Juan Yang, Chengli Wen, Ping Li, Mingxiao Yao, Jing Wang
{"title":"Identification of Immune Infiltration-related Molecular Features in Ovarian Cancer Patients and Experimental Validation of Immune Response Molecular Mechanisms through Integrated WGCNA, Machine Learning, and Single-cell Sequencing Analysis.","authors":"Juan Yang, Chengli Wen, Ping Li, Mingxiao Yao, Jing Wang","doi":"10.2174/0115748928297769240611055258","DOIUrl":"https://doi.org/10.2174/0115748928297769240611055258","url":null,"abstract":"<p><strong>Background: </strong>Ovarian cancer is one of the most common gynecological malignancies globally, and immunotherapy has emerged as a promising treatment strategy in recent years. However, the effectiveness of immunotherapy is often limited by immune escape mechanisms.</p><p><strong>Objective: </strong>To unravel the immune response mechanisms in ovarian cancer, this study aimed to employ integrated Weighted Gene Co-expression Network Analysis (WGCNA), machine learning, and single-- cell sequencing analysis to systematically investigate immune infiltration-related molecular features in ovarian cancer patients and experimentally validate the molecular mechanisms of the immune response. This research may provide a new theoretical foundation and treatment strategy for immune-based therapies in ovarian cancer.</p><p><strong>Methods: </strong>Relevant ovarian cancer datasets were collected from public databases. The ConsensusCluster- Plus and ggplot2 R packages were used to perform dimensionality reduction and clustering analysis of immune infiltration-related genes. Various algorithms were employed to select the best ovarian cancer prognostic model with OC consistency. The prognostic value of angiogenesis and immune-related gene expression was evaluated through Kaplan-Meier survival analysis, and the impact of immune infiltration on immune function in ovarian cancer patients was assessed. Functional pathways were identified using the Gene Set Enrichment Analysis (GSEA) method, and the infiltration abundance of immune and stromal components was inferred using the single-sample Gene Set Enrichment Analysis (ssGSEA) method. The influence of angiogenesis on the cellular level of Ovarian Cancer (OC) was explored in single- cell sequencing data, followed by in vitro cell experiments for further validation. The effect of the angiogenesis model on OC was evaluated through the above-mentioned research and experiments, aiming to investigate the mechanism of targeted therapy strategies in ovarian cancer.</p><p><strong>Results: </strong>Immune-related data were collected from ovarian cancer patients in this study. Through WGCNA analysis, the MEturquoise module was identified, and a total of 1018 hub genes were determined. A prediction model was constructed using machine learning, with CoxBoost+StepCox selected as the best model, leading to the identification of 10 genes associated with ovarian cancer. Patients with high AIDPS had shorter survival time, and GSEA analysis revealed enrichment in immune-related pathways. Single-sample gene set enrichment analysis demonstrated increased immune cell infiltration and malignant stromal changes in the high AIDPS group. Results from in vitro cell experiments showed that silencing RPL31 inhibited the proliferation and migration of ovarian cancer cells while enhancing immune response capability.</p><p><strong>Conclusion: </strong>AIDPS holds significant clinical significance in Ovarian Cancer (OC) with poor progn","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141736225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Withdrawn: Fumarate-1 Mediates the Regulation of Mitochondrial Homeostasis by PGC-1α to Promote Cell Pyroptosis and Inhibit the Thyroid Cancer","authors":"Xiaomei Meng, Dong You, Ruizhen Ren","doi":"10.2174/0115748928282936240530105434","DOIUrl":"10.2174/0115748928282936240530105434","url":null,"abstract":"<p><p>Since the authors are not responding to the editor’s requests to fulfill the editorial requirement, therefore, the article has been withdrawn.</p><p><p>Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused.</p><p><p>The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php.</p><p><strong>Bentham science disclaimer: </strong>It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.</p>","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141592507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Siqi Wang, Fang Ji, Xiaoli Gao, Zhiyi Li, Si Lv, Juan Zhang, Jiarui Luo, Dan Li, Jie Yan, Huayang Zhang, Kaicheng Fang, Lin Wu, Miaoling Li
