Xiao-Xia Chi, Peng Ye, Neng-Qi Cao, Wei-Lun Hwang, Jong-Ho Cha, Mien-Chie Hung, Kai-Wen Hsu, Xiu-Wen Yan, Wen-Hao Yang
{"title":"PPIH as a poor prognostic factor increases cell proliferation and m6A RNA methylation in hepatocellular carcinoma.","authors":"Xiao-Xia Chi, Peng Ye, Neng-Qi Cao, Wei-Lun Hwang, Jong-Ho Cha, Mien-Chie Hung, Kai-Wen Hsu, Xiu-Wen Yan, Wen-Hao Yang","doi":"10.62347/NZIJ5785","DOIUrl":"https://doi.org/10.62347/NZIJ5785","url":null,"abstract":"<p><p>RNA-binding proteins (RBPs) play a crucial role in the biological processes of liver hepatocellular carcinoma (LIHC). Peptidyl-prolyl cis-trans isomerase H (PPIH), an RBP, possesses prolyl isomerase activity and functions as a protein chaperone. The relationship between PPIH and LIHC has not yet been fully elucidated. This study elucidated potential mechanisms through which PPIH affects the prognosis of LIHC. Bioinformatics analysis and in vitro experiments revealed that PPIH expression was higher in LIHC tissues than in normal tissues. PPIH was identified as an independent prognostic factor, with high PPIH expression being associated with worse prognoses. Moreover, PPIH increased the m6A RNA methylation level and promoted cell proliferation by modulating DNA replication and the expression of cell cycle-related genes in LIHC cells. Bioinformatics analysis also revealed that PPIH expression increased immune cell infiltration and the expression of immune checkpoint proteins. Collectively, these findings indicate that PPIH might promote LIHC progression by enhancing the m6A RNA methylation level, increasing cell proliferation, and altering the tumor immune microenvironment. Our study demonstrates that PPIH, as a poor prognostic factor, may lead to LIHC malignancy through multiple pathways. Further in-depth research on this topic is warranted.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"14 8","pages":"3733-3756"},"PeriodicalIF":3.6,"publicationDate":"2024-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11387852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ashiq Ali, Saba Manzoor, Tayyab Ali, Muhammad Asim, Ghulam Muhammad, Aftab Ahmad, Mohamad Ikhwan Jamaludin, Sutha Devaraj, Nayla Munawar
{"title":"Innovative aspects and applications of single cell technology for different diseases.","authors":"Ashiq Ali, Saba Manzoor, Tayyab Ali, Muhammad Asim, Ghulam Muhammad, Aftab Ahmad, Mohamad Ikhwan Jamaludin, Sutha Devaraj, Nayla Munawar","doi":"10.62347/VUFU1836","DOIUrl":"https://doi.org/10.62347/VUFU1836","url":null,"abstract":"<p><p>Recent developments in single-cell technologies have provided valuable insights from cancer genomics to complex microbial communities. Single-cell technologies including the RNA-seq, next-generation sequencing (NGS), epigenomics, genomics, and transcriptomics can be used to uncover the single cell nature and molecular characterization of individual cells. These technologies also reveal the cellular transition states, evolutionary relationships between genes, the complex structure of single-cell populations, cell-to-cell interaction leading to biological discoveries and more reliable than traditional bulk technologies. These technologies are becoming the first choice for the early detection of inflammatory biomarkers affecting the proliferation and progression of tumor cells in the tumor microenvironment and improving the clinical efficacy of patients undergoing immunotherapy. These technologies also hold a central position in the detection of checkpoint inhibitors and thus determining the signaling pathways evoked by tumor invasion. This review addressed the emerging approaches of single cell-based technologies in cancer immunotherapies and different human diseases at cellular and molecular levels and the emerging role of sequencing technologies leading to drug discovery. Advancements in these technologies paved for discovering novel diagnostic markers for better understanding the pathological and biochemical mechanisms also for controlling the rate of different diseases.