Cell Death Discovery最新文献_第4页

Author Correction: Human adipose tissue-derived mesenchymal stem cells and their extracellular vesicles modulate lipopolysaccharide activated human microglia. 作者更正：人脂肪组织间充质干细胞及其细胞外囊泡可调节脂多糖激活的人小胶质细胞。

IF 6.1 2区生物学

Cell Death Discovery Pub Date : 2024-10-23 DOI: 10.1038/s41420-024-02209-7

Marta Garcia-Contreras, Avnesh S Thakor

引用次数: 0

Long non-coding RNA-encoded micropeptides: functions, mechanisms and implications. 长非编码 RNA 编码的微肽：功能、机制和影响。

IF 6.1 2区生物学

Cell Death Discovery Pub Date : 2024-10-23 DOI: 10.1038/s41420-024-02175-0

Yinan Xiao, Yaru Ren, Wenteng Hu, Athanasios R Paliouras, Wenyang Zhang, Linghui Zhong, Kaixin Yang, Li Su, Peng Wang, Yonghong Li, Minjie Ma, Lei Shi

{"title":"Long non-coding RNA-encoded micropeptides: functions, mechanisms and implications.","authors":"Yinan Xiao, Yaru Ren, Wenteng Hu, Athanasios R Paliouras, Wenyang Zhang, Linghui Zhong, Kaixin Yang, Li Su, Peng Wang, Yonghong Li, Minjie Ma, Lei Shi","doi":"10.1038/s41420-024-02175-0","DOIUrl":"https://doi.org/10.1038/s41420-024-02175-0","url":null,"abstract":"Long non-coding RNAs (lncRNAs) are typically described as RNA transcripts exceeding 200 nucleotides in length, which do not code for proteins. Recent advancements in technology, including ribosome RNA sequencing and ribosome nascent-chain complex sequencing, have demonstrated that many lncRNAs retain small open reading frames and can potentially encode micropeptides. Emerging studies have revealed that these micropeptides, rather than lncRNAs themselves, are responsible for vital functions, including but not limited to regulating homeostasis, managing inflammation and the immune system, moderating metabolism, and influencing tumor progression. In this review, we initially outline the rapidly advancing computational analytical methods and public tools to predict and validate the potential encoding of lncRNAs. We then focus on the diverse functions of micropeptides and their underlying mechanisms in the pathogenesis of disease. This review aims to elucidate the functions of lncRNA-encoded micropeptides and explore their potential applications as therapeutic targets in cancer.","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"10 1","pages":"450"},"PeriodicalIF":6.1,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11499885/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495900","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

C/EBPα-mediated ACSL4-dependent ferroptosis exacerbates tubular injury in diabetic kidney disease. C/EBPα介导的 ACSL4 依赖性铁蛋白沉积会加剧糖尿病肾病的肾小管损伤。

IF 6.1 2区生物学

Cell Death Discovery Pub Date : 2024-10-23 DOI: 10.1038/s41420-024-02179-w

Ziru Xia, Zhaonan Wei, Xin Li, Yunzi Liu, Xiangchen Gu, Jianhua Tong, Siyi Huang, Xiaoyue Zhang, Weiming Wang

{"title":"C/EBPα-mediated ACSL4-dependent ferroptosis exacerbates tubular injury in diabetic kidney disease.","authors":"Ziru Xia, Zhaonan Wei, Xin Li, Yunzi Liu, Xiangchen Gu, Jianhua Tong, Siyi Huang, Xiaoyue Zhang, Weiming Wang","doi":"10.1038/s41420-024-02179-w","DOIUrl":"https://doi.org/10.1038/s41420-024-02179-w","url":null,"abstract":"Diabetic kidney disease (DKD) is a prevalent and debilitating complication of diabetes characterized by progressive renal function decline and a lack of effective treatment options. Here, we investigated the role of the transcription factor CCAAT/enhancer binding protein alpha (C/EBPα) in DKD pathogenesis. Analysis of renal biopsy samples revealed increased C/EBPα expression in patients with DKD. Using RNA sequencing and proteomics, we explored the mechanisms through which the C/EBPα contributes to DKD. Our findings demonstrated that C/EBPα exacerbated tubular injury by promoting acyl-CoA synthetase long-chain family member 4 (ACSL4)-dependent ferroptosis. We identified that C/EBPα upregulated ACSL4 expression by binding to its transcription regulatory sequence (TRS), leading to elevated lipid peroxidation and ferroptosis. Furthermore, inhibition or genetic ablation of C/EBPα attenuated ferroptosis and mitigated tubular injury in DKD. These results highlighted the C/EBPα-ACSL4-ferroptosis pathway as a promising therapeutic target for DKD treatment.","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"10 1","pages":"448"},"PeriodicalIF":6.1,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11499655/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495897","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