{"title":"Tyrosine Kinase Inhibitor Lenvatinib Causes Cardiotoxicity by Inducing Endoplasmic Reticulum Stress and Apoptosis through Activating ATF6, IRE1α and PERK Signaling Pathways.","authors":"Siqi Wang, Fang Ji, Xiaoli Gao, Zhiyi Li, Si Lv, Juan Zhang, Jiarui Luo, Dan Li, Jie Yan, Huayang Zhang, Kaicheng Fang, Lin Wu, Miaoling Li","doi":"10.2174/0115748928265981231204044653","DOIUrl":"https://doi.org/10.2174/0115748928265981231204044653","url":null,"abstract":"<p><strong>Background: </strong>Lenvatinib is a tyrosine kinase inhibitor that can improve progression-free survival in patients with thyroid cancer and hepatocellular carcinoma. However, it is limited by adverse cardiovascular events, including hypertension and cardiac dysfunction. Activation of endoplasmic reticulum stress is involved in cardiomyocyte apoptosis.</p><p><strong>Objective: </strong>This study aimed to confirm whether the cardiotoxicity of lenvatinib is associated with endoplasmic reticulum stress by targeting the activating transcription factor 6 (ATF6), inositol- requiring enzyme 1α (IRE1α) and protein kinase RNA-like ER kinase (PERK) signaling pathways.</p><p><strong>Methods: </strong>Male C57/BL6 mice were intragastric administration with 30 mg/kg/day lenvatinib. Electrocardiography (ECG) and echocardiography were used to detect arrhythmias and cardiac function. Neonatal rat cardiomyocytes were treated with lenvatinib for 48h. Cell counting kit (CCK8), 2´,7´-dichlorodihydrofluoresceine diacetate (H2DCFHDA), Hoechst 33258 and dihydrorhodamine 123 were respectively used for evaluating cell viability, the level of reactive oxygen species (ROS), nuclear morphological changes and mitochondrial membrane potential (MMP) level.</p><p><strong>Results: </strong>Lenvatinib remarkably decreased the posterior wall thickness of left ventricle during diastole and systole but caused little decrease to the left ventricular ejection fraction (LVEF, %). Furthermore, lenvatinib greatly prolonged the corrected QT interval (QTc) and altered the morphology of cardiomyocytes. No dramatic difference in fibrosis was found in mouse cardiac slices. Lenvatinib upregulates apoptosis-related protein expression. In addition, lenvatinib increased ERS-related protein expression (GRP78, CHOP, and ATF6) and enhanced PERK phosphorylation. In neonatal rat cardiac myocytes, lenvatinib markedly decreased the viability of cardiomyocytes and induced apoptosis. Furthermore, ROS production increased and MMP decreased. Similar to the mice experiment, lenvatinib caused upregulation of apoptosis-related and ERS-related proteins and increased the phosphorylation levels of PERK and IRE1α.</p><p><strong>Conclusion: </strong>Lenvatinib-induced cardiotoxicity is associated with ERS-induced apoptosis by targeting the ATF6, IRE1α, and PERK signaling pathways.</p>","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141592508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Epigallocatechin Gallate Derivative Y6 Reverses Oxaliplatin Resistance in Hepatocellular Carcinoma via Targeting the MiR-338-3p/HIF-1α/TWIST Axis to Inhibit EMT.","authors":"Chuan Huang, Si-Hong Wang, Tao-Tao Liu, Mei-Yi Wu, Kai-Ning Cai, Zhan-Hong Xie, Rui-Qiang Zhao, Yan Wen","doi":"10.2174/0115748928293750240619092747","DOIUrl":"https://doi.org/10.2174/0115748928293750240619092747","url":null,"abstract":"<p><strong>Background: </strong>The emergence of drug resistance to oxaliplatin (OXA) is one of the critical obstacles in the therapy of advanced Hepatocellular Carcinoma (HCC). As an ethyl derivative of the natural compound epigallocatechin gallate (epigallocatechin-3-gallate, EGCG), Y6 was found to be able to enhance the sensitivity of HCC cells to doxorubicin. This study aimed to investigate the effect of Y6 on oxaliplatin resistance in HCC.