Molecular biomedicine最新文献_第9页

UCHL5 is a putative prognostic marker in renal cell carcinoma: a study of UCHL family. UCHL5 是肾细胞癌的潜在预后标志物：对 UCHL 家族的研究。

IF 6.3

Molecular biomedicine Pub Date : 2024-07-22 DOI: 10.1186/s43556-024-00192-0

Mengdi Zhang, Jingxian Li, Sijia Liu, Fangfang Zhou, Long Zhang

{"title":"UCHL5 is a putative prognostic marker in renal cell carcinoma: a study of UCHL family.","authors":"Mengdi Zhang, Jingxian Li, Sijia Liu, Fangfang Zhou, Long Zhang","doi":"10.1186/s43556-024-00192-0","DOIUrl":"10.1186/s43556-024-00192-0","url":null,"abstract":"A macroscopic perspective is indispensable for understanding the intricate relationship between deubiquitinases and tumorigenesis. Proteomics has been proposed as a viable approach for elucidating the complex role of deubiquitylation in cellular progression. Instead of studying the function of a single ubiquitinase, research on a deubiquitinase family with similar catalytic core(s) may provide a new perspective for the pathological understanding of cancer. The Ubiquitin C-terminal hydrolase L (UCHL) family consists of four members: UCHL1, UCHL3, UCHL5, and BRAC1 associated protein-1 (BAP1), and they have been implicated in tumorigenesis and metastasis. Some members are considered hallmarks of intracranial lesions, colon cancer, chromatin remodeling, and histone stability. The present study uncovered an unknown correlation between the UCHL family and renal cancer. We discovered that UCHLs exhibit diverse regulatory effects in renal cancer, establishing connections between the renal cancer and truncated gene mutations, mitochondrial energetic metastasis, immune cell infiltration, and chromosomal stability of UCHLs family. Notably, we found that the increase of UCHL5 expression in renal cancer cells decreases the antigen processing and presentation of RCC tumor-infiltrating B cells. Further research identified that the expression of UCHL5 in RCC tumors is correlated with transport proteins, which led us to find that the abundance of UCHL5 in the blood of late-stage renal cell cancer patients is upregulated from 18 ng/L to 500 ng/L. Therefore, we propose that the abundance of UCHL5 in patients' blood can be a possible indicator of poor prognosis for renal cell cancer.","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"28"},"PeriodicalIF":6.3,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11265068/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141735854","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}

引用次数: 0

m6A-dependent mature miR-151-5p accelerates the malignant process of HNSCC by targeting LYPD3. 依赖于 m6A 的成熟 miR-151-5p 通过靶向 LYPD3 加速了 HNSCC 的恶性进程。

IF 6.3

Molecular biomedicine Pub Date : 2024-07-16 DOI: 10.1186/s43556-024-00189-9

Fei Huang, Yuan Ren, Yufei Hua, Ying Wang, Ruomeng Li, Ning Ji, Xin Zeng, Ding Bai, Qianming Chen, Xikun Zhou, Junjie Wu, Jing Li

