Cancers
·
2023
·Vol. 15
·期 6
·1724
·
IF 5.2
Khalil Ur Rahman,Shuo Yang,Nasir Azam,Zhen Yuan,Jiawen Yu,Chunhui Zhao,Bin Feng
Simple SummaryBreast cancer is a disease that begins in the cells of the breast. Although it is most common in women, it can also occur in men, though this is rare. Early detection and treatment are crucial to improving outcomes and survival rates. Risk factors include age, family history, certain gene mutations, prior history of breast cancer, exposure to estrogen, and lifestyle habits like alcohol consumption and inactivity. Symptoms include changes in the skin on the breast, such as dimpling, lumps or thickening, changes in size or shape, and discharge from the nipple. Diagnosis is often made through a clinical breast exam, mammogram, biopsy, and possibly additional imaging tests. Treatment options include surgery, chemotherapy, radiation therapy, hormone therapy, and targeted therapy. The choice of treatment method depends on the stage and characteristics of cancer.AbstractBreast cancer is considered the solid tumor most sensitive to chemotherapy. However, it can become resistant to various chemotherapeutic drugs, including doxorubicin, which triggers cell death by intercalation between DNA bases, free radical formation, and topoisomerase II inhibition. When drug resistance develops, several miRNAs are dysregulated, suggesting that miRNAs may play a significant role in resistance formation. In the current study, we investigated how doxorubicin sensitivity of breast cancer cells is affected by miR-153-3p and its target gene. The MTT method was used to determine the chemo-sensitizing effect of miR-153-3p on doxorubicin in MCF-7 and MDA-MB-231 cell lines. Results of Western blot and dual luciferase confirmed that miR-153-3p targets KIF20A and decreases its expression. Transwell and flow cytometry experiments showed that miR-153-3p and doxorubicin together had higher effects on MCF-7 and MDA-MB-231 cell proliferation, migration, and invasion, as well as increasing apoptosis and arresting cells in the G1 phase. Proteins related to apoptosis and the cell cycle exhibited the same tendency. Intracellular vesicle formation was inhibited and RAB26 was also downregulated by treatment with miR-153-3p alone or in combination with doxorubicin. Doxorubicin’s ability to suppress tumors may be enhanced by miR-153-3p, according to in vivo studies. According to our findings, miR-153-3p has a direct effect on KIF20A and may regulate the formation of intracellular vesicles, which in turn makes breast cancer cells more susceptible to doxorubicin.Keywords:miR-153-3p;chemosensitivity;breast cancer;doxorubicin;KIF20A
研究领域:
肿瘤学
·
分子生物学
·
癌症研究
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DOI
PubMed
高影响因子
npj Vaccines
·
2025
·Vol. 10
·期 1
·1-13
·
IF 6.5
Zhao Xingyang,Xuan Feichao,Li Zirong,Yin Xiangyi,Zeng Xiaojun,Chen Jiali,Fang Chihua
Hepatocellular carcinoma (HCC) is a highly prevalent malignancy with limited treatment efficacy despite advances in immune checkpoint blockade (ICB) therapy. The inherently weak immune responses in HCC necessitate novel strategies to improve anti-tumor immunity and synergize with ICB therapy. Kinesin family member 20A (KIF20A) is a tumor-associated antigen (TAA) overexpressed in HCC, and it could be a promising target for vaccine development. This study confirmed KIF20A as a promising immunogenic antigen through transcriptomic mRNA sequencing analysis in the context of HCC. Therefore, we developed a thermosensitive hydrogel vaccine formulation (K/R Lip @Gel) to optimize antigen delivery while enabling sustained in vivo release. The vaccine efficiently elicited robust immune responses by activating DCs and T cells. Moreover, K/R Lip @Gel improved the therapeutic efficacy of PD-L1 blockade in subcutaneous and orthotopic cell-derived xenograft (CDX) models, along with immune-humanized patient-derived xenograft (PDX) HCC models, which was evidenced by improved maturation of DCs and elevated infiltration and activation of CD8 + T cells. These findings highlight the potential of KIF20A-based vaccines to synergistically improve ICB therapy outcomes in HCC, providing a promising approach for enhancing anti-tumor immunity and improving clinical outcomes.
