Molecular Carcinogenesis最新文献_第10页

Anlotinib induces neuronal-like differentiation of neuroblastoma by downregulating CRMP5. 安罗替尼通过下调CRMP5诱导神经母细胞瘤的神经元样分化

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2024-08-01 Epub Date: 2024-05-23 DOI: 10.1002/mc.23745

Junwen Hu, Wenlong Yang, Kang Wang, Hongyan Xu, Tianxiang Chen, Chao Li, Ting Xiong, Han Xu, Ming Luo, Shouhua Zhang, Jinlong Yan

{"title":"Anlotinib induces neuronal-like differentiation of neuroblastoma by downregulating CRMP5.","authors":"Junwen Hu, Wenlong Yang, Kang Wang, Hongyan Xu, Tianxiang Chen, Chao Li, Ting Xiong, Han Xu, Ming Luo, Shouhua Zhang, Jinlong Yan","doi":"10.1002/mc.23745","DOIUrl":"10.1002/mc.23745","url":null,"abstract":"The therapeutic effect of anlotinib on neuroblastoma is still not fully understood. This study aims to explore the differentiation therapeutic effects of anlotinib on neuroblastoma and its potential association with the neural development regulatory protein collapsin response mediator protein 5 (CRMP5), both in vivo and in vitro. A patient-derived xenograft (PDX) model was established to observe the therapeutic effect of anlotinib. Neuroblastoma cell lines SK-N-SH and SK-N-AS were cultured to observe the morphological impact of anlotinib. Transwell assay was used to evaluate the cell invasion, and Western blot analysis and immunohistochemistry were employed to detect the expressions of neuronal differentiation-related proteins. Results indicate that anlotinib effectively inhibited tumor growth in the PDX model, modulated the expressions of neuronal differentiation markers. In vitro, anlotinib treatment induced neurite outgrowth in neuroblastoma cells and inhibited their invasive ability, reflecting a change in neuronal marker expression patterns consistent with the PDX model. Similarly, in the SK-N-AS mouse xenograft model, anlotinib demonstrated comparable tumor-suppressing effects and promoted neuronal-like differentiation. Additionally, anlotinib significantly downregulated CRMP5 expression in neuroblastoma both in vivo and in vitro. Overexpression of CRMP5 significantly reversed the differentiation therapy effect of anlotinib, exacerbating the aggressiveness and reducing the differentiation level of neuroblastoma. These findings highlight the potential of anlotinib as an anti-neuroblastoma agent. It may suppress tumor proliferation and invasion by promoting the differentiation of tumor cells towards a neuronal-like state, and this differentiation therapy effect involves the inhibition of CRMP5 signaling.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"1559-1571"},"PeriodicalIF":3.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141081287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

IGF2BP2 inhibits invasion and migration of clear cell renal cell carcinoma via targeting Netrin-4 in an m⁶A-dependent manner. IGF2BP2 以 m6A 依赖性方式通过靶向 Netrin-4 抑制透明细胞肾细胞癌的侵袭和迁移。

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2024-08-01 Epub Date: 2024-05-23 DOI: 10.1002/mc.23746

Gui Wang, Tao Zhuang, Fei Zhen, Chu Zhang, Qichao Wang, Xu Miao, Nienie Qi, Ruiqin Yao

{"title":"IGF2BP2 inhibits invasion and migration of clear cell renal cell carcinoma via targeting Netrin-4 in an m6A-dependent manner.","authors":"Gui Wang, Tao Zhuang, Fei Zhen, Chu Zhang, Qichao Wang, Xu Miao, Nienie Qi, Ruiqin Yao","doi":"10.1002/mc.23746","DOIUrl":"10.1002/mc.23746","url":null,"abstract":"Clear cell renal cell carcinoma (ccRCC), the most common subtype of renal cell carcinoma, often leads to a poor prognosis due to metastasis. The investigation of N6-methyladenosine (m6A) methylation, a crucial RNA modification, and its role in ccRCC, particularly through the m6A reader insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2), revealed significant insights. We found that IGF2BP2 was notably downregulated in ccRCC, which correlated with tumor aggressiveness and poor prognosis. Thus, IGFBP2 has emerged as an independent prognostic factor of ccRCC. Moreover, a strong positive correlation was observed between the expression of IGF2BP2 and Netrin-4. Netrin-4 was also downregulated in ccRCC, and its lower levels were associated with increased malignancy and poor prognosis. Overexpression of IGF2BP2 and Netrin-4 suppressed the invasion and migration of ccRCC cells, while Netrin-4 knockdown reversed these effects in ccRCC cell lines. RNA immunoprecipitation (RIP)-quantitative polymerase chain reaction validated the robust enrichment of Netrin-4 mRNA in anti-IGF2BP2 antibody immunoprecipitates. MeRlP showed significantly increased Netrin4 m6A levels after lGF2BP2 overexpression. Moreover, we found that IGF2BP2 recognized and bound to the m6A site within the coding sequence of Netrin-4, enhancing its mRNA stability. Collectively, these results showed that IGF2BP2 plays a suppressive role in the invasion and migration of ccRCC cells by targeting Netrin-4 in an m6A-dependent manner. These findings underscore the potential of IGF2BP2/Netrin-4 as a promising prognostic biomarker and therapeutic target in patients with ccRCC metastasis.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"1572-1587"},"PeriodicalIF":3.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141081327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

