A novel axis of circKIF4A-miR-637-STAT3 promotes brain metastasis in triple-negative breast cancer

Cancer Letters, Journal Year: 2023, Volume and Issue: 581, P. 216508 - 216508

Published: Nov. 28, 2023

Among patients with triple-negative breast cancer (TNBC), distant metastasis is the leading cause of death. Our previous studies have shown that TNBC progression greatly facilitated by circKIF4A, but uncertainty remains regarding its role in brain and molecular mechanism. In this study, we found notable upregulation circKIF4A cell lines metastases. Inhibition impaired ability to proliferate, migrate, metastasis. Luciferase reporter assays confirmed competed for binding miR-637 STAT3 3’ UTR. Western blot analysis revealed inhibition decreased p62 expression, while increased LC3B-II/LC3B–I ratio expression Beclin, indicating downregulation induced autophagy competing miR-637. By employing a competitive endogenous RNA (ceRNA) mechanism, circKIF4A-miR-637-STAT3 axis coordinates TNBC. can therefore be used as prognostic biomarker therapeutic target.

Language: Английский

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Nano-drug delivery system targeting tumor microenvironment: A prospective strategy for melanoma treatment

Cancer Letters, Journal Year: 2023, Volume and Issue: 574, P. 216397 - 216397

Published: Sept. 18, 2023

Language: Английский

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Nasopharyngeal carcinoma: current views on the tumor microenvironment's impact on drug resistance and clinical outcomes

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: Jan. 22, 2024

Abstract The incidence of nasopharyngeal carcinoma (NPC) exhibits significant variations across different ethnic groups and geographical regions, with Southeast Asia North Africa being endemic areas. Of note, Epstein-Barr virus (EBV) infection is closely associated almost all the undifferentiated NPC cases. Over past three decades, radiation therapy chemotherapy have formed cornerstone treatment. However, recent advancements in immunotherapy introduced a range promising approaches for managing NPC. In light these developments, it has become evident that deeper understanding tumor microenvironment (TME) crucial. TME serves dual function, acting as promoter tumorigenesis while also orchestrating immunosuppression, thereby facilitating cancer progression enabling immune evasion. Consequently, comprehensive comprehension its intricate involvement initiation, progression, metastasis imperative development effective anticancer drugs. Moreover, given complexity inter-patient heterogeneity, personalized treatment should be designed to maximize therapeutic efficacy circumvent drug resistance. This review aims provide an in-depth exploration within context EBV-induced NPC, particular emphasis on pivotal role regulating intercellular communication shaping responses. Additionally, offers concise summary resistance mechanisms potential strategies their reversal, specifically relation chemoradiation therapy, targeted immunotherapy. Furthermore, advances clinical trials pertaining are discussed.

Language: Английский

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Biomarkers for diagnosis and therapeutic options in hepatocellular carcinoma

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: Sept. 6, 2024

Language: Английский

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crVDAC3 alleviates ferroptosis by impeding HSPB1 ubiquitination and confers trastuzumab deruxtecan resistance in HER2-low breast cancer

Drug Resistance Updates, Journal Year: 2024, Volume and Issue: 77, P. 101126 - 101126

Published: Aug. 6, 2024

Language: Английский

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Exosomal circRNAs: Novel biomarkers and therapeutic targets for urinary tumors

Cancer Letters, Journal Year: 2024, Volume and Issue: 588, P. 216759 - 216759

Published: Feb. 28, 2024

Language: Английский

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Causal relationship between immune cells and prostate cancer: a Mendelian randomization study

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: March 19, 2024

Introduction: Despite the abundance of research indicating participation immune cells in prostate cancer development, establishing a definitive cause-and-effect relationship has proven to be difficult undertaking. Methods: This study employs Mendelian randomization (MR), leveraging genetic variables related from publicly available genome-wide association studies (GWAS), investigate this association. The primary analytical method used is inverse variance weighting (IVW) analysis. Comprehensive sensitivity analyses were conducted assess heterogeneity and horizontal pleiotropy results. Results: identifies four cell traits as causally contributing risk, including CD127- CD8+ T %CD8+ (OR = 1.0042, 95%CI:1.0011–1.0073, p 0.0077), CD45RA on CD39+ resting CD4 regulatory 1.0029, 95%CI:1.0008–1.0050, 0.0065), CD62L− Dendritic Cell Absolute Count 1.0016; 95%CI:1.0005–1.0026; 0.0039), CX3CR1 CD14+ CD16− monocyte 1.0024, 95%CI:1.0007–1.0040, 0.0060). Additionally, two are identified protective factors: 0.9975, 95%CI:0.9958–0.9992, 0.0047), FSC-A plasmacytoid 0.9983, 95%CI:0.9970–0.9995, 0.0070). Sensitivity indicated no pleiotropy. Discussion: Our MR provide evidence for causal between cancer, holding implications clinical diagnosis treatment.