研究领域:
肿瘤学
·
免疫学
·
分子生物学
·
癌症治疗
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DOI
PubMed
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Cell Death & Disease
·
2026
·Vol. 17
·期 1
·218
·
IF 12.2
Zhang Ziyun,Li Yi,Hu Jingjiang,Tang Xingjie,Li Zhanpeng,Sun Xiaoyan,Feng Dade,Yao Yixin,Mao Chao,Tao Yongguang,Xie Li,Luo Huaiqing,Li Yufei,Yu Xing,Peng Xiaoning,Cong Li,Jiang Yiqun
Oral squamous cell carcinoma (OSCC) is an aggressive malignancy characterized by poor prognosis, largely attributable to cancer stem cell (CSC) persistence and ferroptosis resistance. However, the molecular mechanisms that coordinately regulate stemness maintenance and ferroptosis suppression in OSCC remain insufficiently characterized. In this study, KIF20A was identified as significantly overexpressed in OSCC and strongly correlated with adverse clinical outcomes. An integrative approach identified DHX9 as a candidate interactor of KIF20A. Mechanistic investigations revealed that KIF20A regulates DHX9 nucleocytoplasmic distribution and inhibits TRIM21-mediated K48-linked polyubiquitination at DHX9-K755, thereby preventing its proteasomal degradation and enhancing protein stability. Elevated DHX9 enhanced SOX2 mRNA stability, leading to upregulation of SOX2, a central regulator of both CSC maintenance and ferroptosis resistance. Functionally, KIF20A promoted CSC phenotypes, inhibited ferroptosis in vitro and in vivo, and activated the PI3K/AKT signaling pathway. Notably, treatment with ENMD-2076 (identified through Connectivity Map analysis) significantly reduced KIF20A expression, attenuated CSC characteristics, augmented cisplatin sensitivity, and exerted marked antitumor activity. These findings elucidate a novel KIF20A-DHX9-SOX2 regulatory axis that simultaneously governs CSC maintenance and ferroptosis evasion in OSCC. Targeting KIF20A, either as a monotherapy or in combination with chemotherapy, may offer a promising strategy to improve therapeutic outcomes in OSCC.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2026
·
IF 8.7
Huanhuan Hu,Pengbo Wang,Zhihong Kong,Yibo Yang,Siyun Liu,Guanjie Li,Chuhan Wang,Jiaqi Jiang,Qifang He,Xiangxiang Cao,Qiaohui Zhao,Huigen Feng,Guojie Ji
Gastric adenocarcinoma is a major clinical challenge due to its aggressive progression and immunosuppressive microenvironment. Here, we identify KIF20A, a mitotic kinesin, is identified as a central oncogenic driver that promotes tumor cell proliferation, migration, and immune evasion. Through integrated bulk and single-cell transcriptomic analyses of gastric adenocarcinoma tissues ( n = 13 patients), we demonstrate that KIF20A overexpression was shown to correlate with poor prognosis ( P < 0.001) and drives cell cycle dysregulation via CDC45/ORC1-mediated G2/M checkpoint bypass. Mechanistically, KIF20A+ epithelial cells exhibited enriched activation of RUNX2-dependent migratory programs (AUCell score: 0.23 vs. 0.15 in KIF20A− cells, P < 0.001) and suppressed intrinsic apoptosis through BCL2 upregulation. Single-cell trajectory analysis revealed that KIF20A+ cells orchestrate macrophage M2 polarization via SPP1-CD44 signaling, fostering an immunosuppressive niche. Pharmacologically, the multi-kinase inhibitor Sorafenib suppresses KIF20A expression (IC₅₀ = 10 μM) and induced mitochondrial dysfunction, as evidenced by glutathione depletion (ΔGSH = −59%, P < 0.01) and ROS accumulation (ΔMDA = +45%, P < 0.001). Functional assays confirmed sorafenib's dose-dependent inhibition of proliferation (CCK-8: 38.5% reduction at 10 μM) and migration (Transwell: 70% suppression at 10 μM), mediated through G2/M arrest (flow cytometry: G2/M population Δ = +10.6%, P < 0.01). Molecular docking identified a high-affinity interaction between sorafenib and KIF20A (binding energy: −6.11 kcal/mol), suggesting direct targeting. The current study unveiled KIF20A as a dual regulator of tumor-intrinsic malignancy and immune evasion, positioning sorafenib as a promising therapeutic agent to disrupt KIF20A-driven pathways in gastric adenocarcinoma.
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