LDHA-mediated M2-type macrophage polarization via tumor-derived exosomal EPHA2 promotes renal cell carcinoma progression. LDHA通过肿瘤外泌体EPHA2介导的M2型巨噬细胞极化促进了肾细胞癌的进展。

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2024-08-01 Epub Date: 2024-05-23 DOI: 10.1002/mc.23737

Xinxin Gan, Jiatao Hu, Qingyang Pang, Rui Yan, Yi Bao, Ying Liu, Jiaao Song, Zheng Wang, Weihao Sun, Fuzhao Huang, Chen Cai, Linhui Wang

{"title":"LDHA-mediated M2-type macrophage polarization via tumor-derived exosomal EPHA2 promotes renal cell carcinoma progression.","authors":"Xinxin Gan, Jiatao Hu, Qingyang Pang, Rui Yan, Yi Bao, Ying Liu, Jiaao Song, Zheng Wang, Weihao Sun, Fuzhao Huang, Chen Cai, Linhui Wang","doi":"10.1002/mc.23737","DOIUrl":"10.1002/mc.23737","url":null,"abstract":"Lactate dehydrogenase A (LDHA) is known to promote the growth and invasion of various types of tumors, affects tumor resistance, and is associated with tumor immune escape. But how LDHA reshapes the tumor microenvironment and promotes the progression of renal cell carcinoma (RCC) remains unclear. In this study, we found that LDHA was highly expressed in clear cell RCC (ccRCC), and this high expression was associated with macrophage infiltration, while macrophages were highly infiltrated in ccRCC, affecting patient prognosis via M2-type polarization. Our in vivo and in vitro experiments demonstrated that LDHA and M2-type macrophages could enhance the proliferation, invasion, and migration abilities of ccRCC cells. Mechanistically, high expression of LDHA in ccRCC cells upregulated the expression of EPHA2 in exosomes derived from renal cancer. Exosomal EPHA2 promoted M2-type polarization of macrophages by promoting activation of the PI3K/AKT/mTOR pathway in macrophages, thereby promoting the progression of ccRCC. All these findings suggest that EPHA2 may prove to be a potential therapeutic target for advanced RCC.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"1486-1499"},"PeriodicalIF":3.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141081334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Curcuminoid PBPD induces cuproptosis and endoplasmic reticulum stress in cervical cancer via the Notch1/RBP-J/NRF2/FDX1 pathway. 姜黄素PBPD通过Notch1/RBP-J/NRF2/FDX1途径诱导宫颈癌的杯突症和内质网应激反应

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2024-08-01 Epub Date: 2024-05-27 DOI: 10.1002/mc.23735

Min-Jie Zhang, Mengna Shi, Yang Yu, Rongying Ou, Ren-Shan Ge, Ping Duan

{"title":"Curcuminoid PBPD induces cuproptosis and endoplasmic reticulum stress in cervical cancer via the Notch1/RBP-J/NRF2/FDX1 pathway.","authors":"Min-Jie Zhang, Mengna Shi, Yang Yu, Rongying Ou, Ren-Shan Ge, Ping Duan","doi":"10.1002/mc.23735","DOIUrl":"10.1002/mc.23735","url":null,"abstract":"Curcumin has been shown to have antitumor properties, but its low potency and bioavailability has limited its clinical application. We designed a novel curcuminoid, [1-propyl-3,5-bis(2-bromobenzylidene)-4-piperidinone] (PBPD), which has higher antitumor strength and improves bioavailability. Cell counting kit-8 was used to detect cell activity. Transwell assay was used to detect cell invasion and migration ability. Western blot and quantitative polymerase chain reaction were used to detect protein levels and their messenger RNA expression. Immunofluorescence was used to detect the protein location. PBPD significantly inhibited the proliferation of cervical cancer cells, with an IC50 value of 4.16 μM for Hela cells and 3.78 μM for SiHa cells, leading to the induction of cuproptosis. Transcriptome sequencing analysis revealed that PBPD significantly inhibited the Notch1/Recombination Signal Binding Protein for Immunoglobulin kappa J Region (RBP-J) and nuclear factor erythroid 2-related factor 2 (NRF2) signaling pathways while upregulating ferredoxin 1 (FDX1) expression. Knockdown of Notch1 or RBP-J significantly inhibited NRF2 expression and upregulated FDX1 expression, leading to the inhibition of nicotinamide adenine dinucleotide phosphate activity and the induction of oxidative stress, which in turn activated endoplasmic reticulum stress and induced cell death. The overexpression of Notch1 or RBP-J resulted in the enrichment of RBP-J within the NRF2 promoter region, thereby stimulating NRF2 transcription. NRF2 knockdown resulted in increase in FDX1 expression, leading to cuproptosis. In addition, PBPD inhibited the acidification of tumor niche and reduced cell metabolism to inhibit cervical cancer cell invasion and migration. In conclusion, PBPD significantly inhibits the proliferation, invasion, and migration of cervical cancer cells and may be a novel potential drug candidate for treatment of cervical cancer.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"1449-1466"},"PeriodicalIF":3.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141154297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

