Cancer-associated fibroblasts drive colorectal cancer cell progression through exosomal miR-20a-5p-mediated targeting of PTEN and stimulating interleukin-6 production DOI Creative Commons

Mahsa Ghofrani-Shahpar,

Katayoon Pakravan,

Ehsan Razmara

et al.

BMC Cancer, Journal Year: 2024, Volume and Issue: 24(1)

Published: April 1, 2024

Abstract Background This study evaluated the clinical relevance of a set five serum-derived circulating microRNAs (miRNAs) in colorectal cancer (CRC). Additionally, we investigated role miR-20a-5p released by exosomes derived from cancer-associated fibroblasts (CAFs) context CRC. Methods The expression levels miRNAs (miR-20a-5p, miR-122-5p, miR-139-3p, miR-143-5p, and miR-193a-5p) were quantified real-time quantitative PCR (RT-qPCR), their associations with clinicopathological characteristics CRC patients assessed. diagnostic accuracy these was determined through Receiver Operating Characteristic (ROC) curve analysis. CAFs normal (NFs) isolated tissue samples, subsequently, cells meticulously characterized using electron microscopy Western blotting. cellular internalization fluorescent-labeled visualized confocal microscopy. Gain- loss-of-function experiments conducted to elucidate oncogenic transferred progression. underlying mechanisms uncovered luciferase reporter assay, blotting, enzyme-linked immunosorbent assays, as well proliferation migration assays. Results miR-122-5p significantly higher positively correlated advanced stages tumorigenesis lymph node metastasis (LNM). In contrast, miR-193a-5p down-regulated associated early tumorigenesis. Except for they showed negative correlation LNM status. Among candidate miRNAs, elevated observed both exosomal fractions CAFs. Our findings indicated that induces EMT markers, partly targeting PTEN. Exosomal miR-20a secreted emerged key factor enhancing cells. inhibition impaired proliferative migratory potential CAF-derived SW480 cells, suggesting effects are mediated transfer miR-20a. Furthermore , originating induced increased nuclear translocation NF-kB p65 transcription leading interleukin-6 (IL-6) production. Conclusions We established non-invasive biomarker diagnosis. our shed light on intricate underpinning impacts underscore pivotal

Language: Английский

The roles of proteases in prostate cancer DOI Creative Commons
Hannu Koistinen,

Ruusu‐Maaria Kovanen,

Morley D. Hollenberg

et al.

IUBMB Life, Journal Year: 2023, Volume and Issue: 75(6), P. 493 - 513

Published: Jan. 4, 2023

Since the proposition of pro-invasive activity proteolytic enzymes over 70 years ago, several roles for proteases in cancer progression have been established. About half 473 active human are expressed prostate and many most well-characterized members this enzyme family regulated by androgens, hormones essential development cancer. Most notably, kallikrein-related peptidases, including KLK3 (prostate-specific antigen, PSA), well-known marker, type II transmembrane serine proteases, such as TMPRSS2 matriptase, extensively studied found to promote progression. Recent findings also suggest a critical role advanced aggressive castration-resistant (CRPC). Perhaps intriguing evidence comes from studies showing that protease-activated proteins, Notch CDCP1, associated with CRPC. Here, we review cancer, special focus on their regulation androgens.

Language: Английский

Citations

21
Tumor microenvironment responsive metal nanoparticles in cancer immunotherapy DOI Creative Commons

Rou Yang,

Lu Chen,

Yiling Wang

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: July 27, 2023

Malignant tumors have a unique tumor microenvironment (TME), which includes mild acidity, hypoxia, overexpressed reactive oxygen species (ROS), and high glutathione (GSH) levels, among others. Recently, TME regulation approaches attracted widespread attention in cancer immunotherapy. Nanoparticles as drug delivery systems ability to modulate the hydrophilicity of drugs affect uptake efflux tumor. Especially, metal nanoparticles been extensive applied for immunotherapy due their physical properties elaborate design. However, potential deficiencies low biodegradability, toxicity treatment side effects restrict clinical application. In this review, we briefly introduce feature characteristics recent advances responsive addition, could be combined with other treatments, such chemotherapy, radiotherapy photodynamic therapy also is presented. Finally, challenges outlook improving antitumor efficiency, effect risks has discussed.

