{"title":"EphrinA2 promotes glioma cell migration and invasion through EphA2 and FAK.","authors":"Nozomi Hirai, Sho Tamai, Toshiya Ichinose, Hemragul Sabit, Norihiko Saito, Satoshi Iwabuchi, Mitsutoshi Nakada","doi":"10.1186/s12935-025-03826-7","DOIUrl":"10.1186/s12935-025-03826-7","url":null,"abstract":"<p><strong>Background: </strong>EphrinA2, a ligand of the Eph receptor tyrosine kinase family, is implicated in the malignant phenotypes of various cancer cells. However, its function in glioblastoma remains unclear. Therefore, this study aimed to investigate the function and molecular mechanisms of ephrinA2 in the glioblastoma cells.</p><p><strong>Methods: </strong>EphrinA2 expression in five glioma cell lines and 40 cases of glioblastoma tissue obtained at surgery was examined. Additionally, we examined the effects of ephrinA2 knockdown in the migration and invasion of glioma cells in vitro and in vivo. Moreover, western blotting was performed to elucidate the mechanisms of ephrinA2 in glioma cell invasion and migration.</p><p><strong>Results: </strong>QRT-PCR showed that ephrinA2 was highly expressed in T98G and SNB19 cells. EphrinA2 knockdown shortened cell protrusions and reduced the migration and invasion abilities of T98G and SNB19 cells, which was confirmed by time-lapse dynamic observations. Western blotting showed that ephrinA2 knockdown suppressed phosphorylation of FAK at Tyr861 and EphA2 at Ser897 in glioma cells. Moreover, immunohistochemical analysis of glioblastoma samples showed that glioma cell invasion into normal brain was significantly higher in the ephrinA2 high expression group than in the low expression group.</p><p><strong>Conclusion: </strong>EphrinA2 may be involved in promoting glioblastoma invasion by regulating FAK and EphA2 phosphorylation.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"191"},"PeriodicalIF":5.3,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12102856/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Targeting PIK3CB/YAP1 improves the sensitivity of paclitaxel by suppressing aging in head and neck squamous tumor cells.","authors":"Junzhi Liu, Huimin Li, Ruotong Sun, Guoguang Ying, Zheng Liang","doi":"10.1186/s12935-025-03818-7","DOIUrl":"10.1186/s12935-025-03818-7","url":null,"abstract":"<p><strong>Background: </strong>Tumor cell senescence reduces sensitivity to anticancer drugs, making senescent cell elimination an ideal strategy to enhance chemotherapy sensitivity. The interaction between the PI3K/Akt and Hippo/YAP1 pathways is increasingly studied, but the role of PIK3CB, YAP1, and their impact on senescence and chemotherapy sensitivity in head and neck tumors is unclear.</p><p><strong>Methods: </strong>Public datasets (GEO, TCGA, HPA) were analyzed for PIK3CB expression and clinical associations. Immunohistochemistry, cell proliferation assays, DNA replication, colony formation, aging markers, and DNA damage assessments were conducted. Bulk and single-cell transcriptomics and proteomics data were analyzed. Cell passage effects on aging and the impact of PIK3CB modulation on YAP1 were evaluated. Potential drugs targeting PIK3CB were identified, and the effects of senescent cell clearance drugs on clonogenic abilities and chemotherapy sensitivity were assessed.</p><p><strong>Results: </strong>Elevated PIK3CB expression in HNSCC tumors correlated with advanced stages, older age, and decreased survival. PIK3CB and YAP1 expressions were strongly correlated, impacting aging pathways and cellular proliferation. Modulation of PIK3CB affected tumor cell proliferation, aging, and DNA damage. The combined application of navitoclax and paclitaxel can reduce tumor cell proliferation and autonomous migration ability, influenced by the levels of PIK3CB.</p><p><strong>Conclusion: </strong>High PIK3CB expression in head and neck cancers is linked to poor prognosis and advanced tumor grades. PIK3CB promotes cell proliferation and reduces aging via the YAP1 pathway. The combination of navitoclax and paclitaxel reduces tumor cell proliferation and autonomous migration ability, providing a basis for further exploration of increasing chemotherapy sensitivity.