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"14 8","pages":"4028-4048"},"PeriodicalIF":3.6,"publicationDate":"2024-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11387862/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Integrative analysis of autophagy-related genes reveals that CAPNS1 is a novel prognostic biomarker and promotes the malignancy of melanoma via Notch signaling pathway.","authors":"Mengru Gao, Jisong Liu, Miaomiao Yang, Xiangzhou Zhang, Yulian Zhang, Zhuliang Zhou, Jiabin Deng","doi":"10.62347/ECDF2762","DOIUrl":"https://doi.org/10.62347/ECDF2762","url":null,"abstract":"<p><p>Skin cutaneous melanoma (SKCM) is a highly fatal form of skin cancer that develops from the malignant transformation of epidermal melanocytes. There is substantial evidence linking autophagy to cancer etiology and immunotherapy efficacy. This study aimed to conduct a comprehensive analysis of autophagy-related genes (ARGs) using TCGA datasets and further explore the potential function of critical ARGs in SKCM progression. We performed comprehensive bioinformatics analysis uses the TCGA dataset. RT-PCR was applied to examine the expression of CAPNS1 in SKCM cells. Lost-of-function experiments were performed to detect the expression of the related proteins. In this search, we screed 70 differentially expressed autophagy-related genes (DE-ARGs), including 33 up-DE-ARGs and 37 down-DE-ARGs. Enrichment assays revealed that these 70 DE-ARGs may exert influence on critical cellular processes such as autophagy, protein kinase activity, and signaling pathways, impacting cell growth, differentiation, survival, and tumor development. Then, we further explore the prognostic value of 70 DE-ARGs and confirmed 18 survival-related DE-ARGs in SKCM patients. Nearly all the 18 DE-ARGs' methylation was negatively correlated with their corresponding expression in SKCM. The 12 survival-related DE-ARGs were used to develop a unique predictive model that effectively classified SKCM patients into high- and low-risk groups with regard to overall survival. Furthermore, tumor environment analysis indicated that the risk score was associated with several immune cells. Among the 12 survival-related DE-ARGs, our attention focused on CAPNS1 which was highly expressed in SKCM patients and predicted a poor prognosis. In addition, we confirmed that knockdown of CAPNS1 distinctly suppressed the proliferation, metastasis and EMT of SKCM cells, and promoted autophagy via regulating Notch signaling pathway. Overall, this study enhances our understanding of the intricate molecular landscape of SKCM progression and presents promising avenues for future research and clinical applications.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"14 8","pages":"3665-3693"},"PeriodicalIF":3.6,"publicationDate":"2024-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11387868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bin Wang, Xiaobo Peng, Jie Li, Yiran Wang, Longpei Chen, Meihong Wu, Yingyi Zhang, Wei Wang, Dan Feng, Shuhui Tang, Linli Zhang, Xianbao Zhan
{"title":"Personalized mRNA vaccine combined with PD-1 inhibitor therapy in a patient with advanced esophageal squamous cell carcinoma.","authors":"Bin Wang, Xiaobo Peng, Jie Li, Yiran Wang, Longpei Chen, Meihong Wu, Yingyi Zhang, Wei Wang, Dan Feng, Shuhui Tang, Linli Zhang, Xianbao Zhan","doi":"10.62347/NVFB3780","DOIUrl":"https://doi.org/10.62347/NVFB3780","url":null,"abstract":"<p><p>Therapeutic cancer vaccines are valuable tools for educating the immune system to fight tumors precisely. Cancer cells are characterized with genetic instability and abundant somatic mutations, leading to the production of tumor specific antigens (TSA) called neoantigens. The main goal of neoantigen-based cancer vaccines is to activate the immune system and elicit effective tumor-specific T-cell responses. There have been no reports of advanced esophageal squamous cell carcinoma (ESCC) cases achieving partial remission after personalized mRNA (messenger RNA) vaccine treatment. As personalized neoantigen-based immunotherapies are emerging, here we report a 67-year-old male patient diagnosed with ESCC and multiple enlarged mediastinal lymph nodes, where mRNA vaccines were used for the first time. Tissue samples from the recurrence focus in the esophagus were subjected to whole transcriptome sequencing. The neoantigens were identified by bioinformatics analyses. The top 20 neoantigens were selected to compose the polyneoantigen vaccine, which were administered at 1 mg every 3 weeks for 4 cycles in combination with a PD-1 (programmed death-1) inhibitor. The patient was boosted with a single dose of the PD-1 inhibitor 8 weeks after the 4th cycle. In addition, immune responses were evaluated before and after the 4 cycles of vaccine therapy, and the lesions were evaluated by imaging examination. Our results revealed that neoantigen-based vaccines significantly activated the tumour-specific immune response. TCR (T cell receptor) V-J pairing analysis showed an increase in the abundance of oligoclonal TCRs, indicating improved homogeneity. No grade 3 or higher