{"title":"m6A-dependent mature miR-151-5p accelerates the malignant process of HNSCC by targeting LYPD3.","authors":"Fei Huang, Yuan Ren, Yufei Hua, Ying Wang, Ruomeng Li, Ning Ji, Xin Zeng, Ding Bai, Qianming Chen, Xikun Zhou, Junjie Wu, Jing Li","doi":"10.1186/s43556-024-00189-9","DOIUrl":"10.1186/s43556-024-00189-9","url":null,"abstract":"miRNA has emerged as a crucial regulator in various of pathological and physiological processes, yet its precise mechanism of action the detailed mechanism of their action in Head and neck squamous cell carcinoma (HNSCC) remains incompletely understood. This study sheds light on the role of mi-151-5p, revealing its significantly elevated expression in tumor cells, which notably enhances the invasion and migration of HNSCC cells. This effect is achieved through directly targeting LY6/PLAUR Domain Containing 3 (LYPD3) by miR-151-5p, involving complementary binding to the 3'-untranslated regions (3'-UTR) in the mRNA of LYPD3. Consequently, this interaction accelerates the metastasis of HNSCC. Notably, clinical observations indicate a correlation between high expression of miR-151-5p and low levels of LYPD3 in clinical settings are correlated with poor prognosis of HNSCC patients. Furthermore, our investigation demonstrates that glycosylation of LYPD3 modulates its subcellular localization and reinforces its role in suppressing HNSCC metastasis. Additionally, we uncover a potential regulatory mechanism involving the facilitation of miR-151-5p maturation and accumulation through N6-methyladenosine (m6A) modification. This process is orchestrated by methyltransferase-like 3 (METTL3) and mediated by a newly identified reader, heterogeneous nuclear ribonucleoprotein U (hnRNP U). These findings collectively underscore the significance of the METTL3/miR-151-5p/LYPD3 axis serves as a prominent driver in the malignant progression of HNSCC.","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"27"},"PeriodicalIF":6.3,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11250566/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141621881","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}

引用次数: 0

Exploring haematopoietic stem cell dynamics through mitochondrial mutation profiling. 通过线粒体突变特征分析探索造血干细胞的动态变化。

IF 6.3

Molecular biomedicine Pub Date : 2024-07-10 DOI: 10.1186/s43556-024-00190-2

Yongming Xia, Ruixiu Chen, Shiwei Duan

引用次数: 0

Multiple myeloma: signaling pathways and targeted therapy. 多发性骨髓瘤：信号通路和靶向治疗。

IF 6.3

Molecular biomedicine Pub Date : 2024-07-04 DOI: 10.1186/s43556-024-00188-w

Qizhong Lu, Donghui Yang, Hexian Li, Ting Niu, Aiping Tong

{"title":"Multiple myeloma: signaling pathways and targeted therapy.","authors":"Qizhong Lu, Donghui Yang, Hexian Li, Ting Niu, Aiping Tong","doi":"10.1186/s43556-024-00188-w","DOIUrl":"10.1186/s43556-024-00188-w","url":null,"abstract":"Multiple myeloma (MM) is the second most common hematological malignancy of plasma cells, characterized by osteolytic bone lesions, anemia, hypercalcemia, renal failure, and the accumulation of malignant plasma cells. The pathogenesis of MM involves the interaction between MM cells and the bone marrow microenvironment through soluble cytokines and cell adhesion molecules, which activate various signaling pathways such as PI3K/AKT/mTOR, RAS/MAPK, JAK/STAT, Wnt/β-catenin, and NF-κB pathways. Aberrant activation of these pathways contributes to the proliferation, survival, migration, and drug resistance of myeloma cells, making them attractive targets for therapeutic intervention. Currently, approved drugs targeting these signaling pathways in MM are limited, with many inhibitors and inducers still in preclinical or clinical research stages. Therapeutic options for MM include non-targeted drugs like alkylating agents, corticosteroids, immunomodulatory drugs, proteasome inhibitors, and histone deacetylase inhibitors. Additionally, targeted drugs such as monoclonal antibodies, chimeric antigen receptor T cells, bispecific T-cell engagers, and bispecific antibodies are being used in MM treatment. Despite significant advancements in MM treatment, the disease remains incurable, emphasizing the need for the development of novel or combined targeted therapies based on emerging theoretical knowledge, technologies, and platforms. In this review, we highlight the key role of signaling pathways in the malignant progression and treatment of MM, exploring advances in targeted therapy and potential treatments to offer further insights for improving MM management and outcomes.","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"25"},"PeriodicalIF":6.3,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11222366/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141499754","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}

引用次数: 0

Single-cell transcriptomic profiling reveals decreased ER protein Reticulon3 drives the progression of renal fibrosis. 单细胞转录组分析显示，ER 蛋白 Reticulon3 的减少推动了肾脏纤维化的进展。