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"190"},"PeriodicalIF":5.3,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12102897/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"UFUR maintenance therapy significantly improves survival in locally advanced head and neck squamous cell carcinoma following definitive chemoradiotherapy.","authors":"Jason Chia-Hsun Hsieh, Ming-Yu Lien, Pei-Hung Chang, Hung-Ming Wang, Kun-Yun Yeh, Ching-Liang Ho, Ching-Yun Hsieh, Meng-Che Hsieh, Jia-Hong Chen","doi":"10.1186/s12935-025-03807-w","DOIUrl":"10.1186/s12935-025-03807-w","url":null,"abstract":"<p><strong>Background: </strong>Head and neck squamous cell carcinoma (HNSCC) presents significant therapeutic challenges, particularly in patients with advanced disease. Despite advancements in treatment, high recurrence rates and poor overall survival (OS) remain major concerns. This study evaluates the impact of tegafur-uracil (UFUR) maintenance therapy on survival outcomes in patients with advanced HNSCC following definitive chemoradiotherapy.</p><p><strong>Methods: </strong>A cohort of 424 advanced HNSCC patients treated with definitive chemoradiotherapy were analyzed, with a median follow-up of 25 months. Patients were stratified into UFUR (+) and UFUR (-) groups, with baseline characteristics balanced across both arms. Oncologic outcomes, including recurrence-free survival (RFS), OS, locoregional recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were compared between these groups.</p><p><strong>Results: </strong>UFUR maintenance therapy significantly reduced recurrence rates (34% vs. 47%, p < 0.002), driven primarily by improving locoregional control (23% vs. 37%, p < 0.001). While distant metastasis rates were similar between groups, UFUR (+) patients demonstrated a markedly improved median OS (51.6 months vs. 24.3 months, p < 0.001). The UFUR (+) group also showed superior median LRFS (36.9 months vs. 20.2 months, p = 0.003) and DMFS (44.0 months vs. 23.5 months, p = 0.010). Subgroup analysis confirmed the benefits of UFUR maintenance across different stages of disease. Multivariate analysis identified UFUR maintenance, gender, and T stage as independent predictors of survival.</p><p><strong>Conclusion: </strong>UFUR maintenance therapy significantly improves survival outcomes in patients with advanced HNSCC following definitive chemoradiotherapy, particularly through enhanced locoregional control, and should be considered a key component of personalized treatment strategies.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"187"},"PeriodicalIF":5.3,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12102819/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"NCAPD3 contributes to lung cancer progression through modulated lactate-induced histone lactylation and MEK/ERK/LDHA axis.","authors":"Zhibo Chang","doi":"10.1186/s12935-025-03814-x","DOIUrl":"10.1186/s12935-025-03814-x","url":null,"abstract":"<p><p>Lung cancer (LC) is one of the most common malignant tumors globally. Non-SMC condensin II complex subunit D3 (NCAPD3) has been involved in the progression of many kinds of tumors. However, the effects of NCAPD3 in LC remain unclear. NCAPD3 expression was investigated by the Ualcan database and using Western blot. The effect of NCAPD3 on prognosis was explored via the Kaplan-Meier plotter database. Cell viability, colony formation, apoptosis, and Transwell assays, and in vivo tumorigenesis were performed to reveal the biological roles of NCAPD3. Glycolysis was assessed via measurement of glucose consumption, extracellular acidification rate (ECAR), lactate production, and ATP levels. The deeper mechanisms of NCAPD3 were investigated by Western blot and rescue experiments. Upregulation of NCAPD3 levels in LC tissues was found in Ualcan and significantly associated with poor prognosis. The expression of NCAPD3 was up-regulated in LC cell lines compared to BEAS-2B cells. Knockdown and overexpression experiments suggested that proliferation, apoptosis, migration, invasion, and glycolysis were regulated by NCAPD3 via the MEK/ERK/LDHA pathway. Additionally, NCAPD3 knockdown inhibited tumor growth in vivo. Mechanistically, NCAPD3 overexpression-mediated activation of the MEK/ERK/LDHA pathway and proliferation, Glucose uptake, and glycolysis were attenuated by MEK inhibitor U0126. Also, histone lactylation helps in tumorigenesis by promoting NCAPD3 expression. Taken together, our results revealed that histone lactylation of NCAPD3 promoted proliferation, migration, invasion, and glycolysis through modulating the MEK/ERK/LDHA signaling pathway in LC, which highlights a novel understanding of NCAPD3 in LC.