Experimental cell research最新文献

{"title":"AZD1390, an Ataxia telangiectasia mutated inhibitor, enhances cisplatin mediated apoptosis in breast cancer cells.","authors":"Deniz Özdemir, Can Ali Ağca","doi":"10.1016/j.yexcr.2024.114382","DOIUrl":"10.1016/j.yexcr.2024.114382","url":null,"abstract":"<p><p>Genomic instability is often caused by deficiencies in DNA damage repair pathways, making therapeutic targeting of DDR beneficial for cancer patients with specific DDR functions. ATM kinase plays a critical role in various cellular processes and its deficiency increases sensitivity to DDR-targeted agents in different cancers. Recent studies highlight ATM inhibition as a potential clinical target, with AZD1390 being a notable ATM inhibitor due to its potent and selective inhibition, ability to accumulate at DNA breaks. The study aimed to evaluate the potential anti-cancer effects of AZD1390, a key component of the DNA damage response, in breast cancer cells. The impact of the combination of AZD1390 and cisplatin on various parameters such as cell viability, proliferation, colony formation capacity, DNA damage, reactive oxygen species (ROS) levels, mitochondrial membrane potential, cell cycle progression, and cell death in breast cancer cells was evaluated using several methodologies, including WST-1 assays, real-time cell analysis, colony formation assays, comet assays, DCF-DA, MMP/JC-1 staining assays, flow cytometry along with Western blot analysis. We found that AZD1390 and cisplatin displayed synergistic antitumor effects in breast cancer cells at low doses. Addinationaly exhibited significant anti-proliferative effects in colony formation and real-time cell proliferation experiments, increasing intracellular ROS levels and mitochondrial membrane potential.The combined treatment also arrested the cell cycle at the G2-M point. Furthermore, combination of AZD1390 with cisplatin enhances its apoptotic effects in MCF-7 and MDA-MB-231 cells. These findings could aid in developing new treatments for breast cancer that exploit the genomic instability of cancer cells.</p>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":" ","pages":"114382"},"PeriodicalIF":3.3,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142834858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combined injection of pristane and Bacillus Calmette-Guerin Vaccine successfully establishes a lupus model with atherosclerosis.","authors":"Chunru Jiang, Zhenduo Zhu, Yu Tai, Meiyue Lu, Huijuan Cheng, Tiantian Su, Paipai Guo, Ruhong Fang, Feng He, Mingli Ge, Qiuyun Guan, Yongsheng Han, Shangxue Yan, Wei Wei, Qingtong Wang","doi":"10.1016/j.yexcr.2024.114381","DOIUrl":"10.1016/j.yexcr.2024.114381","url":null,"abstract":"<p><p>Cardiovascular disease (CVD) induced by atherosclerosis (AS) is the main fatal complication of systemic lupus erythematosus (SLE). Establishing an appropriate animal model of SLE with AS is of great value for investigating the pathogenesis and therapeutic targets of SLE-CVD. In the present work, pristane was injected intraperitoneally into C57BL/6J mice to establish the SLE model and Bacillus Calmette-Guerin Vaccine (BCG) was injected intradermally one month later to enhance immunity and induce AS. Both pristane or pristane and BCG treated C57BL/6J mice exhibit a classical lupus-like phenotype which manifested as proteinuria and high levels of serum anti-ANA and anti-dsDNA autoantibodies, in conjunction with pathological changes in spleen and kidney, complement C3 deposition in the kidney, overactivation of T and B cells, a decreased proportion of splenic CD19⁺ B cells, and an increased frequency of CD19^-CD138⁺ plasma cells, CD19⁺CD27⁺ memory B cells, CD3⁺CD4⁺ helper T (Th) cells, and CD3⁺CD4⁺CXCR5⁺PD-1⁺ T follicular helper cells. The combined pristane and BCG challenge aggravated AS in SLE mice, which had an enlarged thymus gland, an increased T cell proliferative vitality, an expanded Th cell pool, severe perivascular lymphocytes, and CD68⁺ macrophage infiltration, in addition to an intimal lipid deposition, and further elevation of Toll-like receptor 2 (TLR2), TLR4, and the transcription factor nuclear factor-κB (NF-κB) expression in kidney tissue and blood vessels when comparing with pristane or BCG injection alone. Pristane combined BCG challenge is able to establish a validated SLE-AS mouse model in C57BL/6J mice.