IF 6.3

Molecular biomedicine Pub Date : 2024-06-28 DOI: 10.1186/s43556-024-00187-x

Shuai Guo, Yi Dong, Ran Du, Yu-Xing Liu, Shu Liu, Qin Wang, Ji-Shi Liu, Hui Xu, Yu-Jie Jiang, Huang Hao, Liang-Liang Fan, Rong Xiang

{"title":"Single-cell transcriptomic profiling reveals decreased ER protein Reticulon3 drives the progression of renal fibrosis.","authors":"Shuai Guo, Yi Dong, Ran Du, Yu-Xing Liu, Shu Liu, Qin Wang, Ji-Shi Liu, Hui Xu, Yu-Jie Jiang, Huang Hao, Liang-Liang Fan, Rong Xiang","doi":"10.1186/s43556-024-00187-x","DOIUrl":"10.1186/s43556-024-00187-x","url":null,"abstract":"Chronic kidney disease (CKD) poses a significant global health dilemma, emerging from complex causes. Although our prior research has indicated that a deficiency in Reticulon-3 (RTN3) accelerates renal disease progression, a thorough examination of RTN3 on kidney function and pathology remains underexplored. To address this critical need, we generated Rtn3-null mice to study the consequences of RTN3 protein deficiency on CKD. Single-cell transcriptomic analyses were performed on 47,885 cells from the renal cortex of both healthy and Rtn3-null mice, enabling us to compare spatial architectures and expression profiles across 14 distinct cell types. Our analysis revealed that RTN3 deficiency leads to significant alterations in the spatial organization and gene expression profiles of renal cells, reflecting CKD pathology. Specifically, RTN3 deficiency was associated with Lars2 overexpression, which in turn caused mitochondrial dysfunction and increased reactive oxygen species levels. This shift induced a transition in renal epithelial cells from a functional state to a fibrogenic state, thus promoting renal fibrosis. Additionally, RTN3 deficiency was found to drive the endothelial-to-mesenchymal transition process and disrupt cell-cell communication, further exacerbating renal fibrosis. Immunohistochemistry and Western-Blot techniques were used to validate these observations, reinforcing the critical role of RTN3 in CKD pathogenesis. The deficiency of RTN3 protein in CKD leads to profound changes in cellular architecture and molecular profiles. Our work seeks to elevate the understanding of RTN3's role in CKD's narrative and position it as a promising therapeutic contender.","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"24"},"PeriodicalIF":6.3,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11211315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141473295","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}

引用次数: 0

Inhibition of cysteine-serine-rich nuclear protein 1 ameliorates ischemia-reperfusion injury during liver transplantation in an MAPK-dependent manner. 抑制富含半胱氨酸-丝氨酸的核蛋白 1 能以 MAPK 依赖性方式改善肝移植过程中的缺血再灌注损伤。

IF 6.3

Molecular biomedicine Pub Date : 2024-06-21 DOI: 10.1186/s43556-024-00185-z

Zhoucheng Wang, Wenwen Ge, Xinyang Zhong, Shizheng Tong, Shusen Zheng, Xiao Xu, Kai Wang

