Cancer Biology & Therapy最新文献

Fractionated radiotherapy initiated at the early stage of bone metastasis is effective to prolong survival in mouse model. 骨转移早期分次放疗可有效延长小鼠生存期。

IF 4.4 4区医学

Cancer Biology & Therapy Pub Date : 2025-12-01 Epub Date: 2025-01-20 DOI: 10.1080/15384047.2025.2455756

Yun Zhang, Zhunyi Gao, Ziwei Qi, Jiahe Xu, Jiao Xue, Lujie Xiong, Junhui Wang, Yuhui Huang, Songbing Qin

{"title":"Fractionated radiotherapy initiated at the early stage of bone metastasis is effective to prolong survival in mouse model.","authors":"Yun Zhang, Zhunyi Gao, Ziwei Qi, Jiahe Xu, Jiao Xue, Lujie Xiong, Junhui Wang, Yuhui Huang, Songbing Qin","doi":"10.1080/15384047.2025.2455756","DOIUrl":"https://doi.org/10.1080/15384047.2025.2455756","url":null,"abstract":"Background and purpose: Bone metastasis is common for breast cancer and associated with poor prognosis. Currently, radiotherapy (RT) serves as the standard treatment for patients exhibiting symptoms of bone metastasis to alleviate pain. Whether earlier application of RT will better control bone metastasis remains unclear.Methods: We utilized a mouse model of breast cancer bone metastasis by intra-femoral injection of 4T1-luc breast tumor cells. The bone metastasis was treated by RT using various doses, timings, and modalities. Tumor growth was assessed through bioluminescence imaging, and lung metastases was quantified following lung tissue fixation. Flow cytometry was employed to analyze alterations in immune cell populations.Results: Single high-dose RT suppressed tumor growth of bone metastases, but caused severe side effects. Conversely, fractionated RT mitigated tumor growth in bone metastases with fewer adverse effects. Fractioned RT initiated at the early stage of bone metastasis effectively inhibited tumor growth in the bone, suppressed secondary lung metastases, and prolonged mouse survival. In line with the known pro- and anti-metastatic effects of neutrophils and T cells in breast cancer, respectively, earlier fractioned RT consistently decreased the proportions of neutrophils while increased the proportions of T cells in both the bone and the lung tissues.Conclusion: The data suggest that fractionated RT can inhibit the progression of early stage of bone metastasis and reduce secondary lung metastasis, leading to favorable outcomes. Therefore, these findings provide preclinical evidence to support the application of fractionated RT to treat patients with bone metastasis as earlier as possible.","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"26 1","pages":"2455756"},"PeriodicalIF":4.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Daurisoline inhibits glycolysis of lung cancer by targeting the AKT-HK2 axis. Daurisoline通过靶向AKT-HK2轴抑制肺癌糖酵解。

IF 4.4 4区医学

Cancer Biology & Therapy Pub Date : 2025-12-01 Epub Date: 2024-12-19 DOI: 10.1080/15384047.2024.2442556

Shi-Ming Tan, Lan Luo, Yi-Fu He, Wei Li, Xin-Xing Wan

引用次数: 0

Long-term effects of neoadjuvant chemotherapy in variant histology locally advanced colon cancer: a propensity score-matched analysis. 新辅助化疗对不同组织学局部晚期结肠癌的长期影响：倾向评分匹配分析。

IF 4.4 4区医学

Cancer Biology & Therapy Pub Date : 2025-12-01 Epub Date: 2024-12-24 DOI: 10.1080/15384047.2024.2441511

