MedComm – Oncology最新文献

{"title":"Comprehensive analysis of cuproptosis-related gene expression and positive correlations with CD4+ T cell infiltration in head and neck squamous cell carcinoma","authors":"Zhangwei Hu,&nbsp;Wenbin Lei,&nbsp;Weiping Wen","doi":"10.1002/mog2.42","DOIUrl":"https://doi.org/10.1002/mog2.42","url":null,"abstract":"<p>Cuproptosis is a novel form of copper-induced programmed cell death. Here, we investigate the role of cuproptosis-related genes in head and neck squamous cell carcinoma (HNSCC), and the correlations between cuproptosis-related genes and tumor-infiltrating immune cells in the microenvironment. Gene expression data were downloaded from TCGA and analyzed using R. Protein–protein interaction analysis was conducted using STRING and GeneMANIA, while survival analyses examined the correlations between genes and overall survival. In addition, analyses of methylation and mutation sites were performed using Illumina HumanMethylation450 data and the cBioPortal data set, respectively. The correlations between gene expression level and infiltrating immune cells and predictive values of PD-1/PD-L1 blockade responses were also analyzed. Cuproptosis-promoting genes were downregulated, while two out of three cuproptosis-inhibiting genes, GLS and CDKN2A, showed upregulated expression. The CDKN2A expression level was identified as an independent prognostic factor for HNSCC through the multivariate Cox survival analysis. Meanwhile, levels of all cuproptosis-related genes correlated positively with CD4⁺ T cell infiltration. Furthermore, expression of the cuproptosis-promoting gene DLD was negatively correlated with immune score. All cuproptosis-related genes were expressed aberrantly and correlated positively with CD4⁺ T cell infiltration in HNSCC. Thus, copper homeostasis and cuproptosis could be targeted therapeutically as a potential means of enhancing the efficacy of immunotherapy.</p>","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"2 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.42","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50123771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sertindole inhibits autophagic flux and glioma progression","authors":"Baiyang Liu,&nbsp;Yulin Shi,&nbsp;Bo Qin,&nbsp;Dating Cheng,&nbsp;Zhi Nie,&nbsp;Haoqing Zhai,&nbsp;Yao Li,&nbsp;Zhixian Jin,&nbsp;Jun Pu,&nbsp;Dongming Yan,&nbsp;Yongbin Chen,&nbsp;Cuiping Yang","doi":"10.1002/mog2.41","DOIUrl":"https://doi.org/10.1002/mog2.41","url":null,"abstract":"<p>Gliomas, the most lethal brain tumors, often exhibit resistance to conventional chemotherapy and/or radiotherapy. This study reveals that sertindole, a potent dopamine D2 receptor antagonist primarily designed as an antipsychotic medication for schizophrenia, effectively inhibits glioma progression. Our findings demonstrate that sertindole suppresses the proliferation of U251 and U87 tumor cells, impedes cell cycle progression in vitro, and curtails xenograft tumor growth in vivo. Moreover, we present compelling evidence demonstrating the ability of sertindole to enhance the cellular response to the chemotherapeutic agent temozolomide both in vitro and in vivo. Additionally, our findings reveal that sertindole effectively suppresses the self-renewal capacity and expression of stemness-associated genes, such as Nanog and Sox2, in glioma tumor cells and glioma stem cells. A mechanistic investigation demonstrated that sertindole enhances the formation of autophagosome–lysosome complexes while concurrently impeding autophagic flux through the inhibition of lysosomal hydrolytic enzymes CTSD and CTSB, ultimately resulting in decreased growth of tumor cells. In conclusion, our findings suggest that sertindole has the potential to develop into a potent antiglioma therapeutic agent.</p>","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"2 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.41","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50144909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circular RNA circGPRC5A(e2) facilitates gastric cancer progression and metastasis via modulating miR-665/LASP1 and activating PI3K/AKT pathway","authors":"Yixun Lu,&nbsp;Guoxiao Liu,&nbsp;Yanjun Wang,&nbsp;Kai Li,&nbsp;Xinxin Xu,&nbsp;Benlong Zhang,&nbsp;Lin Chen,&nbsp;Hongqing Xi,&nbsp;Xinxin Wang","doi":"10.1002/mog2.39","DOIUrl":"https://doi.org/10.1002/mog2.39","url":null,"abstract":"<p>Gastric cancer (GC) is one of the most commonly diagnosed malignancies