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"189"},"PeriodicalIF":5.3,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12102810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Emerging roles of non-coding RNA derived from extracellular vesicles in regulating PD-1/PD-L1 pathway: insights into cancer immunotherapy and clinical applications.","authors":"Haixia Zhang, Lianfeng Gong, Li Yu, Chenge Xian, Zhaowu Ma, Xianwang Wang, Ruohan Xia","doi":"10.1186/s12935-025-03809-8","DOIUrl":"10.1186/s12935-025-03809-8","url":null,"abstract":"<p><p>Numerous studies have demonstrated that extracellular vesicles (EVs) carry a variety of noncoding RNAs (ncRNAs), which can be taken up by neighboring cells or transported to distant sites via bodily fluids, thereby facilitating intercellular communication and regulating multiple cellular functions. Within the tumor microenvironment, EV-ncRNA, on the one hand, regulate the expression of PD-L1, thereby influencing tumor immune evasion, promoting tumor cell proliferation, and enhancing tumor growth, invasion, and metastasis in vivo. On the other hand, these specific EV-ncRNAs can also modulate the functions of immune cells (such as CD8 + T cells, macrophages, and NK cells) through various molecular mechanisms, inducing an immunosuppressive microenvironment and promoting resistance to anti-PD-1 therapy. Therefore, delving into the molecular mechanisms underlying EV-ncRNA regulation of immune checkpoints presents compelling therapeutic prospects for strategies that selectively target EV-ncRNAs. In this review, we elaborate on the cutting-edge research progress related to EV-ncRNAs in the context of cancer and dissect their pivotal roles in the PD-1/PD-L1 immune checkpoint pathway. We also highlight the promising clinical applications of EV-ncRNAs in anti-PD-1/PD-L1 immunotherapy, bridging basic research with practical clinical applications.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"188"},"PeriodicalIF":5.3,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12103061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sina Shaernejad, Ali Nosrat, Maryam Baeeri, Nasser Hashemi Goradel, Mirsalim SeyedSadeghi, Mostafa Akbariani, AmirAhmad Arabzadeh, Mahban Rahimifard, Hamed Haghi-Aminjan
{"title":"Role of hesperidin/hesperetin against chemotherapy-induced cardiotoxicity: a systematic review of non-clinical studies.","authors":"Sina Shaernejad, Ali Nosrat, Maryam Baeeri, Nasser Hashemi Goradel, Mirsalim SeyedSadeghi, Mostafa Akbariani, AmirAhmad Arabzadeh, Mahban Rahimifard, Hamed Haghi-Aminjan","doi":"10.1186/s12935-025-03828-5","DOIUrl":"10.1186/s12935-025-03828-5","url":null,"abstract":"<p><p>Despite the undeniable role of chemotherapeutics in cancer treatment, their administration may be associated with various side effects. Cardiac injury is among the most crucial side effects related to the induction of chemotherapeutic agents. Since the heart is a vital organ, cardiotoxicity often prevents clinicians from continuing chemotherapy. Hesperidin and hesperetin, flavonoids derived from citrus fruits, possess several pharmaceutical properties. This study firstly explores the cardioprotective effects of hesperidin and hesperetin against chemotherapy-induced cardiotoxicity mechanisms, emphasizing their potential as adjunctive therapies. Key literature gaps are identified, and further mechanistic studies will be proposed. The findings underscore the translational potential of these flavonoids, advocating for rigorous preclinical optimization and clinical trials to validate their efficacy and safety. This review lays a foundation for integrating natural compounds into cardioprotective strategies in oncology. A systematic search was conducted in databases (PubMed, Scopus, ISI) until May 2025, according to PRISMA principles. The search terms were chosen according to our research objective and queried in the title and abstract. Following the screening of 82 papers, twelve articles were selected based on our inclusion and exclusion criteria. Based on the evaluated results, chemotherapy adversely affects cardiac tissue, leading to elevated risks of morbidity and mortality. Co-administration of hesperidin and hesperetin with chemotherapy prevents heart injury and preserves cardiac function, maintaining it almost like a normal heart. The protective role of hesperidin and hesperetin is based on their ability to fight free radicals, reduce inflammation, and stop cell death. Nonclinical investigations indicate that hesperidin and hesperetin ameliorate chemotherapy-induced cardiotoxicity. Nonetheless, they may influence the efficacy of anticancer medications, which primarily function by elevating oxidants, inflammation, and apoptosis. This indicates that meticulously designed trials are necessary to evaluate the efficacy and safety of this combination along with the synergistic potential of them in preventing chemotherapy-induced cardiotoxicity while maintaining anticancer effectiveness.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"186"},"PeriodicalIF":5.3,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12100833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hye Joung Cho, Jihwan Yoo, Ran Joo Choi, Jae-Seon Lee, Ryong Nam Kim, Junseong Park, Ju Hyung Moon, Eui Hyun Kim, Wan-Yee Teo, Jong Hee Chang, Soo-Youl Kim, Seok-Gu Kang