Qiancheng Wang, Shiyang Jin, Zeshen Wang, Yuming Ju, Kuan Wang

{"title":"Long-term effects of neoadjuvant chemotherapy in variant histology locally advanced colon cancer: a propensity score-matched analysis.","authors":"Qiancheng Wang, Shiyang Jin, Zeshen Wang, Yuming Ju, Kuan Wang","doi":"10.1080/15384047.2024.2441511","DOIUrl":"https://doi.org/10.1080/15384047.2024.2441511","url":null,"abstract":"Purpose: Neoadjuvant chemotherapy (NAC) has proven valuable in treating locally advanced colon cancer (LACC) and is included as a treatment option for patients with clinical T4b colon cancer by the National Comprehensive Cancer Network. However, the long-term survival benefit of NAC in LACC remains debated, due to a lack of conclusive clinical trial results identifying the patients who would benefit most from NAC. This study aimed to assess the efficacy of NAC in patients with LACC based on histological subtype.Patients and methods: This retrospective study analyzed 3,709 patients with LACC who underwent curative resection at Harbin Medical University Cancer Hospital between 2014 and 2018. Patients were grouped into two groups: neoadjuvant chemotherapy (NAC) and adjuvant chemotherapy (AC) groups. Propensity score matching (PSM) was used to adjust for confounders, and survival outcomes of the two groups across different histological subtypes were evaluated using Kaplan-Meier (K-M) curves and log-rank tests.Results: Patients with non-mucinous adenocarcinoma (NMAC) treated with NAC had a significantly improved 5-year OS rate (76.3% vs. 69.2%, p = .039) and DFS rate (67.2% vs. 60.1%, p = .041) compared with patients treated with AC. However, there was no significant difference in OS and DFS between the two treatment groups among patients with mucinous adenocarcinoma (MAC) and signet ring cell carcinoma (SRCC).Conclusion: In patients with LACC, the prognostic value of NAC varied by histology. NMAC may serve as a predictor of improved long-term survival benefit from NAC in these patients.","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"26 1","pages":"2441511"},"PeriodicalIF":4.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sigma1 inhibitor suppression of adaptive immune resistance mechanisms mediated by cancer cell derived extracellular vesicles. Sigma1 抑制剂抑制由癌细胞衍生的细胞外囊泡介导的适应性免疫抵抗机制。

IF 4.4 4区医学

Cancer Biology & Therapy Pub Date : 2025-12-01 Epub Date: 2025-01-26 DOI: 10.1080/15384047.2025.2455722

Paola A Castagnino, Derick A Haas, Luca Musante, Nathalia A Tancler, Bach V Tran, Rhonda Kean, Alexandra R Steck, Luis A Martinez, Elahe A Mostaghel, D Craig Hooper, Felix J Kim

{"title":"Sigma1 inhibitor suppression of adaptive immune resistance mechanisms mediated by cancer cell derived extracellular vesicles.","authors":"Paola A Castagnino, Derick A Haas, Luca Musante, Nathalia A Tancler, Bach V Tran, Rhonda Kean, Alexandra R Steck, Luis A Martinez, Elahe A Mostaghel, D Craig Hooper, Felix J Kim","doi":"10.1080/15384047.2025.2455722","DOIUrl":"10.1080/15384047.2025.2455722","url":null,"abstract":"Adaptive immune resistance in cancer describes the various mechanisms by which tumors adapt to evade anti-tumor immune responses. IFN-γ induction of programmed death-ligand 1 (PD-L1) was the first defined and validated adaptive immune resistance mechanism. The endoplasmic reticulum (ER) is central to adaptive immune resistance as immune modulatory secreted and integral membrane proteins are dependent on ER. Sigma1 is a unique ligand-regulated integral membrane scaffolding protein enriched in the ER of cancer cells. PD-L1 is an integral membrane glycoprotein that is translated into the ER and processed through the cellular secretory pathway. At the cell surface, PD-L1 is an immune checkpoint molecule that binds PD-1 on activated T-cells and blocks anti-tumor immunity. PD-L1 can also be incorporated into cancer cell-derived extracellular vesicles (EVs), and EV-associated PD-L1 can inactivate T-cells within the tumor microenvironment. Here, we demonstrate that a selective small molecule inhibitor of Sigma1 can block IFN-γ mediated adaptive immune resistance in part by altering the incorporation of PD-L1 into cancer cell-derived EVs. Sigma1 inhibition blocked post-translational maturation of PD-L1 downstream of IFN-γ/STAT1 signaling. Subsequently, EVs released in response to IFN-γ stimulation were significantly less potent suppressors of T-cell activation. These results suggest that by reducing tumor derived immune suppressive EVs, Sigma1 inhibition may promote antitumor immunity. Sigma1 modulation presents a novel approach to regulating the tumor immune microenvironment by altering the content and production of EVs. Altogether, these data support the notion that Sigma1 may play a role in adaptive immune resistance in the tumor microenvironment.","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"26 1","pages":"2455722"},"PeriodicalIF":4.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11776462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143037220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effect of extracellular vesicle ZNF280B derived from lung cancer stem cells on lung cancer progression. 肺癌干细胞来源的细胞外囊泡ZNF280B对肺癌进展的影响