Language: Английский

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CircPDIA3/miR-449a/XBP1 feedback loop curbs pyroptosis by inhibiting palmitoylation of the GSDME-C domain to induce chemoresistance of colorectal cancer

Drug Resistance Updates, Journal Year: 2024, Volume and Issue: 76, P. 101097 - 101097

Published: May 28, 2024

Although oxaliplatin (OXA) is widely used in the frontline treatment of colorectal cancer (CRC), CRC recurrence commonly observed due to OXA resistance. resistance associated with a number factors, including abnormal regulation pyroptosis. It therefore important elucidate regulatory mechanism underlying Here, we identified that circular RNA circPDIA3 played an role chemoresistance CRC. CircPDIA3 could induce by inhibiting pyroptosis both vitro and vivo. Mechanistically, RIP, pull-down co-IP assays revealed directly bonded GSDME-C domain, subsequently enhanced autoinhibitory effect domain through blocking palmitoylation ZDHHC3 ZDHHC17, thereby restraining Additionally, it was found circPDIA3/miR-449a/XBP1 positive feedback loop increased expression chemoresistance. Furthermore, our clinical data patient-derived tumor xenograft (PDX) models supported association development patients. Taken together, findings demonstrated promote amplifying inhibition This study provides novel insights into circRNA regulating providing potential therapeutic target for reversing

Language: Английский

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The role of cancer-associated fibroblasts and exosomal miRNAs-mediated intercellular communication in the tumor microenvironment and the biology of carcinogenesis: a systematic review

Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: Aug. 26, 2024

Abstract CAFs (cancer-associated fibroblasts) are highly flexible cells of the cancer microenvironment. They produce extracellular matrix (ECM) constituents that form structure tumor stroma but also a source metabolites, growth factors, chemokines, and exosomes impact every aspect tumor, including its response to treatment. It is believed exosomal miRNAs facilitate intercellular signaling, which essential for development cancer. The role in microenvironment (TME) carcinogenesis reviewed this paper. preferred reporting items systematic reviews meta-analyses (PRISMA) 2020 guidelines were used perform review. Several databases, Web Science, Medline, Embase, Cochrane Library, Scopus, searched using following keywords: CAFs, CAF, cancer-associated fibroblasts, stromal miRNA, miRNAs, exosome similar terms. We identified studies investigating TME their carcinogenesis. A total 12,572 papers identified. After removing duplicates ( n = 3803), 8774 articles screened by title abstract. Of these, 421 excluded from further analysis. has been reported if not functioning correctly, may influence secretory phenotype tip contribute increased invasiveness, spread, decreased treatment efficacy, poorer prognosis. Under influence, normal fibroblasts (NFs) transformed into CAFs. Furthermore, they participate metabolic reprogramming, allows fast proliferation cell population, adaptation growing energy demands, capacity avoid immune system identification.

Language: Английский

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IL-12-Overexpressed Nanoparticles Suppress the Proliferation of Melanoma Through Inducing ICD and Activating DC, CD8+ T, and CD4+ T Cells

International Journal of Nanomedicine, Journal Year: 2024, Volume and Issue: Volume 19, P. 2755 - 2772

Published: March 1, 2024

Purpose: The drug resistance and low response rates of immunotherapy limit its application. This study aimed to construct a new nanoparticle (CaCO 3 -polydopamine-polyethylenimine, CPP) effectively deliver interleukin-12 (IL-12) suppress cancer progress through immunotherapy. Methods: size distribution CPP zeta potential were measured using Malvern Zetasizer Nano-ZS90. morphology electrophoresis tentative delay analyzed JEM-1400 transmission electron microscope an ultraviolet spectrophotometer, respectively. Cell proliferation was by MTT assay. Proteins Western blot. IL-12 HMGB1 levels estimated ELISA kits. Live/dead staining assay performed Calcein-AM/PI kit. ATP production detected xenografts in vivo C57BL/6 mice. CD80 + /CD86 , CD3 /CD4 /CD8 flow cytometry. Results: could express EGFP or increase ROS levels. Laser treatment promoted CPP-IL-12 induced the number dead apoptotic cell. laser further enhance CALR extracellular decrease intracellular levels, indicating that it may induce immunogenic cell death (ICD). tumors weights laser-treated mice significantly reduced than controls. expression, expression DC from lymph glands, T cells spleen increased CPP-IL-12-treated compared with granzyme B, IFN-γ, TNF-α serum increased. Interestingly, local back inhibit growth distant untreated tumor. Conclusion: novel overexpress melanoma achieve inducing ICD, activating CD4 cell, enhancing function tumor-reactive CD8 cells. Keywords: immunotherapy, CaCO nanoparticle, interleukin-12, death, tumor therapy

Language: Английский

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