International Journal of Biological Sciences最新文献_第10页

METTL16 Promotes Stability of SYNPO2L mRNA and leading to Cancer Cell Lung Metastasis by Secretion of COL10A1 and attract the Cancer-Associated Fibroblasts. METTL16 通过分泌 COL10A1 和吸引癌症相关成纤维细胞促进 SYNPO2L mRNA 的稳定并导致癌细胞肺转移。

IF 8.2 2区生物学

International Journal of Biological Sciences Pub Date : 2024-08-01 eCollection Date: 2024-01-01 DOI: 10.7150/ijbs.95375

Jianlong Wu, Peng Ouyang, Rui Huang, Yao Cui, Zhihao Yang, Wei Xu, Rui Ma, Guoan Xiang, Wei Zeng, Wang Wu, Jian Li

{"title":"METTL16 Promotes Stability of SYNPO2L mRNA and leading to Cancer Cell Lung Metastasis by Secretion of COL10A1 and attract the Cancer-Associated Fibroblasts.","authors":"Jianlong Wu, Peng Ouyang, Rui Huang, Yao Cui, Zhihao Yang, Wei Xu, Rui Ma, Guoan Xiang, Wei Zeng, Wang Wu, Jian Li","doi":"10.7150/ijbs.95375","DOIUrl":"10.7150/ijbs.95375","url":null,"abstract":"The occurrence of metastasis is a major factor contributing to poor prognosis in colorectal cancer. Different stages of the disease play a crucial role in distant metastasis. Furthermore, m6A has been demonstrated to play a significant role in regulating tumor metastasis. Therefore, we conducted an analysis of transcriptome data from high-stage and low-stage colorectal cancer patients in The Cancer Genome Atlas (TCGA) to identify genes associated with m6A-related regulation. We identified SYNPO2L as a core gene regulated by m6A, and it is correlated with adverse prognosis and metastasis in patients. Additionally, we demonstrated that the m6A writer gene Mettl16 can regulate the stability of SYNPO2L through interaction with YTHDC1. Subsequently, using Weighted Gene Co-expression Network Analysis (WGCNA), we discovered that SYNPO2L can regulate COL10A1, mediating the actions of Cancer-Associated Fibroblasts. SYNPO2L promotes the secretion of COL10A1 and the infiltration of tumor-associated fibroblasts, thereby facilitating Epithelial-Mesenchymal Transition (EMT) in tumor cells and making them more prone to distant metastasis.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11379079/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

N6-methyladenosine modification of LATS2 promotes hepatoblastoma progression by inhibiting ferroptosis through the YAP1/ATF4/PSAT1 axis. LATS2的N6-甲基腺苷修饰通过YAP1/ATF4/PSAT1轴抑制铁突变，从而促进肝母细胞瘤的进展。

IF 8.2 2区生物学

International Journal of Biological Sciences Pub Date : 2024-08-01 eCollection Date: 2024-01-01 DOI: 10.7150/ijbs.92413

Guoqing Zhu, Yi Xie, Zhixuan Bian, Ji Ma, Ni Zhen, Tianshu Chen, Jiabei Zhu, Siwei Mao, Xiaochen Tang, Li Liu, Song Gu, Miao Ding, Qiuhui Pan