IF 4.4 4区医学

Cancer Biology & Therapy Pub Date : 2025-12-01 Epub Date: 2025-01-17 DOI: 10.1080/15384047.2025.2450849

Qixia Guo, Jiayan Lu, Hui Zhao, Ding Zhou, Hua Liu

{"title":"Effect of extracellular vesicle ZNF280B derived from lung cancer stem cells on lung cancer progression.","authors":"Qixia Guo, Jiayan Lu, Hui Zhao, Ding Zhou, Hua Liu","doi":"10.1080/15384047.2025.2450849","DOIUrl":"https://doi.org/10.1080/15384047.2025.2450849","url":null,"abstract":"Objective: The purpose of this research was to investigate the role of extracellular vesicles derived from lung cancer stem cells (lung CSCs-EVs) in lung cancer and to explore their potential mechanisms.Methods: Lung CSCs were first isolated and verified using flow cytometry and RT-qPCR assays. Lung CSCs-EVs were extracted through ultracentrifugation and further characterized using transmission electron microscopy and Western blotting. The interaction between lung CSCs-EVs and lung cancer cells was observed through PKH67 staining. Subsequently, we analyzed the differentially expressed genes in lung CSCs using bioinformatics data analysis and evaluated the prognostic value of ZNF280B in lung cancer with the Kaplan-Meier Plotter. RT-qPCR was utilized to assess the mRNA expression levels of these genes, while Western blotting was used to evaluate the protein expression levels of ZNF280B and P53. Next, CCK-8 and colony formation assays were conducted to assess the effects of lung CSCs-EVs and ZNF280B on cancer cell proliferation, migration (via wound healing assay), and invasion (using transwell assay). Additionally, subcutaneous tumor-bearing experiments in nude mice were performed to evaluate the roles of lung CSCs-EVs in lung cancer progression in vivo.Results: The results indicated that lung CSCs-EVs accelerated the progression of lung cancer. Mechanistically, these lung CSCs-EVs transferred ZNF280B into cancer cells, leading to the inhibition of P53 expression.Conclusions: In summary, the manuscript first describes the molecular mechanism by which lung CSCs-EVs promote pro-cancer functions in lung cancer through the ZNF280B/P53 axis.","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"26 1","pages":"2450849"},"PeriodicalIF":4.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

NVP-2, in combination with Orlistat, represents a promising therapeutic strategy for acute myeloid leukemia. NVP-2联合奥利司他是治疗急性髓系白血病的一种有前景的治疗策略。

IF 4.4 4区医学

Cancer Biology & Therapy Pub Date : 2025-12-01 Epub Date: 2025-01-12 DOI: 10.1080/15384047.2025.2450859

Qing Zhu, Jia Cheng, Yuqing Gao, Zimu Zhang, Jian Pan, Xin Su, Danhong Fei, Linbo Cai, Juanjuan Yu, Yanling Chen, Wanyan Jiao, Di Wu, Xiaolu Li, Peifang Xiao