Mutation of the SUMOylation site of Aurora-B disrupts spindle formation and chromosome alignment in oocytes. Aurora-B 的 SUMOylation 位点突变会破坏卵母细胞中纺锤体的形成和染色体的排列。

IF 6.1 2区生物学

Cell Death Discovery Pub Date : 2024-10-22 DOI: 10.1038/s41420-024-02217-7

Shan-Shan Chen, Li Li, Bo Yao, Jia-Lun Guo, Ping-Shuang Lu, Hao-Lin Zhang, Kun-Huan Zhang, Yuan-Jing Zou, Nan-Jian Luo, Shao-Chen Sun, Lin-Lin Hu, Yan-Ping Ren

{"title":"Mutation of the SUMOylation site of Aurora-B disrupts spindle formation and chromosome alignment in oocytes.","authors":"Shan-Shan Chen, Li Li, Bo Yao, Jia-Lun Guo, Ping-Shuang Lu, Hao-Lin Zhang, Kun-Huan Zhang, Yuan-Jing Zou, Nan-Jian Luo, Shao-Chen Sun, Lin-Lin Hu, Yan-Ping Ren","doi":"10.1038/s41420-024-02217-7","DOIUrl":"https://doi.org/10.1038/s41420-024-02217-7","url":null,"abstract":"Aurora-B is a kinase that regulates spindle assembly and kinetochore-microtubule (KT-MT) attachment during mitosis and meiosis. SUMOylation is involved in the oocyte meiosis regulation through promoting spindle assembly and chromosome segregation, but its substrates to support this function is still unknown. It is reported that Aurora-B is SUMOylated in somatic cells, and SUMOylated Aurora-B contributes the process of mitosis. However, whether Aurora-B is SUMOylated in oocytes and how SUMOylation of Aurora-B impacts its function in oocyte meiosis remain poorly understood. In this study, we report that Aurora-B is modified by SUMOylation in mouse oocytes. The results show that Aurora-B colocalized and interacted with SUMO-2/3 in mouse oocytes, confirming that Aurora-B is modified by SUMO-2/3 in this system. Compared with that in young mice, the protein expression of SUMO-2/3 decreased in the oocytes of aged mice, indicating that SUMOylation might be related to mouse aging. Overexpression of Aurora-B SUMOylation site mutants, Aurora-BK207R and Aurora-BK292R, inhibited Aurora-B recruitment and first polar body extrusion, disrupting localization of gamma tubulin, spindle formation and chromosome alignment in oocytes. The results show that it was related to decreased recruitment of p-HDAC6 which induces the high stability of whole spindle microtubules including the microtubules of both correct and wrong KT-MT attachments though increased acetylation of microtubules. Therefore, our results corroborate the notion that Aurora-B activity is regulated by SUMO-2/3 in oocytes, and that SUMOylated Aurora B plays an important role in spindle formation and chromosome alignment.","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"10 1","pages":"447"},"PeriodicalIF":6.1,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11496499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495901","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

Upregulation of cholinergic modulators Lypd6 and Lypd6b associated with autism drives anxiety and cognitive decline. 与自闭症相关的胆碱能调节剂 Lypd6 和 Lypd6b 的上调会导致焦虑和认知能力下降。

IF 6.1 2区生物学

Cell Death Discovery Pub Date : 2024-10-21 DOI: 10.1038/s41420-024-02211-z

Aizek B Isaev, Maxim L Bychkov, Dmitrii S Kulbatskii, Alexander A Andreev-Andrievskiy, Mikhail A Mashkin, Mikhail A Shulepko, Olga V Shlepova, Eugene V Loktyushov, Alexander V Latanov, Mikhail P Kirpichnikov, Ekaterina N Lyukmanova