{"title":"N6-methyladenosine modification of LATS2 promotes hepatoblastoma progression by inhibiting ferroptosis through the YAP1/ATF4/PSAT1 axis.","authors":"Guoqing Zhu, Yi Xie, Zhixuan Bian, Ji Ma, Ni Zhen, Tianshu Chen, Jiabei Zhu, Siwei Mao, Xiaochen Tang, Li Liu, Song Gu, Miao Ding, Qiuhui Pan","doi":"10.7150/ijbs.92413","DOIUrl":"10.7150/ijbs.92413","url":null,"abstract":"Ferroptosis has attracted extensive interest from cancer researchers due to its substantial potential as a therapeutic target. The role of LATS2, a core component of the Hippo pathway cascade, in ferroptosis initiation in hepatoblastoma (HB) has not yet been investigated. Furthermore, the underlying mechanism of decreased LATS2 expression remains largely unknown. In the present study, we demonstrated decreased LATS2 expression in HB and that LATS2 overexpression inhibits HB cell proliferation by inducing ferroptosis. Increased LATS2 expression reduced glycine and cysteine concentrations via the ATF4/PSAT1 axis. Physical binding between YAP1/ATF4 and the PSAT1 promoter was confirmed through ChIP‒qPCR. Moreover, METTL3 was identified as the writer of the LATS2 mRNA m6A modification at a specific site in the 5' UTR. Subsequently, YTHDF2 recognizes the m6A modification site and recruits the CCR4-NOT complex, leading to its degradation by mRNA deadenylation. In summary, N6-methyladenosine modification of LATS2 facilitates its degradation. Reduced LATS2 expression promotes hepatoblastoma progression by inhibiting ferroptosis through the YAP1/ATF4/PSAT1 axis. Targeting LATS2 is a potential strategy for HB therapy.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11379071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Catalpol attenuates hepatic glucose metabolism disorder and oxidative stress in triptolide-induced liver injury by regulating the SIRT1/HIF-1α pathway. 梓醇通过调节SIRT1/HIF-1α途径减轻三苯氧胺诱导的肝损伤中的肝糖代谢紊乱和氧化应激。

IF 8.2 2区生物学

International Journal of Biological Sciences Pub Date : 2024-08-01 eCollection Date: 2024-01-01 DOI: 10.7150/ijbs.97362

Weijue Nie, Hong Zhu, Xin Sun, Jie Zhou, Heng Xu, Zhichao Yu, Minghao Lu, Baoping Jiang, Lingling Zhou, Xueping Zhou

{"title":"Catalpol attenuates hepatic glucose metabolism disorder and oxidative stress in triptolide-induced liver injury by regulating the SIRT1/HIF-1α pathway.","authors":"Weijue Nie, Hong Zhu, Xin Sun, Jie Zhou, Heng Xu, Zhichao Yu, Minghao Lu, Baoping Jiang, Lingling Zhou, Xueping Zhou","doi":"10.7150/ijbs.97362","DOIUrl":"10.7150/ijbs.97362","url":null,"abstract":"Triptolide (TP), known for its effectiveness in treating various rheumatoid diseases, is also associated with significant hepatotoxicity risks. This study explored Catalpol (CAT), an iridoid glycoside with antioxidative and anti-inflammatory effects, as a potential defense against TP-induced liver damage. In vivo and in vitro models of liver injury were established using TP in combination with different concentrations of CAT. Metabolomics analyses were conducted to assess energy metabolism in mouse livers. Additionally, a Seahorse XF Analyzer was employed to measure glycolysis rate, mitochondrial respiratory functionality, and real-time ATP generation rate in AML12 cells. The study also examined the expression of proteins related to glycogenolysis and gluconeogenesis. Using both in vitro SIRT1 knockout/overexpression and in vivo liver-specific SIRT1 knockout models, we confirmed SIRT1 as a mechanism of action for CAT. Our findings revealed that CAT could alleviate TP-induced liver injury by activating SIRT1, which inhibited lysine acetylation of hypoxia-inducible factor-1α (HIF-1α), thereby restoring the balance between glycolysis and oxidative phosphorylation. This action improved mitochondrial dysfunction and reduced glucose metabolism disorder and oxidative stress caused by TP. Taken together, these insights unveil a hitherto undocumented mechanism by which CAT ameliorates TP-induced liver injury, positioning it as a potential therapeutic agent for managing TP-induced hepatotoxicity.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11302874/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exosomes: Emerging Insights into the Progression of Pancreatic Cancer. 外泌体：胰腺癌进展的新见解。

IF 8.2 2区生物学

International Journal of Biological Sciences Pub Date : 2024-08-01 eCollection Date: 2024-01-01 DOI: 10.7150/ijbs.97076