drug-related adverse events were observed, except for grade 4 thrombocytopenia caused by PD-1 inhibitor treatment. The patient achieved a partial response (PR), with a progression-free survival (PFS) time of 457 days, the OS (overall survival) time of 457 days, and DOR (duration of response) of 377 days. Our report suggests that combining the personalized mRNA vaccine therapy with PD-1 blockade therapy may be an effective treatment strategy for patient with advanced esophageal cancer. However, further clinical trials are necessary to confirm the efficacy and safety of personalized neoantigen-based immunotherapies in the treatment of advanced ESCC. This trial is registered with ClinicalTrials.gov, NCT03468244 on March 16, 2018, and is now complete.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"14 8","pages":"3896-3904"},"PeriodicalIF":3.6,"publicationDate":"2024-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11387870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Targeted multimodal synergistic therapy of drug-resistant HER2-positive breast cancer by pyrotinib-ICG self-assembled nanoparticles.","authors":"Juncheng Xuhong, Nisha Wu, Qiyun Shi, Hao Tian, Zaihui Peng, Jun Jiang, Jing Zhang, Xiaowei Qi","doi":"10.62347/JZRN6919","DOIUrl":"https://doi.org/10.62347/JZRN6919","url":null,"abstract":"<p><p>Neoadjuvant targeted therapy combining targeted agents with chemotherapy significantly improve survival rates of patients suffering from human epidermal receptor (HER2)-positive breast cancer (BC) in early or locally advanced stages. However, approximately 50% of patients fail to achieve a pathological complete response. In response, targeted photothermal therapy (PTT) and photodynamic therapy (PDT) have emerged as effective strategies to bolster primary tumors treatment. In this context, we developed a novel nanodrug, referred to as \"P/ICG\", which comprised of a tyrosine-kinase inhibitor pyrotinib and the photosensitizer indocyanine green (ICG). This formulation was created for the targeted and multimodal synergistic therapy of HER2-positive BC. Upon irradiation with near-infrared light, ICG generates high levels of intracellular reactive oxygen species and elevated temperature, enhancing chemotherapy effects of pyrotinib. This synergistic action boosts a highly effective anticancer effect promoting the ferroptosis pathway, providing an efficient therapeutic strategy for treating HER2-positive BC.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"14 8","pages":"3976-3993"},"PeriodicalIF":3.6,"publicationDate":"2024-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11387853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wei-Bo Tang, Wen-Hang Wang, Hyoung Jae Lee, Jie Zhou, Xu-Ben Yu, Quan Zhou, Sayeon Cho, Kwonseop Kim
{"title":"δ-catenin promotes Twist1 stabilization in prostate cancer through ubiquitination modification.","authors":"Wei-Bo Tang, Wen-Hang Wang, Hyoung Jae Lee, Jie Zhou, Xu-Ben Yu, Quan Zhou, Sayeon Cho, Kwonseop Kim","doi":"10.62347/ALJT8663","DOIUrl":"https://doi.org/10.62347/ALJT8663","url":null,"abstract":"<p><p>Prostate cancer generally has a high long-term survival rate; however, metastatic prostate cancer remains largely incurable despite intensive multimodal therapy. Recent research has identified δ-catenin, a member of the catenin family, as playing a crucial role in the progression of prostate cancer. Nonetheless, the extent to which δ-catenin influences transcription factors associated with epithelial-mesenchymal transition (EMT) has not been thoroughly explored. This study aims to investigate the hypothesis that δ-catenin enhances the stability of Twist1, thereby promoting the migratory and invasive capabilities of prostate cancer cells. Clinical data indicate a strong correlation between δ-catenin and Twist1 expression levels. Western blot analysis confirmed that δ-catenin stabilizes Twist1 and induces ectopic expression. Additionally, δ-catenin was found to reduce Twist1 phosphorylation by inhibiting GSK-3β activity. Immunoprecipitation analysis suggested that δ-catenin exerts its effect by competing with Twist1 for binding to ubiquitin (Ub). These results highlight the role of δ-catenin in the ubiquitination modification of Twist1, suggesting that the combined presence of δ-catenin and Twist1 could serve as a biomarker for tumor progression in prostate cancer.