{"title":"Upregulation of cholinergic modulators Lypd6 and Lypd6b associated with autism drives anxiety and cognitive decline.","authors":"Aizek B Isaev, Maxim L Bychkov, Dmitrii S Kulbatskii, Alexander A Andreev-Andrievskiy, Mikhail A Mashkin, Mikhail A Shulepko, Olga V Shlepova, Eugene V Loktyushov, Alexander V Latanov, Mikhail P Kirpichnikov, Ekaterina N Lyukmanova","doi":"10.1038/s41420-024-02211-z","DOIUrl":"10.1038/s41420-024-02211-z","url":null,"abstract":"Intellectual disability and autistic features are associated with chromosome region 2q23.q23.2 duplication carrying LYPD6 and LYPD6B genes. Here, we analyzed LYPD6 and LYPD6B expression in patients with different neuropsychiatric disorders. Increased LYPD6 and LYPD6B expression was revealed in autism and other disorders. To study possible consequences of Lypd6 and Lypd6b overexpression in the brain, we used a mouse model with intracerebroventricular delivery of recombinant analogs of these proteins. A two-week infusion evoked significant memory impairment and acute stress. Both modulators downregulated hippocampal and amygdala dendritic spine density. No changes in synaptic plasticity were observed. Intracerebroventricular administration by both proteins downregulated hippocampal expression of Lypd6, Lypd6b, and α7 nicotinic acetylcholine receptor (nAChR). Similar to Lypd6, Lypd6b targeted different nAChR subtypes in the brain with preferential inhibition of α7- and α4β2-nAChRs. Thus, increased Lypd6 and Lypd6b level in the brain are linked to cholinergic system depression, neuronal atrophy, memory decline, and anxiety.","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"10 1","pages":"444"},"PeriodicalIF":6.1,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11494011/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142485660","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

Sleep restriction exacerbates cardiac dysfunction in diabetic mice by causing cardiomyocyte death and fibrosis through mitochondrial damage. 睡眠限制通过线粒体损伤导致心肌细胞死亡和纤维化，从而加剧糖尿病小鼠的心脏功能障碍。

IF 6.1 2区生物学

Cell Death Discovery Pub Date : 2024-10-21 DOI: 10.1038/s41420-024-02214-w

Jingyi Zhang, Xu Zhao, Jing Tang, Ce Liu, Yining Zhang, Cheng Cai, Qingfeng Du

{"title":"Sleep restriction exacerbates cardiac dysfunction in diabetic mice by causing cardiomyocyte death and fibrosis through mitochondrial damage.","authors":"Jingyi Zhang, Xu Zhao, Jing Tang, Ce Liu, Yining Zhang, Cheng Cai, Qingfeng Du","doi":"10.1038/s41420-024-02214-w","DOIUrl":"10.1038/s41420-024-02214-w","url":null,"abstract":"Diabetic cardiomyopathy (DCM) is a cardiovascular complication of diabetes mellitus with a poor prognosis and is the leading cause of death in diabetic patients. Sleep deficiency is not only recognized as an important risk factor for the development of type 2 DM, but is also associated with increased morbidity and mortality of cardiovascular disease. The underlying role and mechanisms of sleep restriction (SR) in DCM are far from clear. The KK/Upj-Ay mouse model of T2 DM was used as a study subject, and the small animal ultrasound imaging system was used to detect the function of the heart; immunopathological staining was used to clarify the histo-structural pathological alterations of the heart; and TUNEL staining, qPCR, transmission electron microscopy (TEM), and ELISA kits were used to detect apoptosis, oxidative stress, inflammation, and mitochondrial damage, and related molecular alterations. SR led to a significant increase in mortality, cardiac hypertrophy, necrosis, glycogen deposition and fibrosis further deteriorated in DM KK mice. SR increased cardiomyocyte death in KK mice through the Bax/Bcl2 pathway. In addition to this, SR not only exacerbated the inflammatory response, but also aggravated mitochondrial damage and promoted oxidative stress in KK mice through the PRDM16-PGC-1α pathway. Overall, SR exacerbates structural alterations and dysfunction through inflammation, oxidative stress, and apoptosis in DM KK mice, increasing the risk of death. Clinicians and diabetic patients are prompted to pay attention to sleep habits to avoid accelerating the transition of DCM to heart failure and inducing death due to poor sleep habits.","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"10 1","pages":"446"},"PeriodicalIF":6.1,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11494183/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459037","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