Xulin Zhou, Yongmin Yan, Ye Shen, Min Xu, Wenrong Xu

引用次数: 0

FGF7 and FGF10 Promote Fate Transition of Human Epidermal Cell-derived Organoids to an Eccrine Gland Phenotype. FGF7和FGF10促进人表皮细胞衍生的器官组织向生殖腺表型的命运转变

IF 8.2 2区生物学

International Journal of Biological Sciences Pub Date : 2024-08-01 eCollection Date: 2024-01-01 DOI: 10.7150/ijbs.97422

Junhong Zhao, Lei Zhang, Yonghong Zhang, Manxiu Cao, Cangyu Wang, Anqi Hu, Leilei Cao, Qizhi Luo, Zhen You, Xueping Ma, Liang Gong, Cuiping Zhang, Haihong Li

{"title":"FGF7 and FGF10 Promote Fate Transition of Human Epidermal Cell-derived Organoids to an Eccrine Gland Phenotype.","authors":"Junhong Zhao, Lei Zhang, Yonghong Zhang, Manxiu Cao, Cangyu Wang, Anqi Hu, Leilei Cao, Qizhi Luo, Zhen You, Xueping Ma, Liang Gong, Cuiping Zhang, Haihong Li","doi":"10.7150/ijbs.97422","DOIUrl":"10.7150/ijbs.97422","url":null,"abstract":"Rationale: Reconstruction of hair follicles (HFs) and eccrine sweat glands (ESGs) is essential for functional skin regeneration. In skin reconstruction research, we found that foreskin-derived epidermal cells reconstructed HF organoids unidirectionally, but not ESG organoids. Methods: To investigate key genes and pathways influencing the fate of ESG and HF, a transcriptome profiling of ESG placode-containing skin and HF placode-containing skin was employed, and key DEGs were identified and validated by RT-qPCR and immunofluorescence staining in mice and rats. Subsequently, adult human epidermal cell-derived organoids were reconstructed to probe functional roles and mechanisms of FGF7 and FGF10 by series of approaches integrating RT-qPCR, immunofluorescence-staining, WB, apoptosis assay, and pathway interference assay. Results: All members of FGF7 subfamily were among the key DEGs screened, the differential expression of FGF7 and FGF10 and their receptors FGFR1/FGFR2 was verified between ESG placode-containing skin and HF placode-containing skin. In vivo and in vitro Matrigel plug models showed that both FGF7 and FGF10 promoted fate transition of human epidermal cell-derived organoids to ESG phenotype organoids, FGF7 and FGF10 had a synergistic effect, and mainly function through the FGFR1/2-MEK1/2-ERK1/2 pathway. Conclusions: Adult epidermal cells can be manipulated to reconstruct personalized HF and ESG to meet different needs.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11379064/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

NRF2-HIF2α Signaling Attenuates Endothelial Cell Senescence and Maintains Intercellular Junctions in Diabetes. NRF2-HIF2α信号传导可减轻糖尿病内皮细胞衰老并维持细胞间连接

IF 8.2 2区生物学

International Journal of Biological Sciences Pub Date : 2024-07-22 eCollection Date: 2024-01-01 DOI: 10.7150/ijbs.96719

Jian Shen, Yifan Lai, Yaner Lu, Yabin Liu, Jinlong Zhang, Yan Wu, Yunan Pan, Haibo Chen, Qiyue Gao, Qucheng Wei, Yuwen Chen, Jian Ye, Yinuo Lin, Bingchen Liu, Jun Jiang, Jinliang Nan