{"title":"NVP-2, in combination with Orlistat, represents a promising therapeutic strategy for acute myeloid leukemia.","authors":"Qing Zhu, Jia Cheng, Yuqing Gao, Zimu Zhang, Jian Pan, Xin Su, Danhong Fei, Linbo Cai, Juanjuan Yu, Yanling Chen, Wanyan Jiao, Di Wu, Xiaolu Li, Peifang Xiao","doi":"10.1080/15384047.2025.2450859","DOIUrl":"10.1080/15384047.2025.2450859","url":null,"abstract":"Cell cycle dysregulation and the corresponding metabolic reprogramming play significant roles in tumor development and progression. CDK9, a kinase that regulates gene transcription and cell cycle, also induces oncogene transcription and abnormal cell cycle in AML cells. The function of CDK9 for gene regulation in AML cells requires further exploration. In this study, we knocked down the CDK9 to investigate its effects on the growth and survival of AML cells. Through RNA-seq analysis, we identified that in U937 cells CDK9 regulates numerous genes involved in proliferation and apoptosis, including mTOR, SREBF1, and Bcl-2. Furthermore, our results demonstrated that both CDK9 and FASN are crucial for the proliferation and survival of Kasumi-1 and U937 cells. Mechanistically, MCL1, c-Myc, and Akt/mTOR/SREBF1 may be critical factors and pathways in the combined therapy of NVP-2 and Orlistat. In summary, our study revealed that CDK9 and FASN are vital for maintaining AML cell survival and proliferation. Treatment with NVP-2 and Orlistat may be a promising clinical candidate for patients with AML.","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"26 1","pages":"2450859"},"PeriodicalIF":4.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11730633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142969552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A pan-cancer analysis of MARCH8: molecular characteristics, clinical relevance, and immuno-oncology features.

IF 4.4 4区医学

Cancer Biology & Therapy Pub Date : 2025-12-01 Epub Date: 2025-01-29 DOI: 10.1080/15384047.2025.2458773

Zihan Quan, Songqing Fan, Hongmei Zheng, Yue Ning, Yang Yang

{"title":"A pan-cancer analysis of MARCH8: molecular characteristics, clinical relevance, and immuno-oncology features.","authors":"Zihan Quan, Songqing Fan, Hongmei Zheng, Yue Ning, Yang Yang","doi":"10.1080/15384047.2025.2458773","DOIUrl":"10.1080/15384047.2025.2458773","url":null,"abstract":"Membrane-associated RING-CH8 (MARCH8) is a member of the recently discovered MARCH family of ubiquitin ligases. MARCH8 has been shown to participate in immune responses. However, the role of MARCH8 in prognosis and immunology in human cancers remains largely unknown. The expression of MARCH8 protein was detected via immunohistochemistry in non-small cell lung cancer (NSCLC) and non-cancerous lung tissues. The study investigated the role of MARCH8 in tumor immunity through pan-cancer analysis of multiple databases. MARCH8 genetic alternations and expression were explored with the cBioPortal, GTEx, and TCGA databases. We investigated the role of MARCH8 expression in clinical relevance, prognosis, tumor immune microenvironment, immune checkpoint (ICP) with a series of bioinformatics tools and methods, such as TISIDB database, ESTIMATE, and CIBERSORT method. MARCH8 expression showed cancer-specific dysregulation and was associated with the prognosis of patients in various cancers. MARCH8 was related to the tumor microenvironment and participated in tumor immune regulation. Furthermore, low expression of MARCH8 was associated with poor prognosis and might serve as an independent prognostic biomarker for NSCLC patients. The comprehensive pan-cancer analysis revealed the potential of MARCH8 in tumor-targeted therapy, and suggested MARCH8 as a promising prognostic and immunological pan-cancer biomarker.","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"26 1","pages":"2458773"},"PeriodicalIF":4.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11784653/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

RSK4 promotes the metastasis of clear cell renal cell carcinoma by activating RUNX1-mediated angiogenesis. RSK4通过激活runx1介导的血管生成促进透明细胞肾细胞癌的转移。