Language: Английский

Citations

21
THBS1-Mediated Degradation of Collagen via the PI3K/AKT Pathway Facilitates the Metastasis and Poor Prognosis of OSCC DOI Open Access

Zhihao Wen,

Yuxiao Zhang,

Xiangyao Wang

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(17), P. 13312 - 13312

Published: Aug. 28, 2023

Oral squamous cell carcinoma (OSCC) is a prevalent form of malignant tumor, characterized by persistently high incidence and mortality rate. The extracellular matrix (ECM) plays crucial role in the initiation, progression, diverse biological behaviors OSCC, facilitated mechanisms such as providing structural support, promoting migration invasion, regulating morphology, modulating signal transduction. This study investigated involvement ECM-related genes, particularly THBS1, prognosis cellular behavior OSCC. analysis gene data from OSCC samples identified 165 differentially expressed genes forming two clusters with distinct prognostic outcomes. Seventeen showed significant correlation survival. Experimental methods were employed to demonstrate impact THBS1 on proliferation, migration, ECM degradation cells. A risk-prediction model utilizing four demonstrated predictive value overall exhibited enrichment PI3K/AKT pathway, indicating its potential In conclusion, this observed verified that have influence prognosis, behavior, immunotherapy These findings hold implications for enhancing survival outcomes guidance precise treatment

Language: Английский

Citations

17
Stimuli-Responsive Polymeric Nanomedicine for Enhanced Cancer Immunotherapy DOI
Chan Ho Kim, Kyu Eun Lee, Hyewon Ko

et al.

Chemistry of Materials, Journal Year: 2024, Volume and Issue: 36(3), P. 1088 - 1112

Published: Jan. 29, 2024

Cancer immunotherapy, aimed at reinvigorating the immune system to induce a lasting anticancer response, has emerged as promising approach for counteracting evasive tactics of cancer cells. This study delves into innovative realm stimuli-responsive polymeric nanomedicines in context immunotherapy. By capitalizing on intricate landscape tumor microenvironment (TME), which orchestrates suppression and progression, offer tailored strategy enhance therapeutic interventions. The aberrant features TME, include factors such low pH, inflammation, oxidative stress, enzyme overexpression, serve triggers intelligent delivery systems facilitated by functional polymers. dynamic potential overcome challenges faced traditional nanoparticle-based immunotherapy techniques, presenting platform precisely optimize drug within locale. As synergistic interaction between TME unfolds, novel horizon emerges advance efficacy while mitigating its associated limitations.

Language: Английский

Citations

8
Cancer-associated fibroblasts drive colorectal cancer cell progression through exosomal miR-20a-5p-mediated targeting of PTEN and stimulating interleukin-6 production DOI Creative Commons

Mahsa Ghofrani-Shahpar,

Katayoon Pakravan,

Ehsan Razmara

et al.

BMC Cancer, Journal Year: 2024, Volume and Issue: 24(1)

Published: April 1, 2024

Abstract Background This study evaluated the clinical relevance of a set five serum-derived circulating microRNAs (miRNAs) in colorectal cancer (CRC). Additionally, we investigated role miR-20a-5p released by exosomes derived from cancer-associated fibroblasts (CAFs) context CRC. Methods The expression levels miRNAs (miR-20a-5p, miR-122-5p, miR-139-3p, miR-143-5p, and miR-193a-5p) were quantified real-time quantitative PCR (RT-qPCR), their associations with clinicopathological characteristics CRC patients assessed. diagnostic accuracy these was determined through Receiver Operating Characteristic (ROC) curve analysis. CAFs normal (NFs) isolated tissue samples, subsequently, cells meticulously characterized using electron microscopy Western blotting. cellular internalization fluorescent-labeled visualized confocal microscopy. Gain- loss-of-function experiments conducted to elucidate oncogenic transferred progression. underlying mechanisms uncovered luciferase reporter assay, blotting, enzyme-linked immunosorbent assays, as well proliferation migration assays. Results miR-122-5p significantly higher positively correlated advanced stages tumorigenesis lymph node metastasis (LNM). In contrast, miR-193a-5p down-regulated associated early tumorigenesis. Except for they showed negative correlation LNM status. Among candidate miRNAs, elevated observed both exosomal fractions CAFs. Our findings indicated that induces EMT markers, partly targeting PTEN. Exosomal miR-20a secreted emerged key factor enhancing cells. inhibition impaired proliferative migratory potential CAF-derived SW480 cells, suggesting effects are mediated transfer miR-20a. Furthermore , originating induced increased nuclear translocation NF-kB p65 transcription leading interleukin-6 (IL-6) production. Conclusions We established non-invasive biomarker diagnosis. our shed light on intricate underpinning impacts underscore pivotal

Language: Английский

Citations

8