{"title":"NRF2-HIF2α Signaling Attenuates Endothelial Cell Senescence and Maintains Intercellular Junctions in Diabetes.","authors":"Jian Shen, Yifan Lai, Yaner Lu, Yabin Liu, Jinlong Zhang, Yan Wu, Yunan Pan, Haibo Chen, Qiyue Gao, Qucheng Wei, Yuwen Chen, Jian Ye, Yinuo Lin, Bingchen Liu, Jun Jiang, Jinliang Nan","doi":"10.7150/ijbs.96719","DOIUrl":"10.7150/ijbs.96719","url":null,"abstract":"In the context of diabetes, endothelial cells frequently exhibit compromised intercellular junctions and accelerated cellular senescence simultaneously. The precise mechanisms underlying these issues and the identification of effective treatments remain largely undefined. Our findings reveal that human umbilical vein endothelial cells (HUVECs) can counteract senescence and uphold the integrity of intercellular junctions under mildly to moderately elevated glucose levels (10 mM and 15 mM) via two primary mechanisms: i) The acetylation of NRF2 at lysine residues K56, K68, and K52 prevents its ubiquitination, enhancing the transcription of antioxidant genes GST, SOD1, and GPX1. This activity diminishes cytoplasmic oxidative stress, thereby mitigating endothelial cell senescence. ii) The interaction between the Neh2 domain of NRF2 and the PAS-B domain of HIF-2α within the nucleus curtails the attachment of HIF-2α to the NOX4/p22phox promoter. This action lessens oxidative stress near the cell membrane, maintaining intercellular junctions by safeguarding the disulfide bonds in occludin and E-cadherin from disruption. However, these protective strategies prove insufficient under severe hyperglycemic conditions (25 mM). Further investigation has identified Oltipraz, an activator of NRF2, as also promoting the degradation of HIF-2α. Through its simultaneous modulation of NRF2 and HIF-2α, Oltipraz significantly reduces cellular senescence and prevents the deterioration of intercellular junctions in HUVECs subjected to high glucose concentrations (25 mM). Our research positions Oltipraz as a promising therapeutic candidate for mitigating diabetes-induced vascular endothelial damage, potentially offering benefits against diabetes-related atherosclerosis and valvular calcification.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11302875/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Nephron-Specific Lin28A Overexpression Triggers Severe Inflammatory Response and Kidney Damage. 肾小球特异性 Lin28A 过表达引发严重炎症反应和肾损伤

IF 8.2 2区生物学

International Journal of Biological Sciences Pub Date : 2024-07-22 eCollection Date: 2024-01-01 DOI: 10.7150/ijbs.97434

Anna Futorian, Leah Armon, Hiba Waldman Ben-Asher, Irit Shoval, Inbal Hazut, Ariel Munitz, Achia Urbach

{"title":"Nephron-Specific Lin28A Overexpression Triggers Severe Inflammatory Response and Kidney Damage.","authors":"Anna Futorian, Leah Armon, Hiba Waldman Ben-Asher, Irit Shoval, Inbal Hazut, Ariel Munitz, Achia Urbach","doi":"10.7150/ijbs.97434","DOIUrl":"10.7150/ijbs.97434","url":null,"abstract":"The RNA-binding proteins LIN28A and LIN28B contribute to a variety of developmental biological processes. Dysregulation of Lin28A and Lin28B expression is associated with numerous types of tumors. This study demonstrates that Lin28A overexpression in the mouse nephrons leads to severe inflammation and kidney damage rather than to tumorigenesis. Notably, Lin28A overexpression causes inflammation only when expressed in nephrons, but not in the stromal cells of the kidneys, highlighting its cell context-dependent nature. The nephron-specific Lin28A-induced inflammatory response differs from previously described Lin28B-mediated inflammatory feedback loops as it is IL-6 independent. Instead, it is associated with the rapid upregulation of cytokines like Cxcl1 and Ccl2. These findings suggest that the pathophysiological effects of Lin28A overexpression extend beyond cell transformation. Our transgenic mouse model offers a valuable tool for advancing our understanding of the pathophysiology of acute kidney injury, where inflammation is a key factor.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11302891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

tRF-27 competitively Binds to G3BPs and Activates MTORC1 to Enhance HER2 Positive Breast Cancer Trastuzumab Tolerance. tRF-27 与 G3BPs 竞争性结合并激活 MTORC1，从而增强 HER2 阳性乳腺癌对曲妥珠单抗的耐受性。