</p>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":" ","pages":"114381"},"PeriodicalIF":3.3,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RPF2 and CARM1 cooperate to enhance colorectal cancer metastasis via the AKT/GSK-3β signaling pathway.","authors":"Cong Cheng, KeMing Zhang, MaCheng Lu, Yuan Zhang, Tong Wang, Ye Zhang","doi":"10.1016/j.yexcr.2024.114374","DOIUrl":"10.1016/j.yexcr.2024.114374","url":null,"abstract":"<p><p>RPF2 plays a crucial role in promoting epithelial-mesenchymal transition (EMT) and regulating metastasis in colorectal cancer (CRC). By analyzing data from the TCGA and GEO databases, we observed significantly elevated RPF2 expression in CRC, which correlated with EMT markers. Further investigations using stable RPF2 overexpression and knockdown cell lines demonstrated that RPF2 facilitates EMT activation through the AKT/GSK-3β signaling pathway. Notably, CARM1 was identified as a key downstream effector of RPF2. Selective inhibition of CARM1 effectively suppressed the activation of the AKT/GSK-3β pathway and EMT induced by RPF2 overexpression. Both in vitro and in vivo experiments confirmed that RPF2 expression levels positively correlate with the metastatic potential of CRC cells. Moreover, treatment with a CARM1 inhibitor significantly reduced the invasive and migratory capabilities of RPF2-overexpressing cells. These findings suggest that RPF2 drives CRC metastasis by modulating EMT via the AKT/GSK-3β pathway, with CARM1 serving as a critical mediator, offering potential therapeutic targets for CRC.</p>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":" ","pages":"114374"},"PeriodicalIF":3.3,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomes derived from cardiac fibroblasts with Ang-II stimulation provoke myocardial hypertrophy via miR-15b-5p/PTEN-L axis.","authors":"Zhiwen Hu, Dijiu Xiao, Liang Wang, Jiaxiang You, Tao Long, Jinping Wang, Yibiao Shang, Dasong Yi, Lu Ding, Xiang Wang, Xiaoping Peng, Junyi Zeng","doi":"10.1016/j.yexcr.2024.114380","DOIUrl":"10.1016/j.yexcr.2024.114380","url":null,"abstract":"<p><p>This study aimed to examine the impact of exosomes derived from Ang II-stimulated cardiac fibroblasts (CFs) on myocardial hypertrophy. Neonatal rat CFs were isolated and identified using Vimentin immunofluorescence. Following Ang II stimulation, exosomes were collected, characterized, and subjected to miRNA sequencing. Myocardial hypertrophy models were induced both in vitro and in vivo using Ang II. CFs were transfected with miR-15b-5p mimics or inhibitors, and their exosomes were co-cultured with rat cardiomyocytes (H9C2). Changes in cell viability, myocardial hypertrophy, and the expression levels of PTEN-L, PINK1, and Parkin proteins were assessed using the CCK-8 assay, cell surface area evaluation, and Western blot analysis. Cardiac tissue pathology and myocardial hypertrophy were evaluated through HE and WAG staining, respectively, while PTEN-L expression was detected by immunohistochemistry. The results demonstrated successful isolation of CFs and their exosomes, with miR-15b-5p significantly enriched in the exosomes derived from Ang II-stimulated CFs (Ang II-CFs-Exos). Ang II-CFs-Exos inhibited cell viability, exacerbated myocardial hypertrophy, and activated mitophagy via miR-15b-5p in the in vitro myocardial hypertrophy model. PTEN-L was identified as a downstream target of miR-15b-5p, with its overexpression reversed the effects of miR-15b-5p mimic on myocardial hypertrophy and mitophagy. Additionally, mitochondrial inhibitors also countered the effects of the miR-15b-5p mimic on myocardial hypertrophy. Furthermore, Ang II-CFs-Exos exacerbated myocardial hypertrophy in rats, while knockout of miR-15b-5p in Ang II-CFs-Exos mitigated this effect. To sum up, Ang II-CFs-Exos promote myocardial hypertrophy by modulating PINK1/Parkin signaling -mediated mitophagy through the miR-15b-5p/PTEN-L axis.</p>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":" ","pages":"114380"},"PeriodicalIF":3.3,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of THBS1 axis contributes to the antitumor effect of PA-MSHA in anaplastic thyroid cancer.","authors":"Zhe Li, Ting He, Zhichao Xing, Jingqiang Zhu, Wenshuang Wu, Anping Su","doi":"10.1016/j.yexcr.2024.114373","DOIUrl":"10.1016/j.yexcr.2024.114373","url":null,"abstract":"<p><p>Anaplastic thyroid cancer (ATC) is the most aggressive form of thyroid cancer, has the worst prognosis, and lacks effective treatment in clinical practice. Thrombospondin-1 (THBS1) is a multifunctional extracellular matrix (ECM) glycoprotein that regulates cell proliferation, apoptosis, and metastasis, and is considered a potential clinical biomarker for the monitoring and prognostication of various tumors. However, the specific roles