worldwide. Compelling evidence indicates that circular RNA (circRNA) played critical roles in multiple cancers. However, the role and mechanisms of circRNAs in GC remains unclear. Here we first identified a notably overexpressed circular RNA hsa_circ_0025506 in GC by human circRNA microarray, designated as circGPRC5A(e2). Next, we found circGPRC5A(e2) was overexpressed in GC cell lines and clinical samples as well. Then, we confirmed that circGPRC5A(e2) was primarily located in the cytoplasm of GC cells and colocation phenomenon was observed with miR-665 via fluorescence in situ hybridization. Functionally, Cell Counting Kit-8, 5-Ethynyl-2′-deoxyuridine, clone formation assay, Transwell invasion assay, wound-healing assay, and animal experiments showed that circGPRC5A(e2) promoted GC proliferation, migration, and invasion in vitro, and tumorigenesis and metastasis in vivo. Mechanistically, we showed that circGPRC5A(e2) could serve as miR-665 sponges and facilitate GC growth and metastasis via modulating miR-665/LIM and SH3 protein 1 (LASP1) axis and activating phosphatidylinositol 3-kinase/AKT pathway. Taken together, this study revealed that circGPRC5A(e2) functioned as an oncogene in GC. The circGPRC5A(e2)/miR-665/LASP1 axis revealed by current research might provide novel biomarkers and promising therapeutic targets for GC.</p>","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"2 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.39","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50138931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Delivering CAR-T cells into solid tumors via hydrogels","authors":"Shun-Yu Wu,&nbsp;Feng Ji,&nbsp;Bin Xu,&nbsp;Fu-Gen Wu","doi":"10.1002/mog2.40","DOIUrl":"https://doi.org/10.1002/mog2.40","url":null,"abstract":"<p>Chimeric antigen receptor (CAR)-T cell therapy is a promising form of cancer immunotherapy that genetically modifies a patient's own T cells to express CARs for the specific recognition and eradication of cancer cells. Unfortunately, unlike the impressive advancements it achieves in hematologic cancer treatment, CAR-T cell therapy has encountered obstacles in treating solid tumors such as high cost, inadequate tumor infiltration, and immunosuppressive tumor microenvironment. Recently, the regional administration of CAR-T cells via hydrogel platforms has been investigated as a potential method to not only promote tumor infiltration, cell expansion, and anticancer efficacy of the CAR-T cells but also provide a multifunctional platform to introduce additional therapeutic agents for achieving potentiated cancer therapy. In this perspective, different design strategies of CAR-T cell delivery hydrogels are introduced. Besides, various types of therapeutic agents incorporated in the hydrogel platforms and diverse hydrogel formulations have been discussed. The current challenges and future research directions on CAR-T cell delivery hydrogels are also proposed. It is hoped that this perspective can help future researchers develop new CAR-T cell delivery hydrogels that can effectively fight against solid tumors.</p>","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"2 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.40","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50138932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lactate: A critical regulator of cell proliferation via anaphase promoting complex remodeling","authors":"Qiqing Yang,&nbsp;Long Zhang,&nbsp;Jun Chen","doi":"10.1002/mog2.38","DOIUrl":"https://doi.org/10.1002/mog2.38","url":null,"abstract":"<p>In a study recently published in <i>Nature</i>, Liu et al. discovered that lactate directly inhibits SUMO-specific peptidase 1 (SENP1), resulting in the stabilization of anaphase promoting complex (APC) subunit 4 (APC4) SUMOylation, and transient binding of APC/cyclosome (APC/C) and ubiquitin conjugating enzyme E2 C (UBE2C), which promotes the ubiquitination and degradation of cyclin B1 and securin.<span>¹</span> Furthermore, sustained accumulation of lactate was found to counteract the effects of anti-mitotic drugs by inducing mitotic slippage, which ultimately facilitates mitotic exit. This study shed light on a potential mechanism behind the observed high levels of lactate in rapidly dividing cells.