</p><p><strong>Methods: </strong>MTT was used to determine the reversal effect of Y6 on OXA resistance. To further explore the reversal mechanism, we treated OXA alone or in combination with Y6 or EGCG in drugresistant cells and observed the morphological changes of the cells. At the same time, transwell assay was used to detect the invasion and migration ability of cells. Moreover, Real-time PCR and Western blot analysis were performed to determine the expression levels of the miR-338-3p gene, HIF-1α/Twist proteins, and EMT-related proteins.</p><p><strong>Results: </strong>We found that Y6 could inhibit the proliferation of HCC cells and effectively reverse the drug resistance of oxaliplatin-resistant human liver cancer cells (SMMC-7721/OXA) to OXA, and the reversal effect was more significant than that of its lead drug EGCG. Most of the cells in the control group and OXA group showed typical mesenchymal-like cell morphology, while most of the cells in co-administration groups showed typical epithelioid cell morphology, and the ability of the cells to invade and migrate decreased dramatically, particularly in Y6 plus OXA group. At the same time, Y6 could up-regulate the EMT epithelial marker protein E-cadherin and down-regulate the interstitial marker protein Vimentin. In addition, in co-administration groups, the expression of miR-338-3p was up-regulated, while the expression of HIF-1α and Twist was down-regulated.</p><p><strong>Conclusion: </strong>Y6 significantly enhanced the susceptibility of drug-resistant cells to OXA, and the process may be related to the regulation of miR-338-3p/HIF-1α / TWIST pathway to inhibit EMT. Therefore, Y6 could be considered an effective medication resistance reversal agent, which could improve the therapeutic effect for hepatocellular cancer patients.</p>","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141592506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Radiotherapy Enhancing and Radioprotective Properties of Berberine: A Systematic Review.","authors":"Elham Raeisi, Saeid Heidari-Soureshjani, Catherine Mt Sherwin, Zeinab Bagheri","doi":"10.2174/0115748928315442240624120104","DOIUrl":"https://doi.org/10.2174/0115748928315442240624120104","url":null,"abstract":"<p><strong>Background: </strong>Natural compounds such as Berberine (Ber) have been considered due to favorable anticancer properties, low side effects, and availability along with chemotherapy treatments.</p><p><strong>Objectives: </strong>This study aimed to investigate the radiosensitizing and radioprotective properties of Ber.</p><p><strong>Methods: </strong>In this systematic review that was performed according to PRISMA 2020 guidelines, we searched the publications before 25 Sep 2023 in Web of Science, PubMed, Scopus, Embase, and Cochrane Library databases. After determining inclusion and exclusion criteria, data were extracted and imported into an Excel form, and the results of the studies were reviewed.</p><p><strong>Results: </strong>Ber by reducing the levels of reactive oxygen species (ROS), malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), transforming growth factor-beta 1 (TGF-β1), and increasing interleukin 10 (IL-10) levels, showed its antioxidant and anti-inflammatory properties against ionizing radiation. Reducing cell cytotoxicity and apoptosis were other radioprotective properties of Ber. Conversely, in cancer cells, Ber, via inducing oxidative stress and accumulation ROS in tumor tissues, inducing DNA damage, mitochondrial dysfunction and hyperpolarization, inducing apoptosis, and cell cycle arrest, inhibits the up-regulation of hypoxia-inducible factor-1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF) revealed radiosensitizing properties.</p><p><strong>Conclusion: </strong>Ber, via various mechanisms, showed favorable radioprotective and radiosensitizing properties in clinical and experimental studies. However, more clinical studies are needed in this field.