan. 1, 2025

Language: Английский

Citations

0
JNK Inhibition Overcomes Resistance of Metastatic Tetraploid Cancer Cells to Irradiation-Induced Apoptosis DOI Open Access
Mohamed Jèmaà, Nouha Setti Boubaker, Nesrine Kerkeni

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 1209 - 1209

Published: Jan. 30, 2025

Tetraploidy is a condition in which the entire set of chromosomes doubles, most often due to errors during cell division. can lead genomic instability and significant consequences, particular metastasis treatment failure tumours, including radiotherapy. The development new strategies sensitise these cells great importance. In our study, we investigated vitro combination chemical with kinase inhibitor SP600125 irradiation on diploid versus metastatic tetraploid RKO colon cancer clones. We assessed mitochondrial transmembrane potential, cycle subG1 population by flow cytometry performed clonogenic assays evaluate sensitivity. found that overcomes resistance To identify main pathway involved sensitivity, screened Harvard Medical School KINOMEscan library gene ontology biological process analysis. major kinases inhibited were ANKK1, BIKE, IKKA, JNK1, MP2K3, MP2K4, MKNK2, MYLK, PLK4, RPS6KA4(Kin,Dom,1), MYLK4 TTK, pathways clone sensitivity DNA damage repair, radiation apoptosis, through JNK inhibition. Finally, finding was combined radiotherapy reduced treatment, essentially inhibiting pathway. This result supports promising anti-cancer strategy overcome irradiation.

Language: Английский

Citations

0
Unveiling Novel Targets in Lung Tumors for Enhanced Radiotherapy Efficacy: A Comprehensive Review DOI Open Access

Faris Anad Muhammad,

Ayat Hussein Adhab,

Morug Salih Mahdi

et al.

Journal of Biochemical and Molecular Toxicology, Journal Year: 2025, Volume and Issue: 39(3)

Published: Feb. 23, 2025

ABSTRACT Radiotherapy is a cornerstone of lung cancer management, though its efficacy frequently undermined by intrinsic and acquired radioresistance. This review examines the complexity tumors, highlighting their potential as reservoir novel targets for radiosensitization. Ionizing radiation (IR) primarily exerts effects through oxidative damage DNA double‐strand breaks (DSBs). Lung cells, however, develop mutations that enhance response (DDR) suppress cell death pathways. Additionally, interactions between tumor cells microenvironment (TME) components—including immune stromal molecular mediators such cytokines, chemokines, growth factors—contribute to resistance against IR. Understanding these intricate relationships reveals improve radiotherapy outcomes. Promising include DDR pathways, immunosuppressive molecules, hypoxia, proangiogenic mediators, other key signaling discusses emerging strategies, combining with immunomodulators, hypoxia inhibitors, DDR‐targeting agents, innovative approaches. By offering comprehensive analysis TME, this underscores opportunities effectiveness targeted radiosensitization strategies.

Language: Английский

Citations

0
Genomic and demographic landscape of non-small cell lung cancer within an ethnically-diverse population – The implications for radiation oncology and personalised medicine DOI Creative Commons
Matthew C. Knox, Nader Aryamanesh, Lee Marshall

et al.

The Royal College of Radiologists Open, Journal Year: 2025, Volume and Issue: 3, P. 100341 - 100341

Published: Jan. 1, 2025

Language: Английский

Citations

0
Growth Hormone-Releasing Hormone Antagonists Increase Radiosensitivity in Non-Small Cell Lung Cancer Cells DOI Open Access
Iacopo Gesmundo, Francesca Pedrolli, F.R. Giglioli

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 3267 - 3267

Published: April 1, 2025

Growth hormone-releasing hormone (GHRH) antagonists exert antitumor functions in different experimental cancers. However, their role combination with radiotherapy non-small cell lung cancer (NSCLC) remains unknown. Therefore, we investigated the radiosensitizing effect of GHRH NSCLC. A549 and H522 NSCLC lines were exposed to ionizing radiation (IR) MIA-602 MIA-690, either individually or combination. Cell viability proliferation evaluated by MTT, BrdU, flow cytofluorimetry, clonogenic assays; gene protein expression, signaling pathways, apoptosis analyzed real-time PCR, Western blot, annexin staining, caspase-3 assay. showed effects alone potentiated IR-induced inhibition proliferation. The MIA-690 IR decreased expression receptor, its oncogenic splice variant 1, IGF1 mRNA levels. Additionally, cycle inhibitors proapoptotic markers upregulated, whereas cyclins, MYC, antiapoptotic Bcl-2 downregulated. Radioresistance was prevented which also blunted epithelial-mesenchymal transition enhancing E-cadherin reducing mesenchymal, oxidative, proangiogenic effectors. Finally, both enhanced radiosensitivity primary human cells. These findings highlight potential as radiosensitizers treatment.

Language: Английский

Citations

0