{"title":"Inhibition of cysteine-serine-rich nuclear protein 1 ameliorates ischemia-reperfusion injury during liver transplantation in an MAPK-dependent manner.","authors":"Zhoucheng Wang, Wenwen Ge, Xinyang Zhong, Shizheng Tong, Shusen Zheng, Xiao Xu, Kai Wang","doi":"10.1186/s43556-024-00185-z","DOIUrl":"10.1186/s43556-024-00185-z","url":null,"abstract":"Hepatic ischemia-reperfusion injury (HIRI) is a critical pathophysiological process during liver transplantation (LT). Multiple genes and signal pathways are dysregulated during HIRI. This study aims to identify genes as potential therapeutic targets for ameliorating HIRI. Datasets containing samples from the human donor liver (GSE151648) and mouse HIRI model (GSE117066) were analyzed to determine differentially expressed genes (DEGs). The selected DEGs were confirmed by real-time PCR and western blot in the hepatocyte hypoxia-reoxygenation (HR) model, mouse HIRI model, and human liver samples after transplantation. Genetic inhibition was used to further clarify the underlying mechanism of the gene in vitro and in vivo. Among the DEGs, CSRNP1 was significantly upregulated (|log FC|= 2.08, P < 0.001), and was positively correlated with the MAPK signal pathway (R = 0.67, P < 0.001). CSRNP1 inhibition by siRNA significantly suppressed apoptosis in the AML-12 cell line after HR (mean Annexin+ ratio = 60.62% vs 42.47%, P = 0.0019), but the protective effect was eliminated with an additional MAPK activator. Knocking down CSRNP1 gene expression by intravenous injection of AAV-shRNA markedly reduced liver injury in mouse HIRI model (ALT: AAV-NC vs AAV-shCsrnp1 = 26,673.5 ± 2761.2 vs 3839.7 ± 1432.8, P < 0.001; AST: AAV-NC vs AAV-shCsrnp1 = 8640.5 ± 1450.3 vs 1786.8 ± 518.3, P < 0.001). Liver-targeted delivery of siRNA by nanoparticles effectively inhibited intra-hepatic genetic expression of Csrnp1 and alleviated IRI by reducing tissue inflammation and hepatocyte apoptosis. Furthermore, CSRNP1 inhibition was associated with reduced activation of the MAPK pathway both in vitro and in vivo. In conclusion, our results demonstrated that CSRNP1 could be a potential therapeutic target to ameliorate HIRI in an MAPK-dependent manner.","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"22"},"PeriodicalIF":6.3,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11189853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141433533","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}

引用次数: 0

Ckip-1 3'UTR alleviates prolonged sleep deprivation induced cardiac dysfunction by activating CaMKK2/AMPK/cTNI pathway. Ckip-1 3'UTR通过激活CaMKK2/AMPK/cTNI通路缓解长期睡眠剥夺诱发的心功能障碍。

IF 6.3

Molecular biomedicine Pub Date : 2024-06-14 DOI: 10.1186/s43556-024-00186-y

Beilei Dong, Rui Xue, Jianwei Li, Shukuan Ling, Wenjuan Xing, Zizhong Liu, Xinxin Yuan, Junjie Pan, Ruikai Du, Xinming Shen, Jingwen Zhang, Youzhi Zhang, Yingxian Li, Guohui Zhong

{"title":"Ckip-1 3'UTR alleviates prolonged sleep deprivation induced cardiac dysfunction by activating CaMKK2/AMPK/cTNI pathway.","authors":"Beilei Dong, Rui Xue, Jianwei Li, Shukuan Ling, Wenjuan Xing, Zizhong Liu, Xinxin Yuan, Junjie Pan, Ruikai Du, Xinming Shen, Jingwen Zhang, Youzhi Zhang, Yingxian Li, Guohui Zhong","doi":"10.1186/s43556-024-00186-y","DOIUrl":"10.1186/s43556-024-00186-y","url":null,"abstract":"Sleep deprivation (SD) has emerged as a critical concern impacting human health, leading to significant damage to the cardiovascular system. However, the underlying mechanisms are still unclear, and the development of targeted drugs is lagging. Here, we used mice to explore the effects of prolonged SD on cardiac structure and function. Echocardiography analysis revealed that cardiac function was significantly decreased in mice after five weeks of SD. Real-time quantitative PCR (RT-q-PCR) and Masson staining analysis showed that cardiac remodeling marker gene Anp (atrial natriuretic peptide) and fibrosis were increased, Elisa assay of serum showed that the levels of creatine kinase (CK), creatine kinase-MB (CK-MB), ANP, brain natriuretic peptide (BNP) and cardiac troponin T (cTn-T) were increased after SD, suggesting that cardiac remodeling and injury occurred. Transcript sequencing analysis indicated that genes involved in the regulation of calcium signaling pathway, dilated cardiomyopathy, and cardiac muscle contraction were changed after SD. Accordingly, Western blotting analysis demonstrated that the cardiac-contraction associated CaMKK2/AMPK/cTNI pathway was inhibited. Since our preliminary research has confirmed the vital role of Casein Kinase-2 -Interacting Protein-1 (CKIP-1, also known as PLEKHO1) in cardiac remodeling regulation. Here, we found the levels of the 3' untranslated region of Ckip-1 (Ckip-1 3'UTR) decreased, while the coding sequence of Ckip-1 (Ckip-1 CDS) remained unchanged after SD. Significantly, adenovirus-mediated overexpression of Ckip-1 3'UTR alleviated SD-induced cardiac dysfunction and remodeling by activating CaMKK2/AMPK/cTNI pathway, which proposed the therapeutic potential of Ckip-1 3'UTR in treating SD-induced heart disease.","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"23"},"PeriodicalIF":6.3,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11176284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141319180","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}