IF 4.4 4区医学

Cancer Biology & Therapy Pub Date : 2025-12-01 Epub Date: 2025-01-10 DOI: 10.1080/15384047.2025.2452025

Jing Ma, Yanru Yang, Kaijing Wang, Jin Liu, Junyi Feng, Gongcheng Wang, Shuangping Guo, Linni Fan

{"title":"RSK4 promotes the metastasis of clear cell renal cell carcinoma by activating RUNX1-mediated angiogenesis.","authors":"Jing Ma, Yanru Yang, Kaijing Wang, Jin Liu, Junyi Feng, Gongcheng Wang, Shuangping Guo, Linni Fan","doi":"10.1080/15384047.2025.2452025","DOIUrl":"10.1080/15384047.2025.2452025","url":null,"abstract":"Ribosomal S6 protein kinase 4 (RSK4), a member of the serine‒threonine kinase family, plays a vital role in the Ras‒MAPK pathway. This kinase is responsible for managing several cellular activities, including cell growth, proliferation, survival, and mobility. In this study, we observed higher RSK4 protein expression in clear cell renal cell carcinoma (ccRCC) than in normal kidney tissue, and the overexpression of RSK4 might predict poor outcomes for ccRCC patients. Notably, renal cell carcinoma (RCC) is rich in blood vessels; therefore, this study aimed to explore the biological function of RSK4 in ccRCC progression and its specific regulatory mechanism. We analyzed changes in the expression of target genes through transcriptomic and proteomic assessments. We also conducted tube formation assays and VEGF ELISAs to understand the role of RSK4 in angiogenesis. Additionally, we evaluated the regulatory effect of RUNX1 on EPHA2 transcription using a luciferase reporter gene assay and observed that the effect of RUNX1 on activating EPHA2 transcription was negated after the binding site was mutated. Our findings suggested that RSK4 enhanced tube formation by stimulating VEGF secretion. Concurrently, in vivo experiments confirmed that RSK4 expedited RCC metastasis and angiogenesis. This evidence indicates that RSK4 may serve as a new prognostic marker and play a vital role in RCC metastasis.","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"26 1","pages":"2452025"},"PeriodicalIF":4.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11730630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142963826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeting the IKZF1/BCL-2 axis as a novel therapeutic strategy for treating acute T-cell lymphoblastic leukemia.

IF 4.4 4区医学

Cancer Biology & Therapy Pub Date : 2025-12-01 Epub Date: 2025-01-25 DOI: 10.1080/15384047.2025.2457777

Juan Li, Chunmei Ye, Hui Li, Jun Li

{"title":"Targeting the IKZF1/BCL-2 axis as a novel therapeutic strategy for treating acute T-cell lymphoblastic leukemia.","authors":"Juan Li, Chunmei Ye, Hui Li, Jun Li","doi":"10.1080/15384047.2025.2457777","DOIUrl":"10.1080/15384047.2025.2457777","url":null,"abstract":"Objectives: Acute T-cell lymphoblastic leukemia (T-ALL) is a severe hematologic malignancy with limited treatment options and poor long-term survival. This study explores the role of IKZF1 in regulating BCL-2 expression in T-ALL.Methods: CUT&Tag and CUT&Run assays were employed to assess IKZF1 binding to the BCL-2 promoter. IKZF1 overexpression and knockdown experiments were performed in T-ALL cell lines. The effects of CX-4945 and venetoclax, alone and in combination, were evaluated in vitro and in vivo T-ALL models.Results: CUT&Tag sequencing identified IKZF1 binding to the BCL-2 promoter, establishing it as a transcriptional repressor. Functional assays demonstrated that IKZF1 overexpression reduced BCL-2 mRNA levels and increased repressive histone marks at the BCL-2 promoter, while IKZF1 knockdown led to elevated BCL-2 expression. CX-4945, a CK2 inhibitor, could reduced BCL-2 levels in T-ALL cells. Notably, knockdown of IKZF1 partially rescued the CX-4945-induced repression of BCL-2. These results underscore the CK2-IKZF1 signaling axis as a key regulator of BCL-2 expression. In vitro, CX-4945 enhanced the cytotoxicity of venetoclax, with the combination showing significant synergistic effects and increased apoptosis in T-ALL cell lines. In vivo studies with cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) models demonstrated that CX-4945 and venetoclax combined therapy provided superior therapeutic efficacy, reducing tumor burden and prolonging survival compared to single-agent treatments.Conclusions: IKZF1 represses BCL-2 in T-ALL, and targeting the CK2-IKZF1 axis with CX-4945 and venetoclax offers a promising therapeutic strategy, showing enhanced efficacy and potential as a novel treatment approach for T-ALL.","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"26 1","pages":"2457777"},"PeriodicalIF":4.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11776473/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Upregulation of TTYH3 by lncRNA LUCAT1 through interacting with ALYREF facilitates the metastasis in non-small cell lung cancer. lncRNA LUCAT1通过与ALYREF相互作用上调TTYH3，促进了非小细胞肺癌的转移。