{"title":"N-phenylmaleimide induces bioenergetic switch and suppresses tumor growth in glioblastoma tumorspheres by inhibiting SLC25A11.","authors":"Hye Joung Cho, Jihwan Yoo, Ran Joo Choi, Jae-Seon Lee, Ryong Nam Kim, Junseong Park, Ju Hyung Moon, Eui Hyun Kim, Wan-Yee Teo, Jong Hee Chang, Soo-Youl Kim, Seok-Gu Kang","doi":"10.1186/s12935-025-03813-y","DOIUrl":"10.1186/s12935-025-03813-y","url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma (GBM) is a highly resistant tumor, and targeting its bioenergetics could be a potential treatment strategy. GBM cells depend on cytosolic nicotinamide adenine dinucleotide (NADH), which is transported into the mitochondria via the malate-aspartate shuttle (MAS) for ATP production. N-phenylmaleimide (KN612) is a MAS inhibitor that targets SLC25A11, an antiporter protein of the MAS. Therefore, this study investigated the effects of KN612 in GBM treatment using in vitro and in vivo models.</p><p><strong>Methods: </strong>We examined the biological effects of KN612 in GBM tumorspheres (TSs), including its effects on cell viability, ATP level, cell cycle, stemness, invasive properties, energy metabolic pathways, and transcriptomes. Additionally, we investigated the in vivo efficacy of KN612 in a mouse orthotopic xenograft model.</p><p><strong>Results: </strong>Transcriptomic analysis showed that SLC25A11 mRNA expression was significantly higher in GBM TSs than in normal human astrocytes. Additionally, siRNA-mediated SLC25A11 knockdown and KN612-mediated MAS inhibition decreased the oxygen consumption rate, ATP levels, mitochondrial activity, and cell viability in GBM TSs and decreased the stemness and invasion ability of GBM cells. Moreover, gene ontology functional annotation indicated that KN612 treatment inhibited cell-cycle and mitotic processes. Furthermore, KN612 treatment reduced tumor size and prolonged survival in an orthotopic xenograft model.</p><p><strong>Conclusions: </strong>Targeting GBM bioenergetics using KN612 may represent a novel and effective approach for GBM treatment.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"184"},"PeriodicalIF":5.3,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12096590/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"FAM111B and FANCD2, a dual expression signature, defines a distinct phenotype of pancreatic cancer.","authors":"Fang Wei, Wanying Li, Ting Zhou, Lijuan Feng, Xianglin Yuan, Lihong Zhang","doi":"10.1186/s12935-025-03819-6","DOIUrl":"10.1186/s12935-025-03819-6","url":null,"abstract":"<p><strong>Background: </strong>Despite various treatment strategies, the incidence and mortality of pancreatic cancer (PC) are among the highest for malignant tumors. Furthermore, there is a lack of effective molecular typing and targeted therapy to treat PC subtypes.</p><p><strong>Methods: </strong>Multiplex immunofluorescence experiments were performed to explore the roles of FAM111B, FANCD2, KRAS and TP53 in human PC tissues. Kaplan-Meier survival curves were generated and a nomogram was prepared for prognostic prediction. Protein correlations were analyzed using human PC tissues and TCGA and GEO data. Pathways analysis, immunoanalysis, and drug susceptibility analysis were performed based on information in the TCGA database.</p><p><strong>Results: </strong>Our results indicate that expression of FAM111B and FANCD2 is correlated in human PC tissues and comprises a dual expression signature with predictive value for the prognosis of PC. Using information in public databases, we confirmed the oncogenic relevance of FAM111B and FANCD2 in PC and identified a positive correlation between FAM111B, FANCD2, TP53 and KRAS.FAM111B and FANCD2 jointly regulate ferroptosis, mitotic nuclear division, and nuclear division pathways. Both proteins were demonstrated to be positively correlated with markers of CD4 + Th2 cells and PD-L1 in the tumor microenvironment. Furthermore, drug sensitivity analysis suggested that patients with high FAM111B or FANCD2 expression were highly sensitive to chemotherapeutic and targeted drugs, indicating that these proteins may serve as predictors of treatment efficacy.</p><p><strong>Conclusion: </strong>Elevated dual expression of FAM111B and FANCD2 is indicative of poor prognosis, alters the immune microenvironment, and exhibits sensitivity to certain therapeutic agents. Consequently, the high FAM111B/FANCD2 expression subtype may represent a novel and distinct phenotype of PC.