Emerging roles of noncoding RNAs in idiopathic pulmonary fibrosis. 非编码 RNA 在特发性肺纤维化中的新作用。

IF 6.1 2区生物学

Cell Death Discovery Pub Date : 2024-10-21 DOI: 10.1038/s41420-024-02170-5

Haitao Wang, Kai Sun, Hao Peng, Yi Wang, Lei Zhang

引用次数: 0

Mitochondrial-derived peptides, HNG and SHLP3, protect cochlear hair cells against gentamicin. 线粒体衍生肽 HNG 和 SHLP3 可保护耳蜗毛细胞免受庆大霉素的伤害。

IF 6.1 2区生物学

Cell Death Discovery Pub Date : 2024-10-21 DOI: 10.1038/s41420-024-02215-9

Yu Lu, Ewelina M Bartoszek, Maurizio Cortada, Daniel Bodmer, Soledad Levano Huaman

{"title":"Mitochondrial-derived peptides, HNG and SHLP3, protect cochlear hair cells against gentamicin.","authors":"Yu Lu, Ewelina M Bartoszek, Maurizio Cortada, Daniel Bodmer, Soledad Levano Huaman","doi":"10.1038/s41420-024-02215-9","DOIUrl":"10.1038/s41420-024-02215-9","url":null,"abstract":"Preservation of hair cells is critical for maintaining hearing function, as damage to sensory cells potentially leads to irreparable sensorineural hearing loss. Hair cell loss is often associated with inflammation and oxidative stress. One promising class of bioactive peptides is mitochondrial-derived peptides (MDPs), which have already been proven to protect various tissues from cellular stresses and delay aging processes. Humanin (HN) is one of the best-known members of this family, and recently, we have shown its protective effect in hair cells. The synthetic derivate HN S14G (HNG) has a more potent protective effect than natural HN making it a more useful peptide candidate to promote cytoprotection. A less-known MDP is small humanin-like peptide 3 (SHLP3), which has cytoprotective effects similar to HN, but likely acts through different signaling pathways. Therefore, we examined the effect of exogenous HNG and SHLP3 in auditory hair cells and investigated the molecular mechanisms involved. For this purpose, explants of the organ of Corti (OC) were treated with gentamicin in the presence and absence of HNG or SHLP3. Administration of HNG and SHLP3 reduced gentamicin-induced hair cell loss. The protective mechanisms of HNG and SHLP3 in OC explants included, in part, modulation of AKT and AMPKα. In addition, treatment with HNG and SHLP3 reduced gentamicin-induced oxidative stress and inflammatory gene overexpression. Overall, our data show that HNG and SHLP3 protect hair cells from gentamicin-induced toxicity. This offers new perspectives for the development of therapeutic strategies with MDPs against hearing loss.","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"10 1","pages":"445"},"PeriodicalIF":6.1,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11493991/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459033","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

RSK2-mediated cGAS phosphorylation induces cGAS chromatin-incorporation-mediated cell transformation and cancer cell colony growth. RSK2- 介导的 cGAS 磷酸化可诱导 cGAS 染色质整合介导的细胞转化和癌细胞集落生长。

IF 6.1 2区生物学

Cell Death Discovery Pub Date : 2024-10-18 DOI: 10.1038/s41420-024-02208-8

Weidong Chen, Ga-Eun Lee, Dohyun Jeung, Jiin Byun, Juan Wu, Xianzhe Li, Joo Young Lee, Han Chang Kang, Hye Suk Lee, Kwang Dong Kim, Soo-Bin Nam, Cheol-Jung Lee, Young Jik Kwon, Yong-Yeon Cho