</p><p>Cancer cells exhibit a unique metabolic phenotype characterized by increased glucose uptake and reliance on aerobic glycolysis to fuel their rapid proliferation. This metabolic shift contributes to lactate accumulation, which is closely associated with cell proliferation; however, the precise mechanism of the latter remains unclear. APC/C is a member of the ubiquitin ligase family that plays a crucial role in regulating the metaphase-to-anaphase transition and mitotic exit by assembling K11-linked ubiquitin chains on substrates such as cyclin B1 and securin.<span>²</span> A recently published work by Liu et al. uncovered a link between lactate and APC/C activity, and elucidated the significance of this connection in cell cycle and cell proliferation modulation.</p><p>To explore the direct effect of elevated lactate levels on the entire proteome, Liu et al. treated native human embryonic kidney cell lysates with 15 or 25 mM <span>l</span>-lactate before conducting thermal proteomic profiling. They observed a significant shift in the thermostability of UBE2C, an E2 enzyme recruited by APC/C upon structural reorganization of its subunits. However, it is unlikely that lactate binds directly to UBE2C because of its low affinity. Moreover, no change in the abundance or posttranslational modification of UBE2C was detected, suggesting that <span>l</span>-lactate might enhance the interaction between UBE2C and APC/C. To verify this hypothesis, cells were first synchronized to pro-metaphase, a period during which APC/C is inhibited due to its interaction with the mitotic checkpoint complex. Subsequently, Liu et al. incubated cell lysates with 15 mM <span>l</span>-lactate and performed immunoprecipitation of APC/C, revealing that <span>l</span>-lactate significantly enhanced the binding between UBE2C and APC/C. In addition, mass spectrometry analysis of APC/C showed a lactate-dependent elevation of SUMO2/3 conjunctions. Previous studies have shown that SUMOylation of APC4 on residues K772 and K798 results in a substantial rearrangement of the WHB domain in APC2, facilitating the binding of UBE2C to APC/C for an efficient APC/C activation.<span>^{3, 4}</span> To further investigate the role of APC4 SUMOylation in lactate-","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"2 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.38","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50121884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gasdermin E plasmid DNA/indocyanine green coloaded hybrid nanoparticles with spatiotemporal controllability to induce pyroptosis for colon cancer treatment","authors":"Ailing Jiang,&nbsp;Mao Wang,&nbsp;Huimin Liu,&nbsp;Simeng Liu,&nbsp;Xiaoshuang Song,&nbsp;Yu Zou,&nbsp;Yuchuan Deng,&nbsp;Qin Qin,&nbsp;Yiran Song,&nbsp;Yu Zheng","doi":"10.1002/mog2.33","DOIUrl":"https://doi.org/10.1002/mog2.33","url":null,"abstract":"<p>Pyroptosis is an immunogenic cell death and would trigger robust antitumor immunity. However, due to cytoxicity of pyroptosis executors, Gasdermin family proteins, it is indispensable to construct tumor-specific vectors. Here, we report the development of a novel vector named lipid-coated poly(lactide-co-glycolide) (PLGA) nanoparticles coloaded with Gasdermin E expressing plasmid DNA (GSDME-pDNA) with a heat-inducible mouse heat shock protein 70 (mHSP70) as the promoter and a photosensitizer indocyanine green (ICG) to activate the mHSP70 element. The cellular internalization and transfection rate of the vector were remarkably enhanced by photothermal treatment. And the mHSP70 promoter further improved the gene transfection rate for about 15-fold. With the combination of oxaliplatin (OXA), the mechanism switch between apoptosis and pyroptosis was fulfilled by cleavage of GSDME through activated caspase-3, which promoted damage-associated molecular patterns (DAMPs) release and increased the infiltration of immune cells at the tumor site. This combination strategy not only prominently inhibited the growth of the treated tumor, but also exhibited a lethal effect on the distal tumors. Besides, mouse colon cancer cell CT26 overexpressing GSDME after OXA treatment had the potential to be the preventive tumor vaccine. This study provides a novel thought and feasible method for the clinical treatment of colon cancer.