</p>","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141565466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Adhesin Component Member STAG2 Enhances Cisplatin Tolerance in Colorectal Cancer Cells through the Epithelial-Mesenchymal Transition Pathway.","authors":"Pengjun Zhou, Meiyi Ye, Chunlan Chen, Rong Zhang","doi":"10.2174/0115748928305100240613064754","DOIUrl":"https://doi.org/10.2174/0115748928305100240613064754","url":null,"abstract":"<p><strong>Background: </strong>Platinum-based compounds are commonly used as an initial treatment for colorectal cancer (CRC). However, the development of drug resistance in patients with CRC necessitates the administration of high drug concentrations during clinical treatment, thereby augmenting the toxicity of platinum-based compounds and increasing the mortality rate. STAG2 is a significantly associated drug-resistance gene in many cancers, but it has not been studied in colorectal cancer. Therefore, the present study aimed to investigate the role and drug sensitivity of the cisplatin-resistant gene STAG2.</p><p><strong>Methods: </strong>The effects of STAG2 on drug resistance and survival rates of patients with CRC were examined using the Genomics of Drug Sensitivity in Cancer (GDSC) and Kaplan-Meier (KM) plotter databases. Subsequently, a sh-STAG2-HT-29 cell line was generated using a knockdown test of STAG2, and the half-maximal inhibitory concentration (IC50) of the two cell lines was determined using a cell viability test. We then used various techniques, including the Cell Counting Kit-8 (CCK-8), plate cloning, 5-ethynyl-2'-deoxyuridine (EdU) fluorescence staining, flow cytometry for cell cycle detection, the scar assay, the Transwell invasion assay, and Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) fluorescence staining for apoptosis detection, to investigate the functionality of the four subgroups of cancer cell lines. Additionally, Western blotting (WB) was used to identify the potential pathways associated with the observed functional alterations. Finally, the phenotype, tumor weight, mouse weight, tumor volume, and tumor tissue structure of the developed tumors were assessed using the subcutaneous tumor formation method.</p><p><strong>Results: </strong>Database analysis indicated that STAG2 plays a role in facilitating drug resistance among individuals with CRC. Furthermore, mutations in this gene lead to increased sensitivity to cisplatin, and its overexpression was associated with an unfavorable prognosis. Following the successful development of STAG2 knockdown cells, differences in IC50 concentrations were observed between HT-29 and sh-STAG2-HT-29 cells. A treatment concentration of 10 μM cisplatin was selected, and the proliferation, migration, and invasion capabilities of cancer cells decreased after STAG2 knockdown. Additionally, the sensitivity of the cells to cisplatin therapy was increased, which was potentially mediated by the epithelial-mesenchymal transition (EMT) pathway. In mice, the tumorigenic potential of HT-29 cells was reduced by STAG2 knockdown, accompanied by a decrease in resistance to cisplatin therapy.</p><p><strong>Conclusion: </strong>STAG2 acts as a proto-oncogene in CRC, and its resistance to cisplatin therapy is more prominent. This study confirmed the role of STAG2 in CRC and provided a theoretical basis for the further development of STAG2 as an auxiliary criterion for determining ","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141500048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
He Zheng, Siyi Lv, Liqi Lin, Rongrong Li, Lin Li, Yunqing Pang, Jing Wang