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"14 8","pages":"3773-3788"},"PeriodicalIF":3.6,"publicationDate":"2024-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11387878/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Gastric adenocarcinoma with intestinal progenitor cell differentiation: a morphologically underdiagnosed and more invasive distinctive type of gastric adenocarcinoma.","authors":"Xian Ge, Meiling Hua, Yuan Zhan","doi":"10.62347/RRHG4189","DOIUrl":"https://doi.org/10.62347/RRHG4189","url":null,"abstract":"<p><p>This study aims to explore the clinical and pathological characteristics, prognosis, diagnosis, and differential diagnosis of gastric adenocarcinoma with enteroblastic differentiation (GAED) in elderly patients. A total of 16 cases of GAED diagnosed from August 2019 to August 2022 at the First Affiliated Hospital of Nanchang University were retrospectively collected to analyze their clinical and pathological features. A control group of 360 cases of conventional gastric adenocarcinoma diagnosed during the same period was used for comparison. Among the 16 GAED patients, 11 were male and 5 were female, with ages ranging from 64 to 89 years (median age 75.5 years). Clinical manifestations of these patients included symptoms such as abdominal pain, bloating, hematemesis, and melena. The macroscopic classification revealed 11 cases of ulcerative lesions, 4 protruded lesions, and 1 diffusely infiltrative lesion. Tumor sizes varied from 3 to 9.5 cm in diameter, with a median diameter of 4.75 cm. Microscopically, the tumor cells exhibited tubular, papillary, and cribriform arrangements, with cuboidal or columnar morphology, relatively distinct cell boundaries, and cytoplasm that appeared clear or weakly acidophilic. Immunophenotyping analysis revealed the expression of SALL4 (15/16), Glypican-3 (12/16), CDX2 (12/16), CD10 (10/16), and p53 (12 cases exhibiting mutant expression, 4 cases exhibiting wild-type expression) within the tumor cells. There was no loss of mismatch repair proteins (MLH1, PMS2, MSH2, MSH6). The Ki-67 proliferation index ranged from 50% to 95%. In comparison to conventional gastric adenocarcinoma, GAED was frequently found in the gastric antrum (P<0.001) and exhibited a higher incidence of intravascular cancer emboli (P<0.001). Significant differences were noted in the Lauren classification, invasion depth, differentiation degree (P<0.01), and macroscopic type (P<0.05). However, no significant differences were found regarding age, gender, tumor diameter, neural invasion, or lymph node metastasis (P>0.05). The postoperative follow-up ranging from 5 to 29 months revealed one death and 15 cases of disease-free survival. GAED is a special subtype of gastric adenocarcinoma characterized by a combination of embryonal and intestinal differentiation immunophenotypes, as well as its increased propensity for biological invasion. Accurate identification of GAED is crucial in pathological practice, as it helps differentiate between GAED and conventional adenocarcinoma and aids in the evaluation of tumor malignancy. Furthermore, it is imperative to conduct a differential diagnosis that involves hepatoid adenocarcinoma, yolk sac tumor-like adenocarcinoma, and metastatic hepatocellular carcinoma.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"14 8","pages":"3885-3895"},"PeriodicalIF":3.6,"publicationDate":"2024-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11387865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Nuclear factor-erythroid 2-related factor 3 (NRF3) is low expressed in colorectal cancer and its down-regulation promotes colorectal cancer malignance through activating EGFR and p38/MAPK [Retraction].","authors":"","doi":"10.62347/VVLN6538","DOIUrl":"https://doi.org/10.62347/VVLN6538","url":null,"abstract":"<p><p>[This retracts the article on p. 511 in vol. 9, PMID: 30949407.].</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"14 8","pages":"4112"},"PeriodicalIF":3.6,"publicationDate":"2024-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11387851/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"PCMT1 confirmed as a pan-cancer immune biomarker and a contributor to breast cancer metastasis.","authors":"Yiqi Liu, Haobing Li, Xiangyu Shen, Ying Liu, Xiaoxiao Zhong, Jing Zhong, Renxian Cao","doi":"10.62347/TYLL7952","DOIUrl":"https://doi.org/10.62347/TYLL7952","url":null,"abstract":"<p><p>Protein L-isoaspartyl (D-aspartyl) methyltransferase (PIMT, gene name PCMT1) is an enzyme that repairs proteins with altered aspartate residues by methylation, restoring their normal structure and function. This study conducted a comprehensive analysis of PCMT1 in pan-cancer. The Cancer Genome Atlas, Human Protein Atlas website, and the Genotype-Tissue Expression were