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"185"},"PeriodicalIF":5.3,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12101032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"CCDC110 promotes the progression of hepatocellular carcinoma by activating the TGF-β/SMAD signaling pathway through targeted regulation of TGFBR1.","authors":"Hao Shen, Haifeng Li, Haodong Tang","doi":"10.1186/s12935-025-03803-0","DOIUrl":"10.1186/s12935-025-03803-0","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) is recognized for its high growth rate, high degree of invasiveness, and tendency to spread, leading to a significant number of deaths. In the course of studying the transcriptome of HCC tissues, the protein coiled-coil domain-containing 110 (CCDC110) was identified. By employing tandem mass tag (TMT) quantitative proteomics, this research identified transforming growth factor beta receptor 1 (TGFBR1) as a potential target influenced by CCDC110. The purpose of this study was to examine the role of CCDC110 in the growth and invasion of HCC and to identify new potential targets for the treatment of HCC.</p><p><strong>Methods: </strong>In vitro and in vivo experiments were conducted to investigate the role and mechanism of CCDC110 in promoting the malignant behaviors of hepatocellular carcinoma through the regulation of TGFBR1.</p><p><strong>Results: </strong>We determined that the mRNA and protein levels of CCDC110 are elevated in hepatocellular carcinoma tissues and cell lines, which is correlated with a worse patient prognosis. CCDC110 enhances the proliferation of hepatocellular carcinoma cells, reduces their apoptosis, and increases their migration and invasion capabilities. In the cytoplasm, CCDC110 interacts with TGFBR1, enhancing stability of TGFBR1, promoting proliferation, and reducing the apoptosis, migration, and invasion of hepatocellular carcinoma cells through TGFBR1 both in vivo and in vitro. The CCDC110-TGFBR1 axis stimulates EMT, thereby enhancing the malignant biological behavior of hepatocellular carcinoma by activating the TGF-β/SMAD signaling pathway. The protein levels of CCDC110/TGFBR1 in hepatocellular carcinoma tissues are highly expressed and positively correlated. A combined analysis of CCDC110 and TGFBR1 provides improved guidance for the prognosis of patients with hepatocellular carcinoma.</p><p><strong>Conclusion: </strong>CCDC110 is highly expressed in hepatocellular carcinoma tissues and cell lines, and the CCDC110-TGFBR1 axis facilitates EMT and the malignant biological behavior of hepatocellular carcinoma through the activation of the TGF-β/SMAD signaling pathway.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"183"},"PeriodicalIF":5.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12093845/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The regulation of LRPs by miRNAs in cancer: influencing cancer characteristics and responses to treatment.","authors":"Lianyue Qu, Fan Wang, Yuxiang Wang, Zixuan Li","doi":"10.1186/s12935-025-03804-z","DOIUrl":"10.1186/s12935-025-03804-z","url":null,"abstract":"<p><p>The low-density lipoprotein receptor-related protein (LRP) family is a group of cell surface receptors that participate in a variety of biological processes, including lipid metabolism, Wnt signaling, and bone metabolism. miRNAs are small non-coding RNA molecules that regulate gene expression and play a role in many biological processes, including the occurrence and development of tumors. Accumulating evidence demonstrates that LRP members are modulated by miRNAs across multiple cancer types, influencing key oncogenic processes-including tumor cell proliferation, apoptosis suppression, extracellular matrix remodeling, cell adhesion, and angiogenesis. The LRPs, miRNAs, their upstream lncRNAs, and downstream signaling molecules often form complex signaling pathways to regulate the activity of tumor cells. However, the tissue-specific roles and mechanistic underpinnings of these pathways remain incompletely understood. When examining the emerging concept of the interaction between miRNAs and LRPs, we emphasize the significance of these complex regulatory layers in the initiation and progression of cancer. Collectively, these findings are critical for advancing our understanding of the role of the LRPs family in the occurrence and development of tumors, as well as for the development of new strategies for cancer treatment.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"182"},"PeriodicalIF":5.3,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12085831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}