KNTC1 knockdown inhibits the proliferation and migration of osteosarcoma cells by MCM2. 敲除 KNTC1 可通过 MCM2 抑制骨肉瘤细胞的增殖和迁移。

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2024-08-01 Epub Date: 2024-05-31 DOI: 10.1002/mc.23748

Lei Zhong, Yuanwei Dong, Shuqin Liu

{"title":"KNTC1 knockdown inhibits the proliferation and migration of osteosarcoma cells by MCM2.","authors":"Lei Zhong, Yuanwei Dong, Shuqin Liu","doi":"10.1002/mc.23748","DOIUrl":"10.1002/mc.23748","url":null,"abstract":"Osteosarcoma (OS) is a common primary malignant bone tumor, and it is necessary to further investigate the molecular mechanism of OS progression. The expression of kinetochore associated protein 1 (KNTC1) and minichromosome maintenance 2 (MCM2) was detected by immunohistochemistry, quantitative PCR (qPCR) and Western blot. Gene knockdown or overexpression cell models were constructed and the proliferation, apoptosis, cell cycle and migration were detected in vitro, besides, xenograft models were established to explore the effects of KNTC1 downregulation in vivo. Public databased and bioinformatics analysis were performed to screen the downstream molecules and determine the expression of MCM2 in cancers. KNTC1 was overexpressed in OS tissues and positively correlated with overall survival of OS patients. KNTC1 knockdown inhibited the proliferation and migration, and arrested G2 phase, and induced apoptosis. Besides, KNTC1 downregulation restricted the xenograft tumor formation. MCM2, one of the coexpressed genes, was highly expressed in sarcoma and downregulated after KNTC1 knockdown. MCM2 overexpression heightened the proliferation and migration ability of OS cells, which was reversed the inhibiting effects of KNTC1 knockdown. KNTC1 was overexpressed in OS and promoted the progression of OS by upregulating MCM2.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"1599-1610"},"PeriodicalIF":3.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141179613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Multifaceted roles of PD-1 in tumorigenesis: From immune checkpoint to tumor cell-intrinsic function. PD-1 在肿瘤发生中的多重作用：从免疫检查点到肿瘤细胞内在功能

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2024-08-01 Epub Date: 2024-05-15 DOI: 10.1002/mc.23740

Huiqing Chen, Jiayu Wei, Zhen Zhu, Yongzhong Hou

引用次数: 0

RETRACTION: "LncAPC Drives Wnt/Β-Catenin Activation and Liver TIC Self-Renewal Through EZH2 Mediated APC Transcriptional Inhibition". 返回：《LncAPC 通过 EZH2 介导的 APC 转录抑制驱动 Wnt/Β-Catenin 激活和肝脏 TIC 自我更新》。

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2024-08-01 Epub Date: 2024-06-19 DOI: 10.1002/mc.23780

引用次数: 0

The serine protease CORIN promotes progression of gastric cancer by mediating the ERK1/2 MAPK pathway. 丝氨酸蛋白酶 CORIN 通过介导 ERK1/2 MAPK 通路促进胃癌的进展。

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2024-08-01 Epub Date: 2024-05-15 DOI: 10.1002/mc.23739

Runqi Hong, Xiaotian Zhang, Yi Zhang, Lanxin Bei, Ju Yang, Jie Xia, Zhiqing Hu, Zhipeng Cao, Rui Chen, Liang Chen, Gengming Niu, Chongwei Ke