引用次数: 0

Signaling pathways in colorectal cancer implications for the target therapies. 结直肠癌信号通路对靶向疗法的影响。

IF 6.3

Molecular biomedicine Pub Date : 2024-06-07 DOI: 10.1186/s43556-024-00178-y

Yanlin Song, Ming Chen, Yuhao Wei, Xuelei Ma, Huashan Shi

{"title":"Signaling pathways in colorectal cancer implications for the target therapies.","authors":"Yanlin Song, Ming Chen, Yuhao Wei, Xuelei Ma, Huashan Shi","doi":"10.1186/s43556-024-00178-y","DOIUrl":"10.1186/s43556-024-00178-y","url":null,"abstract":"Colorectal carcinoma (CRC) stands as a pressing global health issue, marked by the unbridled proliferation of immature cells influenced by multifaceted internal and external factors. Numerous studies have explored the intricate mechanisms of tumorigenesis in CRC, with a primary emphasis on signaling pathways, particularly those associated with growth factors and chemokines. However, the sheer diversity of molecular targets introduces complexity into the selection of targeted therapies, posing a significant challenge in achieving treatment precision. The quest for an effective CRC treatment is further complicated by the absence of pathological insights into the mutations or alterations occurring in tumor cells. This study reveals the transfer of signaling from the cell membrane to the nucleus, unveiling recent advancements in this crucial cellular process. By shedding light on this novel dimension, the research enhances our understanding of the molecular intricacies underlying CRC, providing a potential avenue for breakthroughs in targeted therapeutic strategies. In addition, the study comprehensively outlines the potential immune responses incited by the aberrant activation of signaling pathways, with a specific focus on immune cells, cytokines, and their collective impact on the dynamic landscape of drug development. This research not only contributes significantly to advancing CRC treatment and molecular medicine but also lays the groundwork for future breakthroughs and clinical trials, fostering optimism for improved outcomes and refined approaches in combating colorectal carcinoma.","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"21"},"PeriodicalIF":6.3,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11156834/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141285576","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}

引用次数: 0

Signaling pathways in liver cancer: pathogenesis and targeted therapy. 肝癌的信号通路：发病机制和靶向治疗。

