Histology and histopathology, Vol.41, Nº7, (2026)
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- PublicationOpen AccessTargeting of CDK1 and PRMT5 as a potential therapeutic combination for non-small cell lung cancer(2026) Chunwei Xu; Yonghua Min; Youcai Zhu; Xiaofeng Li; Zhanqiang Zhai; Biología Celular e Histología; Universidad de Murcia, Departamento de Biologia Celular e HistiologiaObjectives. The potential treatment option of targeting protein arginine methyltransferase 5 (PRMT5) has been explored, but further investigation is required to assess the efficacy of combination therapy in non small cell lung cancer (NSCLC). In this study, bioinformatics and online databases were utilized to select the combined therapeutic targets. Methods. The potential kinases associated with PRMT5-related genes in NSCLC were analyzed using The Cancer Genome Atlas (TCGA) database and X2K Appyter (Expression2Kinases) database. In vitro evaluations were conducted to assess the synergistic effects between PRMT5 and cyclin-dependent kinase 1 (CDK1) in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) cell lines. Results. In our study, CDK1 was primarily the kinase associated with PRMT5-related genes in NSCLC. We observed a significant upregulation of PRMT5 and CDK1 expression in NSCLC tissues. Methylthio adenosine phosphorylase (MTAP)-null NSCLC cell lines demonstrated sensitivity to monotherapy with PRMT5i. A considerable synergistic effect was observed in MTAP-null cells when combining PRMT5i with CDK1i, resulting in the inhibition of cell growth and migration. Conclusion. Our research provides evidence supporting the synergistic anti-tumor effects of targeting PRMT5 and CDK1 in MTAP-deficient NSCLC.
- PublicationOpen AccessCantharidic acid causes mitochondrial dysfunction via the Nrf2/HO-1/GPX4 pathway to inhibit colorectal cancer progression(2026) Shulin Dai; Dongyun Zhang; Ting Zhang; Xiaoyu Wang; Yin Li; Wei Huang; Mingliao Niu; Yan Wei; Biología Celular e Histología; Universidad de Murcia, Departamento de Biologia Celular e HistiologiaBackground. Cantharidic acid (CA) is a cantharidin analog and has antitumor effects. This study aimed to investigate the antitumor activity of CA against colorectal cancer (CRC) and the underlying mechanisms of this activity. Methods. The impact of CA on the viability of the normal FHC cell line was evaluated by the CCK-8 assay. The malignant behavior of CRC cells was determined using the CCK-8 assay, colony formation assay, Transwell assay, and an LDH commercial kit. The surviving and apoptotic cell numbers were examined via flow cytometry and calcein-AM/PI staining. The ultrastructure of the mitochondria was observed, and the concentration of mtDNA was detected via RT-qPCR. A subcutaneous xenograft tumor model in nude mice was established, and pathological staining was used to assess apoptosis and changes in protein expression. Western blotting was used to evaluate the levels of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1)/glutathione peroxidase 4 (GPX4) pathway related proteins and mitochondrial damage-related proteins. Results. CA did not significantly affect FHC viability but was able to reduce CRC cell viability, decrease colony-forming ability, inhibit migration and invasion, and induce apoptosis. CA treatment disrupted mitochondrial morphology and structure and caused a decrease in mitochondrial membrane potential, ATP production, and mtDNA concentration. Treatment with Mito-TEMPO (a mitochondrion-targeted antioxidant) reversed the effects of CA treatment on the above metrics. Furthermore, CA blocked the Nrf2/HO-1/GPX4 pathway, whereas the Nrf2 agonist TBHQ alleviated CA-induced mitochondrial dysfunction. CA treatment decreased the volume and mass of tumor tissue, inhibited cell proliferation, and promoted apoptosis. Notably, CA also led to mitochondrial dysfunction in vivo, which was effectively mitigated by TBHQ. Conclusion. CA blocks the Nrf2/HO-1/GPX4 pathway, causing mitochondrial dysfunction and apoptosis, and thus inhibits the malignant progression of CRC. CA has potential as a therapeutic agent for CRC.