</p>","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"2 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.33","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50117711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolomic profiling of plasma reveals potential biomarkers for screening and early diagnosis of gastric cancer and precancerous stages","authors":"Lijing Du,&nbsp;Shasha Li,&nbsp;Xue Xiao,&nbsp;Jin Li,&nbsp;Yuanfang Sun,&nbsp;Shuai Ji,&nbsp;Huizi Jin,&nbsp;Zhaolai Hua,&nbsp;Juming Ma,&nbsp;Xi Wang,&nbsp;Shikai Yan","doi":"10.1002/mog2.32","DOIUrl":"https://doi.org/10.1002/mog2.32","url":null,"abstract":"<p>Gastric cancer (GC) faces a great challenge in clinical diagnosis, that it often is detected at advanced stages and there is a loss of optimum time for treatment. Thus, it is necessary to develop effective strategies for diagnosis of GC. In this study, 82 participants were enrolled, including 50 chronic superficial gastritis (CSG) patients, 7 early gastric cancer (EGC), and 25 advanced gastric cancer (AGC) ones. Metabolites profiling on patient plasma was performed. Furthermore, the proposed biomarkers were used to create random forest models, in which discrimination efficiency and accuracy were ascertained by receiver operating characteristic (ROC) curve analysis. <span>l</span>-carnitine, <span>l</span>-proline, pyruvaldehyde, phosphatidylcholines (PC) (14:0/18:0), lysophosphatidylcholine (14:0) (LysoPC 14:0), lysinoalanine were defined as the potential biomarker panel for the diagnosis among CSG and EGC patients. Compared with EGC patients, PC(O-18:0/0:0) and LysoPC(20:4(5Z,8Z,11Z,14Z)) were found to be upregulated in AGC patients, whereas<span>l</span>-proline, <span>l</span>-valine, adrenic acid, and pyruvaldehyde downregulated. Pathway analysis revealed several metabolism disorders, involving amino acids and lipid metabolism. ROC analysis demonstrated a high diagnostic performance in disease diagnosis between CSG and GC. The above results indicate that the biomarker panels are sensitive to early diagnosis of GC disease, which is expected to be a promising diagnostic tool for disease stratification studies.</p>","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"2 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.32","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50142201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune checkpoint inhibitor-related myocarditis in thymic epithelial tumors: Recent progress and perspectives","authors":"Jianqiong Yin,&nbsp;Zhuoran Yao,&nbsp;Jing Pan,&nbsp;Lu Gan,&nbsp;Jianxin Xue","doi":"10.1002/mog2.31","DOIUrl":"https://doi.org/10.1002/mog2.31","url":null,"abstract":"<p>Thymic epithelial tumors (TETs) are rare anterior mediastinal malignancies originating in the thymus with poor outcomes, and standard platinum-based chemotherapy shows limited efficacy for treating metastatic or recurrent disease. In this setting, further improved novel treatment strategies are needed. Immune checkpoint inhibitors (ICIs) are widely applied in clinical practice for cancer therapy and early results of clinical trials have brought notable objective responses and lasting survival benefits to patients with TETs. However, the incidences of immune-related adverse events (irAEs), especially cardiac adverse events, are higher than those of other tumor types. Myocarditis is a rapidly progressive and life-threatening irAE in patients treated with ICIs, thereby hindering the further utilization of ICI in TETs patients. Therefore, this article aims to review the results of case series and clinical trials that evaluated ICIs for the treatment of TETs and to provide an overview of the clinical features of fatal ICI-related myocarditis in TETs. Furthermore, we approach insights into the immunobiology of thymic tumors and focus on revealing the mechanisms of cardiotoxicity in patients with TETs, hoping to provide several valuable insights for maximizing the therapeutic potential of ICIs in TETs.</p>","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"2 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.31","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50136174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A new synthetic lethal strategy expands the application of PARP inhibitors/cisplatin","authors":"Jinrui Wang,&nbsp;Daniel D. Billadeau,&nbsp;Ying Zheng,&nbsp;Da Jia","doi":"10.1002/mog2.28","DOIUrl":"https://doi.org/10.1002/mog2.28","url":null,"abstract":"<p>In a recent study published in <i>Signal Transduction and Targeted Therapy</i>, <i>Zhang</i> et al.<span>¹</span> identified a panel of genes that served as a novel predictor of response to poly adenosine diphosphate-ribose polymerase (PARP) inhibitors/cisplatin in HR proficient patients, which could guide a broader application of PARP inhibitors/cisplatin in cancer therapy.