{"title":"RSK2-mediated cGAS phosphorylation induces cGAS chromatin-incorporation-mediated cell transformation and cancer cell colony growth.","authors":"Weidong Chen, Ga-Eun Lee, Dohyun Jeung, Jiin Byun, Juan Wu, Xianzhe Li, Joo Young Lee, Han Chang Kang, Hye Suk Lee, Kwang Dong Kim, Soo-Bin Nam, Cheol-Jung Lee, Young Jik Kwon, Yong-Yeon Cho","doi":"10.1038/s41420-024-02208-8","DOIUrl":"10.1038/s41420-024-02208-8","url":null,"abstract":"Cyclic guanosine-adenosine monophosphate synthase (cGAS) is a key cytosolic DNA sensor that plays a pivotal role in the innate immune response. Although a decade of research on the cGAS has advanced our understanding of inflammasome formation, cytokine production, and signaling pathways, the role of cGAS in the nucleus remains unclear. In this study, we found that the nuclear localization of endogenous and stably expressed cGAS differed from transiently expressed cGAS, which mainly localized in the cytosol. In the nucleus, cGAS is tightly bound to chromatin DNA. The chromatin DNA binding of cGAS was dependent on RSK2. Our molecular mechanism study indicated that the N-lobe of RSK2 harboring 1-323 interacted with the NTase domain of cGAS harboring residues 213-330. This interaction increased RSK2-induced cGAS phosphorylation at Ser120 and Thr130, resulting in the tightly binding of cGAS to chromatin. Importantly, epidermal growth factor (EGF)-induced cell transformation and anchorage-independent colony growth showed an increase in growth factors, such as EGF or bFGF, in cGAS stable expression compared to mock expression. Notably, the cGAS-S120A/T130A mutant abolished the increasing effect of cell transformation of JB6 Cl41 cells and colony growth of SK-MEL-2 malignant melanoma cells. The results suggested that cGAS's chromatin DNA binding, which is indispensable to RSK2-dependent phosphorylation of cGAS at Ser120/Thr130, provides the first clue to how cGAS may participate in chromatin remodeling in the nucleus.","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"10 1","pages":"442"},"PeriodicalIF":6.1,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11492232/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459036","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

TRIM55 restricts the progression of hepatocellular carcinoma through ubiquitin-proteasome-mediated degradation of NF90. TRIM55 通过泛素蛋白酶介导的 NF90 降解限制肝细胞癌的进展。

IF 6.1 2区生物学

Cell Death Discovery Pub Date : 2024-10-17 DOI: 10.1038/s41420-024-02212-y

Changhong Luo, Yuyan Lu, Qinliang Fang, Jing Lu, Ping Zhan, Wenqing Xi, Jinzhu Wang, Xijun Chen, Qin Yao, Fuqiang Wang, Zhenyu Yin, Chengrong Xie

{"title":"TRIM55 restricts the progression of hepatocellular carcinoma through ubiquitin-proteasome-mediated degradation of NF90.","authors":"Changhong Luo, Yuyan Lu, Qinliang Fang, Jing Lu, Ping Zhan, Wenqing Xi, Jinzhu Wang, Xijun Chen, Qin Yao, Fuqiang Wang, Zhenyu Yin, Chengrong Xie","doi":"10.1038/s41420-024-02212-y","DOIUrl":"https://doi.org/10.1038/s41420-024-02212-y","url":null,"abstract":"Hepatocellular carcinoma (HCC) is a prevalent malignant tumor worldwide. Tripartite motif containing 55 (TRIM55), also known as muscle-specific ring finger 2 (Murf2), belongs to the TRIM protein family and serves as an E3 ligase. Recently, the function and mechanism of TRIM55 in the advancement of solid tumors have been elucidated. However, the role of TRIM55 and its corresponding protein substrates in HCC remains incompletely explored. In this study, we observed a significant reduction in TRIM55 expression in HCC tissues. The downregulation of TRIM55 expression correlated with larger tumor size and elevated serum alpha-fetoprotein (AFP), and predicted unfavorable overall and tumor-free survival. Functional experiments demonstrated that TRIM55 suppressed the proliferation, migration, and invasion of HCC cells in vitro, as well as hindered HCC growth and metastasis in vivo. Additionally, TRIM55 exhibited a suppressive effect on HCC angiogenesis. Mechanistically, TRIM55 interacted with nuclear factor 90 (NF90), a double-stranded RNA-binding protein responsible for regulating mRNA stability and gene transcription, thereby facilitating its degradation via the ubiquitin-proteasome pathway. Furthermore, TRIM55 attenuated the association between NF90 and the mRNA of HIF1α and TGF-β2, consequently reducing their stability and inactivating the HIF1α/VEGF and TGFβ/Smad signaling pathways. In conclusion, our findings unveil the important roles of TRIM55 in suppressing the progression of HCC partly by promoting the degradation of NF90 and subsequently modulating its downstream pathways, including HIF1α/VEGF and TGFβ/Smad signaling.","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"10 1","pages":"441"},"PeriodicalIF":6.1,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11487063/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459039","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