{"title":"The Synergistic Anti-tumor Effects of Evodiamine based on Animal Model Experiments: A Systematic Review and Meta-analysis.","authors":"He Zheng, Siyi Lv, Liqi Lin, Rongrong Li, Lin Li, Yunqing Pang, Jing Wang","doi":"10.2174/0115748928303602240610063501","DOIUrl":"https://doi.org/10.2174/0115748928303602240610063501","url":null,"abstract":"<p><strong>Background: </strong>Evodiamine (EVO) is an alkaloid extracted from the dried and nearly ripe fruits of Euodia rutaecarpa and used as an anti-cancer, anti-inflammatory and anti-obesity agent. However, robust evidence of preclinical experiments has been lacking so far. Therefore, the purpose of this article was to investigate the effect of EVO in combination with other treatments on tumors in animal experiments.</p><p><strong>Methods: </strong>A systematic review and meta-analysis were conducted to assess the anti-tumor effect of evodiamine-combined therapy. The search engine and electronic databases included PubMed, Scopus, China Knowledge Resource Integrated Database (CNKI), and SinoMed. The research method was based on the PRISMA checklist.</p><p><strong>Results: </strong>A total of 7 studies and 108 animals were included. As a result, EVO combined therapy was found to be more effective than EVO monotherapy. The SMD was -25.64(95% CI: -5.77 -3.13) in tumor growth. In tumor weight, the SMD was -8.91(95% CI: -16.37, -1.44).</p><p><strong>Conclusion: </strong>EVO has the potential to alleviate the toxicity of chemotherapeutic agents, which increases the translatability to the clinical situation.</p>","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141494714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Patents on PARP-1 Inhibitors for the Management of Cancer from 2017-2023.","authors":"Harshwardhan Singh, Ankit Kumar Singh, Adarsh Kumar, Pradeep Kumar","doi":"10.2174/0115748928315021240603073902","DOIUrl":"https://doi.org/10.2174/0115748928315021240603073902","url":null,"abstract":"<p><strong>Background: </strong>There are eighteen members of the Poly (ADP-ribose) polymerases (PARPs) family, which oversee various cellular processes such as maintaining the integrity of the genome, regulating transcription, cell cycle progression, initiating the DNA damage response, and apoptosis. PARP1 is an essential member of the PARP family and plays a crucial role in repairing single-strand breaks in eukaryotic cells through a process called BER (base excision repair). It is the most extensively studied and commonly found member of this family.</p><p><strong>Area covered: </strong>This article discusses the advancements in developing PARP inhibitors for human cancers. It covers the discovery of new PARP1 inhibitors with chemical classification that selectively target multiple areas using cancer models in vitro and in vivo and evaluates them critically. The focus is on patents that have been published from 2017 to 2023, except tankyrase inhibitors.</p><p><strong>Expert opinion: </strong>PARP1 inhibitors were developed by various companies and academic groups from the 1990s to enhance the effectiveness of chemo and radiotherapy. However, their progress was hindered due to their severe toxicity when combined with these treatments. Therefore, on finding PARP1 inhibitors that can amplify the ability of chemotherapy agents to kill tumors while causing minimal toxicity, these substances can either be used alone as part of the synthetic lethality approach or in conjunction with radiotherapy or chemotherapy, resulting in a mutually beneficial outcome.</p>","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141319411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ruipeng Liang, Zhili Liu, Bo Li, Debing Xiang, Chunrong Wu
{"title":"Regulation of Metastasis and Growth of Colorectal Cancer via Targeting the PTEN Pathway: An Update on the Progress of LncRNA MLLT4-AS1.","authors":"Ruipeng Liang, Zhili Liu, Bo Li, Debing Xiang, Chunrong Wu","doi":"10.2174/0115748928299796240523075219","DOIUrl":"https://doi.org/10.2174/0115748928299796240523075219","url":null,"abstract":"<p><strong>Background: </strong>Globally, colorectal cancer (CRC) is known as the primary cause of mortality. Recent studies have reported that long non-coding RNAs (lncRNAs) are essential in assessing the survival of CRC patients. However, the function of the novel lncRNA MLLT4-AS1 in CRC is still unknown.</p><p><strong>Objective: </strong>This study aimed to identify the expression and the clinical significance of lncRNA MLLT4-AS1 in CRC.