IF 4.4 4区医学

Cancer Biology & Therapy Pub Date : 2025-12-01 Epub Date: 2025-02-10 DOI: 10.1080/15384047.2025.2464966

Fang Fang, Mei Zhao, Jinming Meng, Jiaqi He, Chunlei Yang, Changhong Wang, Jiaxiao Wang, Sheng Xie, Xiaowei Jin, Wei Shi

{"title":"Upregulation of TTYH3 by lncRNA LUCAT1 through interacting with ALYREF facilitates the metastasis in non-small cell lung cancer.","authors":"Fang Fang, Mei Zhao, Jinming Meng, Jiaqi He, Chunlei Yang, Changhong Wang, Jiaxiao Wang, Sheng Xie, Xiaowei Jin, Wei Shi","doi":"10.1080/15384047.2025.2464966","DOIUrl":"10.1080/15384047.2025.2464966","url":null,"abstract":"Metastasis is the predominant culprit of cancer-associated mortality in non-small cell lung cancer (NSCLC). Tweety homolog 3 (TTYH3) reportedly functions vitally in the development of diverse cancers, including NSCLC; nevertheless, its role in NSCLC metastasis remains ambiguous. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot were initially employed to detect TTYH3 expression in NSCLC and normal lung epithelial cells. Subsequently, A549 and NCI-H1650 cells were chosen as NSCLC models in vitro and transfected with short hairpin RNAs (sh-TTYH3, sh-LUCAT1, and sh-ALYREF) or overexpression plasmids (oe-ALYREF and oe-TTYH3). Transwell assays were used for migrative and invasive tests. Epithelial mesenchymal transformation (EMT)-related proteins (E-cadherin, N-cadherin, Vimentin, and Snail) were measured by western blot. A mouse lung metastasis model was built to define the function of TTYH3 in NSCLC metastasis, followed by hematoxylin-eosin staining. RNA pull-down, RNA immunoprecipitation, qRT-PCR, western blot, and actinomycin D assays were adopted to determine the relationships among LUCAT1, ALYREF, and TTYH3. TTYH3 was highly expressed in NSCLC cells relative to normal lung cells. Functionally, TTYH3 knockdown restrained NSCLC migration, invasion, EMT, and metastasis. Mechanistic experiments demonstrated that LUCAT1 bound to ALYREF. After LUCAT1 knockdown, TTYH3 expression and mRNA stability were reduced, which was reversed by ALYREF overexpression. Furthermore, ALYREF overexpression counteracted the inhibitory effects of LUCAT1 knockdown on NSCLC cell migration, invasion, and EMT. TTYH3 overexpression eliminated the suppressive functions of ALYREF downregulation in NSCLC progression. LUCAT1 promotes TTYH3 expression via interacting with ALYREF, thereby facilitating NSCLC migration, invasion, and EMT.","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"26 1","pages":"2464966"},"PeriodicalIF":4.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11817527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0