IF 8.2 2区生物学

International Journal of Biological Sciences Pub Date : 2024-07-15 eCollection Date: 2024-01-01 DOI: 10.7150/ijbs.87415

Yaozhou He, Yincheng Liu, Jue Gong, Fan Yang, Chunxiao Sun, Xueqi Yan, Ningjun Duan, Yijia Hua, Tianyu Zeng, Ziyi Fu, Yan Liang, Wei Li, Xiang Huang, Jinhai Tang, Yongmei Yin

{"title":"tRF-27 competitively Binds to G3BPs and Activates MTORC1 to Enhance HER2 Positive Breast Cancer Trastuzumab Tolerance.","authors":"Yaozhou He, Yincheng Liu, Jue Gong, Fan Yang, Chunxiao Sun, Xueqi Yan, Ningjun Duan, Yijia Hua, Tianyu Zeng, Ziyi Fu, Yan Liang, Wei Li, Xiang Huang, Jinhai Tang, Yongmei Yin","doi":"10.7150/ijbs.87415","DOIUrl":"10.7150/ijbs.87415","url":null,"abstract":"About 20% of breast cancer patients are positive for HER2. The efficacy of current treatments is limited by primary and secondary resistance to trastuzumab. tRNA-derived fragments (tRFs) have shown crucial regulatory roles in various cancers. This study aimed to evaluate the role of tRF-27 in regulating the resistance of HER2-positive breast cancer against trastuzumab. tRF-27 was highly expressed in trastuzumab-resistant cells, and its expression level could predict the resistance to trastuzumab. High expression of tRF-27 promoted the growth and proliferation of trastuzumab-exposed cells. RNA-pulldown assay and mass spectrometry were performed to identify Ras GTPase-activating protein-binding proteins 1 and 2 (G3BPs) (two proteins targeted by tRF-27); RNA-immunoprecipitation (RIP) to confirm their bindings; co-immunoprecipitation (co-IP) and RNA-pulldown assay to determine the binding domains between G3BPs and tRF-27.tRF-27 bound to the nuclear transport factor 2 like domain(NTF2 domain) of G3BPs through a specific sequence. tRF-27 relied on G3BPs and NTF2 domain to increase trastuzumab tolerance. tRF-27 competed with lysosomal associated membrane protein 1(LAMP1) for NTF2 domain, thereby inhibiting lysosomal localization of G3BPs and tuberous sclerosis complex (TSC). Overexpression of tRF-27 inhibited phosphorylation of TSCs and promoted the activation of mechanistic target of rapamycin complex 1(MTORC1) to enhance cell proliferation and entice the resistance of HER2-positive breast cancer against trastuzumab.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11302882/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Interaction of Calcium-Sensing Receptor with KIF11 Enhances Cisplatin Resistance in Lung Adenocarcinoma via BRCA1/cyclin B1 pathway. 钙传感受体与 KIF11 的相互作用通过 BRCA1/cyclin B1 途径增强了肺腺癌对顺铂的耐药性

IF 8.2 2区生物学

International Journal of Biological Sciences Pub Date : 2024-07-15 eCollection Date: 2024-01-01 DOI: 10.7150/ijbs.92046

Fuhao Wang, Xing Fu, Ming Chang, Tianzi Wei, Risheng Lin, Haibo Tong, Xiao Zhang, Runzhu Yuan, Zhiqing Zhou, Xin Huang, Wei Zhang, Wenmei Su, Yi Lu, Zhen Liang, Jian Zhang