and molecular mechanisms of action of THBS1 in ATC remain unclear. In this study, we found that Pseudomonas aeruginosa-mannose sensitive hemagglutinin (PA-MSHA), a THBS1 inhibitor, significantly inhibited ATC tumor growth both in vitro and in vivo. Mechanistically, we demonstrated that THBS1 was the target gene of PA-MSHA in ATC and identified the THBS1/FAK/AKT axis as the key antitumor signaling pathway. Furthermore, we confirmed that THBS1 was overexpressed in ATC tumors and that high levels of THBS1 were associated with a poorer prognosis in thyroid cancer. Silencing THBS1 significantly decreased p-FAK and p-AKT levels, resulting in significant inhibition of cell proliferation and apoptosis in ATC cells. These findings suggest that the THBS1/FAK/AKT axis is a promising therapeutic target for ATC treatment.</p>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":" ","pages":"114373"},"PeriodicalIF":3.3,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tripartite motif (TRIM) proteins roles in the regulation of immune system responses: Focus on autoimmune diseases.","authors":"Subasini Uthirapathy, Abdulrahman T Ahmed, Mahmood Jawad, Vicky Jain, Suhas Ballal, Hussein Riyadh Abdul Kareem Al-Hetty, Gaurav Khandelwal, Renu Arya, Muthena Kariem, Yasser Fakri Mustafa","doi":"10.1016/j.yexcr.2024.114379","DOIUrl":"10.1016/j.yexcr.2024.114379","url":null,"abstract":"<p><p>The tripartite motif (TRIM) proteins are well-studied as essential modulators of many processes, including the modulation of several pathways linked to immunological reactions. Most TRIM family members can polyubiquitinate the targeted proteins by acting as E3 ubiquitin ligases. According to current research, TRIMs play a critical role in innate immune response via modifying transcription factors, pattern recognition receptors (PRRs), and key adaptor proteins within innate immunity. It is becoming clearer that TRIMs play important roles in adaptive immune response, especially in the stimulation and promotion of T cells. We highlight the E3 ubiquitin ligase functions of TRIMs in the PRRs axis linked to autoimmune disorders. By focusing on TRIM family members, we also clarify the new approaches to regulating immunological reactions to alleviate autoimmunity.</p>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":" ","pages":"114379"},"PeriodicalIF":3.3,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SEMA3C promotes thyroid cancer via the Wnt/β-catenin pathway.","authors":"Shiwei Li, Yanmei Cheng, Changhui Gao, Qingling Yuan, Xiubo Lu","doi":"10.1016/j.yexcr.2024.114378","DOIUrl":"10.1016/j.yexcr.2024.114378","url":null,"abstract":"<p><p>Semaphorin 3C (SEMA3C) regulates the progression of several tumors. However, the role of SEMA3C in thyroid cancer remains unknow. In the present study, SEMA3C was overexpressed or knocked down in thyroid cancer cell lines BCPAP and IHH-4. It was found that SEMA3C promoted the cell migration, invasion, and mesenchymal-epithelial transition (EMT) process. SEMA3C overexpression enhanced tumor cell stemness, while SEMA3C knockdown showed the opposite effects. In vivo experiments suggested that SEMA3C accelerated the tumor growth and metastasis. Moreover, SEMA3C enhanced β-catenin nuclear translocation. When cells were treated with Dickkopf-1 (DKK1), an inhibitor of Wnt/β-catenin pathway, the promoting effects of SEMA3C on cell migration and stemness were offset. Wnt/β-catenin pathway mediated the roles of SEMA3C in thyroid cancer. Additionally, an upstream regulator of SEMA3C was identified. E1A binding protein P300 (P300) was found to increase the histone three lysine 27 acetylation (H3K27ac) level of SEMA3C, promoting its transcriptional activation. Therefore, we clarify that SEMA3C exerts a tumor-promoting effect on thyroid cancer, and Wnt/β-catenin pathway is the critical downstream pathway.</p>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":" ","pages":"114378"},"PeriodicalIF":3.3,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nucleostemin interacts with SMAD3 promoting tumor metastasis.","authors":"Xuling Sun, Jiageng He, Yujiang Li, Zhiqiang Chu, Lei Zhu, Hui Zhang, Xiangwei Wu","doi":"10.1016/j.yexcr.2024.114362","DOIUrl":"10.1016/j.yexcr.2024.114362","url":null,"abstract":"<p><p>SMAD3 plays a crucial role in TGF-β, regulating various normal developmental mechanisms and disease pathogenesis. Here, we report that SMAD3 directly interacts with Nucleostemin (NS), leading to nuclear translocation and affecting SMAD3 activity after TGF-β1 stimulation. Moreover, NS acts as a competitor, preventing PPM1A from recognizing and dephosphorylating SMAD3. Experimental investigations have demonstrated that NS significantly enhances cellular migration and invasion by promoting the EMT mechanism in vitro. NS knockdown notably suppresses tumor metastasis in the lungs and liver in vivo. Importantly, NS expression is significantly elevated in numerous human malignancies, correlating with a poorer prognosis. The collective evidence from these studies suggests that NS exhibits oncogenic characteristics, supporting further exploration of NS as a potential target for tumor treatment.