</p><p>Cancer cells differ from normal cells in their ability to repair damaged DNA—most cancer cells lose one or more DNA repair pathways, resulting in greater reliance on the remaining pathways.<span>²</span> Thus, small molecules that can induce DNA damage have been used to treat various cancers. Among them, cisplatin/PARP inhibitors are well established cancer drugs and are used to target tumor cells with homologous recombination (HR) defects.<span>²</span> Platinum salts (carboplatin, cisplatin, and oxaliplatin) are the commonly-used chemotherapeutic agents, which were historically thought to cause cell death by inducing DNA damage.<span>²</span> Recent studies suggest that the mechanisms of action of platinum salts are more diverse<span>³</span> (Figure 1A). Zhang et al.<span>¹</span> further showed that cisplatin promotes cell death through DNA damage-induced ribosomal stress, rather than failed DNA repair, in certain tumor cells. PARP inhibitors are approved for the treatment of ovarian and breast cancers with BRCA1/2 mutations, and act through synthetic lethality in DNA repair-deficient tumors.<span>^3-5</span> However, it is known that some HR-proficient patients also respond well to PARP inhibitors and cisplatin therapy.<span>³</span> Consistently, Zhang et al.<span>¹</span> also identified patients who benefited from the treatment of PARP inhibitors, despite their normal HR functions. Therefore, it is necessary to identify biomarkers that can help to stratify the patients so they will benefit most from PARP inhibitors and cisplatin therapy.</p><p>To identify these biomarkers, the authors analyzed RNA-Seq data from the Cancer Cell Line Encyclopedia and drug sensitivity data (GDSC) from the extensive and Sanger cell line databases<span>¹</span> (Figure 1B). They used weighted gene co-expression network analysis to negatively correlate drug signatures with co-expressed gene modules.<span>¹</span> Through these analyses, the authors found that expression of genes in the ribosome biogenesis pathway could be used to predict cellular drug response to PARP inhibition or cisplatin-based chemotherapy.<span>¹</span> Ultimately, they obtained a panel of 8 genes involved in ribosome biogenesis for further analysis.<span>¹</span></p><p>In the following studies, the authors provided multiple lines of evidence suggesting that these eight genes could be used to predict PARP inhibitors/cisplatin sensitivity.<span>¹</span> First, ","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"2 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.28","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50144503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overexpression of DAPK1 and Beclin1 under oxygen and glucose deprivation conditions promotes excessive autophagy and apoptosis in A549 cells","authors":"Linlin Wu,&nbsp;Wenxue Sun,&nbsp;Dehua Liao,&nbsp;Yujin Guo,&nbsp;Qingying Si,&nbsp;Dadi Xie,&nbsp;Pei Jiang","doi":"10.1002/mog2.30","DOIUrl":"https://doi.org/10.1002/mog2.30","url":null,"abstract":"<p>In this study, we aimed to determine the specific roles of death-associated protein kinase 1 (DAPK1) and Beclin1 in non-small cell lung cancer (NSCLC) under oxygen and glucose deprivation (OGD). We found that OGD caused most cells to shrink, aggregate, and produce many vacuoles in the cytoplasm. Transmission electron microscopy revealed the presence of autophagic vesicles in the OGD group but not in the Control group. Moreover, the cell counting kit-8 assay showed that cell proliferation was reduced in the OGD group. Quantitative reverse transcription-polymerase chain reaction, western blot, and cell function assays showed that DAPK1 overexpression under OGD promoted apoptosis and autophagy in A549 cells. The coimmunoprecipitation assay confirmed the interaction between DAPK1 and Beclin1 protein. Moreover, knockdown of Beclin1 inhibited autophagy, but its overexpression promoted apoptosis in A549 cells. In vivo tumorigenesis experiment revealed that overexpression of DAPK1 promoted A549 cell apoptosis. Collectively, overexpression of DAPK1 and Beclin1 under OGD promoted excessive autophagy and apoptosis in A549 cells. Our study may provide a novel therapeutic target and theoretical basis for NSCLC treatment.</p>","PeriodicalId":100902,"journal":{"name":"MedComm – Oncology","volume":"2 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mog2.30","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50143946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}