utilized in analysis of PCMT1 expression. We examined the association between PCMT1 expression and various factors, including gene modifications, DNA methylation, immune cell infiltration, immunological checkpoints, drug susceptibility, tumor mutation burden (TMB), and microsatellite instability (MSI). Enrichment analyses determined the potential biological roles and pathways involving PCMT1. Our focus then shifted to the role of PCMT1 in breast invasive carcinoma (BRCA). We found that PCMT1 expression was aberrant in many tumors and significantly influenced the prognosis across several cancer types. Gene alterations in PCMT1 predominantly involved deep deletions and amplifications. A negative correlation was observed between DNA methylation and PCMT1 expression across all studied cancer types except thyroid carcinoma PCMT1 exhibited positive correlations with common lymphoid progenitor and CD4(+) T helper 2 cells, whereas it was inversely correlated with central and effector memory T cells, memory CD8(+) T cells, and CD4(+) T helper 1 cells. In many cancer types, PCMT1 expression closely correlated with immunological checkpoint inhibitors, TMB, and MSI. It was also significantly linked to pathways involved in epithelial-mesenchymal transition (EMT), highlighting its role in cancer metastasis. PCMT1 emerged as a significant predictor of breast cancer progression. In vitro experiments demonstrated that reducing PCMT1 expression decreased BRCA cell migration and invasiveness. Additionally, animal studies confirmed that inhibition of PCMT1 slowed tumor growth.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"14 8","pages":"3711-3732"},"PeriodicalIF":3.6,"publicationDate":"2024-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11387850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Screening for the presence of aberrantly expressed ACTR2 in osteosarcoma and analyzing its mechanism of action through an online database.","authors":"Min Yi, Kai Zheng, Qian Ning, Yu Nie, Fuguo Huang","doi":"10.62347/XMFC4884","DOIUrl":"https://doi.org/10.62347/XMFC4884","url":null,"abstract":"<p><p>Osteosarcoma (OS) represents the most prevalent malignant bone tumor clinically, significantly impacting the health and safety of patients. The exploration of molecular pathogenic mechanisms is deemed a breakthrough for OS diagnosis and treatment. Within the GSE16088 dataset, a total of 1,948 differentially expressed genes (DEGs) were identified, comprising 1,697 down-regulated and 251 up-regulated genes. Notably, only two DEGs were associated with the response to trichostatin A: ARP2 actin-related protein 2 homolog (ACTR2) and MEF2C; ACTR2 garnered particular interest. Subsequently, 57 OS patients (research group) and 50 healthy controls from the same period (control group) were selected for analysis. The expression of ACTR2 in peripheral blood in both groups, as well as its levels in cancerous tissues and adjacent counterparts of OS patients, were evaluated, ascertaining the correlation between ACTR2 and OS. OS cases exhibited lower levels of ACTR2 compared to controls (P<0.05), with ACTR2 expression demonstrating a robust diagnostic capability for OS. Similarly, ACTR2 expression was diminished in cancer tissues (P<0.05). A three-year prognostic follow-up was conducted to assess the prognostic value of ACTR2 in OS patients. The follow-up findings revealed a significantly lower survival rate among patients with low ACTR2 expression in contrast to those with high expression (P<0.05). In vitro studies involved the construction of abnormal expression vectors for ACTR2 and miR-374a-5p, which were transfected into human OS cells (U2OS, SAOS). The outcomes indicated that elevating ACTR2 or suppressing miR-374a-5p attenuated the proliferative, invasive, and migratory capacities as well as the epithelial-mesenchymal transition (EMT) of OS cells while enhancing their apoptosis. Conversely, upregulation of miR-374a-5p yielded opposing effects (P<0.05). The dual-luciferase reporter (DLR) assay demonstrated that the fluorescence activity of ACTR2-WT was significantly inhibited by the miR-374a-5p mimic sequence (P<0.05), confirming the presence of a targeted regulatory relationship between ACTR2 and miR-374a-5p. These findings offer novel insights for future research directions in the diagnosis and treatment of OS.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"14 8","pages":"4065-4081"},"PeriodicalIF":3.6,"publicationDate":"2024-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11387873/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}