</p>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":" ","pages":"114362"},"PeriodicalIF":3.3,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Small RNA sequencing of differentiated astrocytoma exposed to NMOSD patient sera reveals perturbations in neurodegenerative signaling.","authors":"Pallavi Chatterjee, Shouvik Chakravarty, Nidhan K Biswas, Santosh Trivedi, Ashis Datta, Debashis Mukhopadhyay","doi":"10.1016/j.yexcr.2024.114375","DOIUrl":"10.1016/j.yexcr.2024.114375","url":null,"abstract":"<p><p>The signaling pathways behind severe astrocytic lysis with Aquaporin4 auto-antibody (AQP4-IgG) seropositivity, and reactive astrocytosis with myelin oligodendrocyte glycoprotein auto-antibody (MOG-IgG) seropositivity, remain largely unexplored in Neuromyelitis optica spectrum disorder (NMOSD), while almost no molecular details being known about double-seronegative (DN) patients. Recent discovery of glial fibrillary acidic protein (GFAP) in DN NMOSD patients' cerebrospinal fluid, akin to AQP4-IgG + ve cases, suggests astrocytopathy. Here, we aim to study small non coding RNA (sncRNA) signature alterations in astrocytes exposed to AQP4-IgG + ve and MOG-IgG + ve patient sera, and their potential resemblance with DN-NMOSD. Next Generation Sequencing (NGS) revealed differential expression of several microRNAs with notable alterations in hsa-miR-6824-3p, hsa-miR-324-5p and hsa-miR-4466 respectively upon sera treatment. Results with DN-NMOSD patient sera are majorly similar to that of AQP4+ve sera. Strikingly, in all three treatments, hsa-miR-200b-3p was significantly upregulated. Functional enrichment analysis revealed that Hippo and FoxO signaling pathways were primarily impacted in AQP4-IgG + ve and double negative sera treated cells whereas, MOG-IgG + ve sera treatment perturbed the PI3K-Akt and MAPK signaling pathways. Furthermore, NGS also revealed differential expression of several piRNAs in cells upon treatment with AQP4-IgG + ve and MOG-IgG + ve sera and VEGF signaling was identified as the common target of differentially expressed piRNAs of both the groups. This study, for the first time, revealed that the molecular pathophysiology of double-seronegative NMOSD might involve astrocytopathy akin to AQP4+ve NMOSD, thus pointing towards the possible existence of unidentified astrocytic autoimmune targets and identified the major alterations in intracellular sncRNAs and the associated overall cellular signaling pathways that potentially contribute to the fate of astrocytes during the progression of the disease.</p>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":" ","pages":"114375"},"PeriodicalIF":3.3,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Paradigm shift: microRNAs interact with target gene promoters to cause transcriptional gene activation or silencing.","authors":"Neelanjana Sarkar, Arun Kumar","doi":"10.1016/j.yexcr.2024.114372","DOIUrl":"10.1016/j.yexcr.2024.114372","url":null,"abstract":"<p><p>MicroRNAs (miRNAs/miRs) are small (18-25 nucleotides in length), endogenous, non-coding RNAs that typically repress gene expression by interacting with the 3'untranslated regions (3'UTRs) of target mRNAs in the cytoplasm. While most of the scientific community still views miRNAs as repressors of gene expression, this review highlights their non-canonical novel role in the nucleus as activators or silencers of target gene transcription through miRNA-promoter interaction. The mechanistic details of the transcriptional role of miRNAs are yet to be elucidated, however, they can be explained by prospective models. In this review, we aim to discuss the different examples of transcriptional regulation by miRNAs and their possible mechanism of action, thereby offering a comprehensive perspective on the role of miRNAs in gene regulation and their importance in health and diseases.</p>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":" ","pages":"114372"},"PeriodicalIF":3.3,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}