- PublicationOpen AccessExploring the potential application of roxadustat in chronic kidney disease-related osteoporosis based on the regulatory role of HIF-1α in bone metabolism(2026) Shoukui Xiang; Yuexian Xing; Jingru Wang; Biología Celular e Histología; Universidad de Murcia, Departamento de Biologia Celular e HistiologiaOxygen is an essential element in the process of cellular oxidation, and hypoxia, a state of insufficient oxygen, can profoundly influence cellular adaptive responses through gene transcription, thereby impacting cell metabolism, angiogenesis, and inflammation. Hypoxia-inducible factor (HIF), particularly its alpha subunit (HIF-1α), is a critical transcription factor that orchestrates cellular adaptation to hypoxic environments and plays a multifaceted role in various cellular activities. In recent years, HIF-1α has been widely implicated in stimulating hematopoietic function and the good effect of roxadustat in treating renal anemia. However, the specific role of HIF-1α in bone metabolism remains unclear. More and more studies have shown that HIF-1α can not only directly affect osteoblasts, osteoclasts, osteocytes, and bone matrix during bone remodeling, but also locally and remotely regulate macrophages and various cytokines involved in bone remodeling. In addition, HIF-1α can indirectly regulate bone metabolism by promoting angiogenesis and regulating cell metabolism. This review comprehensively elucidates the intricate mechanisms by which HIF-1α influences bone metabolism. The aim is to provide a robust theoretical foundation for exploring the potential therapeutic application of roxadustat to improve bone metabolism in patients with Chronic Kidney Disease-related Osteoporosis (CKD-RO). It is important to note that, while this review highlights promising findings, the current evidence is primarily derived from preclinical animal studies and necessitates rigorous clinical validation.
- PublicationOpen AccessImmunomodulation by collagen VI across fibrotic and tumor microenvironmental contexts(2026) Sharon Gerecht; Jennifer H. Hammel; Biología Celular e Histología; Universidad de Murcia, Departamento de Biologia Celular e HistiologiaThe extracellular matrix (ECM) plays fundamental roles in modulating tissue structure and function under normal and pathological conditions. ECM composition is an essential consideration for studying cellular microenvironments, as varied composition leads to changes in cell behavior and delivery of therapeutics. Collagen VI is a non-fibrillar collagen that is found in both fibrotic and tumor microenvironments, where it promotes disease progression and suppresses the immune system. In this review, we summarize the contributions of collagen VI to fibrosis and tumor progression, followed by a focus on its ability to modulate the immune system in these contexts. Finally, we explore whether collagen VI could be a suitable therapeutic target for future study. While many studies have demonstrated the importance of collagen VI in disease progression, further studies of its immunomodulation abilities are needed to fully realize its potential as a therapeutic target in fibrosis and the tumor microenvironment.
- PublicationOpen AccessEffect of ART1 on the efficacy of oxaliplatin in colorectal cancer under high-cholesterol conditions(2026) Shuxian Zhang; Jing Huang; Qian Gong1; Xingliang Cao; Saiwei Xie; Ming Xiao; Yi Tang; Ming Li; Qingshu LI; Yalan Wang; Xiaodan Chen; Biología Celular e Histología; Universidad de Murcia, Departamento de Biologia Celular e HistiologiaBackground. The growth of colorectal cancer (CRC) can be affected by cholesterol (CHO), which may inhibit the efficacy of oxaliplatin (OXA). A high-fat diet can upregulate phosphorylation by sphingosine kinase 1 (SPHK1)/sphingosine-1-phosphate (S1P)/sphingosine 1 phosphate receptor 1 (S1PR1) and promote tumour cell proliferation. Moreover, S1P activates signal transducer and activator of transcription 3 (STAT3), which plays a critical role in tumour cell proliferation. Knockdown of arginine-specific single ADP ribosyltransferase 1 (ART1) can delay the growth of CRC and promote the inhibitory effect of OXA on CRC cell proliferation. Consequently, in a high-CHO environment, this study aims to investigate the impact of ART1 knockdown in CRC cells treated with OXA and on the growth of transplanted tumours in mice in vivo. Methods. Immunohistochemistry of CRC tissue revealed that, compared with that of normal blood lipids, ART1 expression in CRC tissue from patients with hypercholesterolaemia was higher. Based on CCK8 and EdU assays, we found that ART1 knockdown reduced the proliferation ability of CRC cells and decreased the volume of subcutaneously transplanted tumours in the high-CHO group. Finally, under high-CHO conditions, ART1 knockdown significantly reduced the protein expression levels of SPHK1, S1P, S1PR1, STAT3, and p STAT3 in CT26 cells and transplanted tumours, as determined by western blotting. Results. These findings suggest that under high CHO conditions, inhibition of ART1 expression can promote the inhibitory effect of OXA on CT26 cell proliferation, which may be related to the influence of ART1 on STAT3 expression through SPHK1/S1P/ S1PR1. Conclusions. This study is of great significance in improving the inhibitory effect of OXA on CRC cell proliferation in a high-CHO environment.
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