{"title":"The serine protease CORIN promotes progression of gastric cancer by mediating the ERK1/2 MAPK pathway.","authors":"Runqi Hong, Xiaotian Zhang, Yi Zhang, Lanxin Bei, Ju Yang, Jie Xia, Zhiqing Hu, Zhipeng Cao, Rui Chen, Liang Chen, Gengming Niu, Chongwei Ke","doi":"10.1002/mc.23739","DOIUrl":"10.1002/mc.23739","url":null,"abstract":"The serine protease CORIN catalyzes pro-atrial natriuretic peptide (pro-ANP) into an active ANP and maintains homeostasis of the internal environment. However, it is unclear whether CORIN participates in the regulation of tumor progression. We analyzed the expression profile of CORIN in gastric cancer tissues (GCs) and adjacent nontumoral tissues (NTs). We investigated the prognostic value of CORIN in GC patients. We characterized the in vitro and in vivo activity of CORIN in cultured GC cells with gain-of-function and loss-of-function experiments. The underlying mechanism was explored by using bioinformatics, a signaling antibody array, and confirmative western blot analyses, as well as rescue experiments with highly selective small-molecule inhibitors targeting the ERK1/2 MAPK signaling pathway. CORIN was upregulated in GCs than in NTs. Overexpression of CORIN was correlated with unfavorable prognoses in patients with GC. Ectopic expression of CORIN was promoted, whereas silencing of CORIN suppressed proliferation, colony formation, migration and invasion of GC cells, and tumor growth in vivo. Overexpression of CORIN-induced epithelial-mesenchymal transition (EMT) and activation of the ERK1/2 MAPK signaling pathway, while silencing of CORIN yielded opposite results. The in vitro tumor-promoting potency of CORIN could be antagonized by selective inhibitors targeting the ERK1/2 MAPK pathway. In conclusion, CORIN is a potential prognostic marker and therapeutic target for GC patients, which may promote tumor progression by mediating the ERK1/2 MAPK signaling pathway and EMT in GC cells.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"1500-1514"},"PeriodicalIF":3.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140945626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

HER3 V104 mutations regulate cell signaling, growth, and drug sensitivity in cancer. HER3 V104 突变调节癌症的细胞信号、生长和药物敏感性。

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2024-08-01 Epub Date: 2024-05-15 DOI: 10.1002/mc.23743

Rosalin Mishra, Mary Kate Kilroy, Wasim Feroz, Hima Patel, Joan T Garrett

{"title":"HER3 V104 mutations regulate cell signaling, growth, and drug sensitivity in cancer.","authors":"Rosalin Mishra, Mary Kate Kilroy, Wasim Feroz, Hima Patel, Joan T Garrett","doi":"10.1002/mc.23743","DOIUrl":"10.1002/mc.23743","url":null,"abstract":"HER3 is mutated in ~2%-10% of cancers depending on the cancer type. We found the HER3-V104L mutation to be activating from patient-derived mutations introduced via lentiviral transduction in HER3KO HER2 + HCC1569 breast cancer cells in which endogenous HER3 was eliminated by CRISPR/Cas9. Cells expressing HER3-V104L showed higher p-HER3 and p-ERK1/2 expression versus cells expressing wild-type HER3 or HER3-V104M. Patients whose tumor expressed the HER3 V104L variant had a reduced probability of overall survival compared to patients lacking a HER3 mutation whereas we did not find a statistically significant difference in overall survival of various cancer patients with the HER3 V104M mutation. Our data showed that HER2 inhibitors suppressed cell growth of HCC1569HER3KO cells stably expressing the HER3-V104L mutation. Cancer cell lines (SNU407, UC15 and DV90) with endogenous HER3-V104M mutation showed reduced cell proliferation and p-HER2/p-ERK1/2 expression with HER2 inhibitor treatment. Knock down of HER3 abrogated cell proliferation in the above cell lines which were overall more sensitive to the ERK inhibitor SCH779284 versus PI3K inhibitors. HER3-V104L mutation stabilized HER3 protein expression in COS7 and SNUC5 cells. COS7 cells transiently transfected with the HER3-V104L mutation in the presence of HER binding partners showed higher expression of p-HER3, p-ERK1/2 versus HER3-WT in a NRG-independent manner without any change in AKT signaling. Overall, this study shows the clinical relevance of the HER3 V104L and the V104M mutations and its response to HER2, PI3K and ERK inhibitors.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"1528-1541"},"PeriodicalIF":3.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140945599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Atypical BCR-ABL1 transcript in mixed phenotype acute leukemia with bone marrow necrosis. 混合表型急性白血病伴骨髓坏死的非典型 BCR-ABL1 转录本。

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2024-08-01 Epub Date: 2024-06-11 DOI: 10.1002/mc.23742

Jiarui Liu, Yujie Jiang, Dai Yuan, Zhifen Zhang, Xin Liu, Wenbo Zhao, Hongzhi Xu

引用次数: 0