</p><p><strong>Methods: </strong>The level of MLLT4-AS1 in CRC was evaluated via the TCGA database. The relative level of MLLT4-AS1 in CRC cell lines was assessed by RT qPCR analysis. In cell culture, HT29 cells were transfected with MLLT4-AS1 siRNA, negative control, overexpressed MLLT4-AS1, or PTEN plasmids. Flow cytometry, CCK 8 assay, wound healing analysis, and transwell assay were used to quantify apoptosis, cell propagation, migration, and invasion, respectively. A nude mouse xenograft model was developed to evaluate the in vivo impact of MLLT4-AS1 plasmids on tumor growth. RNA pull-down analysis was used to search for possible targets of MLLT4-AS1.</p><p><strong>Results: </strong>MLLT4-AS1 was substantially increased in CRC cell lines and patients. It inhibited CRC cell apoptosis and accelerated their proliferative, migration, and invasive properties. In in vivo analysis, MLLT4-AS1 also enhanced the metastasis and proliferation of CRC cells. It was found that PTEN was substantially enriched by biotin-labeled PTEN, as identified via an RNA pull-- down analysis. The expression of phosphatase and PTEN was suppressed by MLLT4-AS1 by ubiquitination proteasome-dependent RNA degradation. Thus, PTEN is considered a potential target of MLLT4-AS1. By targeting PTEN, MLLT4-AS1 intensified the biological behavior of malignant CRC.</p><p><strong>Conclusion: </strong>The study concluded that the MLLT4-AS1/PTEN axis may represent an innovative therapeutic intervention for CRC patients.</p>","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141249217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiangxue Meng, Xinyue Han, Xiangying Lin, Guanhong Li, Jingnan Wang, Ao Sun, Xiaochen Fu, Bowen Xu, Donghua Yang, Yanping Wu, Min Zhang, Xiaoling Fu
{"title":"Construction and Identification of a Human Colorectal Adenoma Epithelial Cell Line by SV40 Large T-Antigen Transfection.","authors":"Xiangxue Meng, Xinyue Han, Xiangying Lin, Guanhong Li, Jingnan Wang, Ao Sun, Xiaochen Fu, Bowen Xu, Donghua Yang, Yanping Wu, Min Zhang, Xiaoling Fu","doi":"10.2174/0115748928297500240522080820","DOIUrl":"https://doi.org/10.2174/0115748928297500240522080820","url":null,"abstract":"<p><strong>Background: </strong>Colorectal adenoma represents the critical step in the development of colorectal cancer. The establishment of an immortalized epithelial cell line of colorectal adenoma of human origin would provide a tool for studying the mechanism of precancerous lesions, screening the efficacy of novel drugs, and constructing in vivo disease models. Currently, there is no commercially available stable supply of epithelial cells from precancerous lesions.</p><p><strong>Aims: </strong>This study aimed to establish a natural LHPP low-expressing precancerous epithelial cell line by SV40-LT antigen gene transfection.</p><p><strong>Methods: </strong>Simian vacuolating virus 40(SV40), SV40-LT overexpressed lentivirus vector, was transfected into primary human colorectal adenomatous polyp epithelial cells. The transfected cells were screened, and the screened cells were amplified to obtain the epithelial cell line: IHCRA- CELL. The cells were identified by morphological observation, cell proliferation, Quantitative real-time PCR (qPCR), and Short Tandem Repeats (STR) experiments. Morphologically, the cells showed epithelial-like characteristics, such as polygon shape, desmosomes mitochondria, and strong positive keratin staining. There was no significant difference between the transfected cells and the primary cells. Through the STR identification experiment, no matching cell lines were found in the cell lines retrieval.</p><p><strong>Conclusion: </strong>We successfully established a natural LHPP low-expressing precancerous epithelial cell line by SV40-LT antigen gene transfection, which has been patented and is now preserved in the Chinese Typical Culture Preservation Center. It was verified that the transformed cells maintained the phenotype and biological characteristics of epithelial cells. This cell line can be used to study the mechanism of precancerous lesions, screen the efficacy of novel drugs, and construct in vivo disease models.</p>","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141162203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}