IF 6.3

Molecular biomedicine Pub Date : 2024-05-31 DOI: 10.1186/s43556-024-00184-0

Yangtao Xue, Yeling Ruan, Yali Wang, Peng Xiao, Junjie Xu

{"title":"Signaling pathways in liver cancer: pathogenesis and targeted therapy.","authors":"Yangtao Xue, Yeling Ruan, Yali Wang, Peng Xiao, Junjie Xu","doi":"10.1186/s43556-024-00184-0","DOIUrl":"10.1186/s43556-024-00184-0","url":null,"abstract":"Liver cancer remains one of the most prevalent malignancies worldwide with high incidence and mortality rates. Due to its subtle onset, liver cancer is commonly diagnosed at a late stage when surgical interventions are no longer feasible. This situation highlights the critical role of systemic treatments, including targeted therapies, in bettering patient outcomes. Despite numerous studies on the mechanisms underlying liver cancer, tyrosine kinase inhibitors (TKIs) are the only widely used clinical inhibitors, represented by sorafenib, whose clinical application is greatly limited by the phenomenon of drug resistance. Here we show an in-depth discussion of the signaling pathways frequently implicated in liver cancer pathogenesis and the inhibitors targeting these pathways under investigation or already in use in the management of advanced liver cancer. We elucidate the oncogenic roles of these pathways in liver cancer especially hepatocellular carcinoma (HCC), as well as the current state of research on inhibitors respectively. Given that TKIs represent the sole class of targeted therapeutics for liver cancer employed in clinical practice, we have particularly focused on TKIs and the mechanisms of the commonly encountered phenomena of its resistance during HCC treatment. This necessitates the imperative development of innovative targeted strategies and the urgency of overcoming the existing limitations. This review endeavors to shed light on the utilization of targeted therapy in advanced liver cancer, with a vision to improve the unsatisfactory prognostic outlook for those patients.","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"20"},"PeriodicalIF":6.3,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11139849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141180772","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}

引用次数: 0

Carcinoembryonic antigen potentiates non-small cell lung cancer progression via PKA-PGC-1ɑ axis. 癌胚抗原通过 PKA-PGC-1ɑ 轴促进非小细胞肺癌的进展

IF 6.3

Molecular biomedicine Pub Date : 2024-05-24 DOI: 10.1186/s43556-024-00181-3

Juan Lei, Lei Wu, Nan Zhang, Xudong Liu, Jiangang Zhang, Liwen Kuang, Jiongming Chen, Yijiao Chen, Dairong Li, Yongsheng Li

{"title":"Carcinoembryonic antigen potentiates non-small cell lung cancer progression via PKA-PGC-1ɑ axis.","authors":"Juan Lei, Lei Wu, Nan Zhang, Xudong Liu, Jiangang Zhang, Liwen Kuang, Jiongming Chen, Yijiao Chen, Dairong Li, Yongsheng Li","doi":"10.1186/s43556-024-00181-3","DOIUrl":"10.1186/s43556-024-00181-3","url":null,"abstract":"Carcinoembryonic antigen (CEA) is a tumor-associated antigen primarily produced by tumor cells. It has been implicated in various biological processes such as cell adhesion, proliferation, differentiation, and metastasis. Despite this, the precise molecular mechanisms through which CEA enhances tumor cell proliferation remain largely unclear. Our study demonstrates that CEA enhances the proliferation and migration of non-small cell lung cancer (NSCLC) while also inhibiting cisplatin-induced apoptosis in NSCLC cells. Treatment with CEA led to an increase in mitochondrial numbers and accumulation of lipid droplets in A549 and H1299 cells. Additionally, our findings indicate that CEA plays a role in regulating the fatty acid metabolism of NSCLC cells. Inhibiting fatty acid metabolism significantly reduced the CEA-mediated proliferation and migration of NSCLC cells. CEA influences fatty acid metabolism and the proliferation of NSCLC cells by activating the PGC-1α signaling pathway. This regulatory mechanism involves CEA increasing intracellular cAMP levels, which in turn activates PKA and upregulates PGC-1α. In NSCLC, inhibiting the PKA-PGC-1α signaling pathway reduces both fatty acid metabolism and the proliferation and migration induced by CEA, both in vitro and in vivo. These results suggest that CEA contributes to the promotion of proliferation and migration by modulating fatty acid metabolism. Targeting CEA or the PKA-PGC-1ɑ signaling pathway may offer a promising therapeutic approach for treating NSCLC.","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"19"},"PeriodicalIF":6.3,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11116303/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141086317","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}

引用次数: 0