{"title":"The Interaction of Calcium-Sensing Receptor with KIF11 Enhances Cisplatin Resistance in Lung Adenocarcinoma via BRCA1/cyclin B1 pathway.","authors":"Fuhao Wang, Xing Fu, Ming Chang, Tianzi Wei, Risheng Lin, Haibo Tong, Xiao Zhang, Runzhu Yuan, Zhiqing Zhou, Xin Huang, Wei Zhang, Wenmei Su, Yi Lu, Zhen Liang, Jian Zhang","doi":"10.7150/ijbs.92046","DOIUrl":"10.7150/ijbs.92046","url":null,"abstract":"Cisplatin (DDP) is commonly used in the treatment of non-small cell lung cancer (NSCLC), including lung adenocarcinoma (LUAD), and the primary cause for its clinical inefficacy is chemoresistance. Here, we aimed to investigate a novel mechanism of chemoresistance in LUAD cells, focusing on the calcium-sensing receptor (CaSR). In this study, high CaSR expression was detected in DDP-resistant LUAD cells, and elevated CaSR expression is strongly correlated with poor prognosis in LUAD patients receiving chemotherapy. LUAD cells with high CaSR expression exhibited decreased sensitivity to cisplatin, and the growth of DDP-resistant LUAD cells was inhibited by cisplatin treatment in combination with CaSR suppression, accompanied by changes in BRCA1 and cyclin B1 protein expression both in vitro and in vivo. Additionally, an interaction between CaSR and KIF11 was identified. Importantly, suppressing KIF11 resulted in decreased protein levels of BRCA1 and cyclin B1, enhancing the sensitivity of DDP-resistant LUAD cells to cisplatin with no obvious decrease in CaSR. Here, our findings established the critical role of CaSR in promoting cisplatin resistance in LUAD cells by modulating cyclin B1 and BRCA1 and identified KIF11 as a mediator, highlighting the potential therapeutic value of targeting CaSR to overcome chemoresistance in LUAD.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11302892/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","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 PCSK9 enhances the anti-hepatocellular carcinoma effects of TCR-T cells and anti-PD-1 immunotherapy. 抑制 PCSK9 可增强 TCR-T 细胞和抗 PD-1 免疫疗法的抗肝细胞癌效果。

IF 8.2 2区生物学

International Journal of Biological Sciences Pub Date : 2024-07-15 eCollection Date: 2024-01-01 DOI: 10.7150/ijbs.93668

Weikang Xu, Minli Hu, Xinyu Lu, Yueqiong Lao, Na Ma, Yiyue Wang, Jing Li, Xingyuan Chen, Shiming Liu, Jing Liu, Wei Zhu, Hui Yang

{"title":"Inhibition of PCSK9 enhances the anti-hepatocellular carcinoma effects of TCR-T cells and anti-PD-1 immunotherapy.","authors":"Weikang Xu, Minli Hu, Xinyu Lu, Yueqiong Lao, Na Ma, Yiyue Wang, Jing Li, Xingyuan Chen, Shiming Liu, Jing Liu, Wei Zhu, Hui Yang","doi":"10.7150/ijbs.93668","DOIUrl":"10.7150/ijbs.93668","url":null,"abstract":"T cells play important roles in antitumor immunity. However, given that the hepatocellular carcinoma (HCC) tumor microenvironment confers resistance to T cell-based immunotherapies, novel strategies to boost T cell-mediated antitumor efficacy are urgently needed for the treatment of HCC. Here, we show that high proprotein convertase subtilisin/kexin type9 (PCSK9) expression was negatively associated with HCC patient's overall survival and markers of CD8+ T cells. Pharmacological inhibition of PCSK9 enhanced tumor-specific killing and downregulated PD-1 expression of AFP-specific TCR-T. Inhibition of PCSK9 significantly enhances the anti-HCC efficacy of TCR-T cells and anti-PD-1 immunotherapy in vivo. Moreover, PCSK9 inhibitor suppressed HCC growth dependent on CD8+ T cells. Mechanically, pharmacological inhibition of PCSK9 promoted low-density lipoprotein receptor (LDLR)-mediated activation of mTORC1 signaling in CD8+ T cells. LDLR deficiency was shown to impair cellular mTORC1 signaling and the anti-HCC function of CD8 T cells. On the basis of our findings in this study, we propose a potential metabolic intervention strategy that could be used to enhance the antitumor effects of immunotherapy for HCC.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11302870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141904158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0