BioFactors最新文献_第10页

Nifuroxazide repurposing for protection from diabetes-induced retinal injury in rats: Implication of oxidative stress and JAK/STAT3 axis 呋噻嗪用于保护大鼠免受糖尿病诱导的视网膜损伤：氧化应激和JAK/STAT3轴的意义。

IF 6 3区生物学

BioFactors Pub Date : 2023-09-22 DOI: 10.1002/biof.2011

Nehal M. Elsherbiny, Reem Altemani, Waad Althagfi, Maha Albalawi, Zuhair M. Mohammedsaleh, Mohamed El-Sherbiny, Nada F. Abo El-Magd

{"title":"Nifuroxazide repurposing for protection from diabetes-induced retinal injury in rats: Implication of oxidative stress and JAK/STAT3 axis","authors":"Nehal M. Elsherbiny, Reem Altemani, Waad Althagfi, Maha Albalawi, Zuhair M. Mohammedsaleh, Mohamed El-Sherbiny, Nada F. Abo El-Magd","doi":"10.1002/biof.2011","DOIUrl":"10.1002/biof.2011","url":null,"abstract":"The prevalence of diabetes mellitus (DM) is alarmingly increasing worldwide. Diabetic retinopathy (DR) is a prevailing DM microvascular complication, representing the major cause of blindness in working-age population. Inflammation is a crucial player in DR pathogenesis. JAK/STAT3 axis is a pleotropic cascade that modulates diverse inflammatory events. Nifuroxazide (Nifu) is a commonly used oral antibiotic with reported JAK/STAT3 inhibition activity. The present study investigated the potential protective effect of Nifu against diabetes-induced retinal injury. Effect of Nifu on oxidative stress, JAK/STAT3 axis and downstream inflammatory mediators has been also studied. Diabetes was induced in Sprague Dawley rats by single intraperitoneal injection of streptozotocin (50 mg/kg). Animals were assigned into four groups: normal, Nifu control, DM, and DM + Nifu. Nifu was orally administrated at 25 mg/kg/day for 8 weeks. The effects of Nifu on oxidative stress, JAK/STAT3 axis proteins, inflammatory factors, tight junction proteins, histological, and ultrastructural alterations were evaluated using spectrophotometry, gene and protein analyses, and histological studies. Nifu administration to diabetic rats attenuated histopathological and signs of retinal injury. Additionally, Nifu attenuated retinal oxidative stress, inhibited JAK and STAT3 phosphorylation, augmented the expression of STAT3 signaling inhibitor SOCS3, dampened the expression of transcription factor of inflammation NF-κB, and inflammatory cytokine TNF-α. Collectively, the current study indicated that Nifu alleviated DR progression in diabetic rats, suggesting beneficial retino-protective effect. This can be attributed to blocking JAK/STAT3 axis in retinal tissues with subsequent amelioration of oxidative stress and inflammation.","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2023-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41098593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dietary lithium stimulates female fecundity in Drosophila melanogaster 膳食锂刺激黑腹果蝇的雌性繁殖力

IF 6 3区生物学

BioFactors Pub Date : 2023-09-14 DOI: 10.1002/biof.2007

Katharina Jans, Kai Lüersen, Jakob von Frieling, Thomas Roeder, Gerald Rimbach

{"title":"Dietary lithium stimulates female fecundity in Drosophila melanogaster","authors":"Katharina Jans, Kai Lüersen, Jakob von Frieling, Thomas Roeder, Gerald Rimbach","doi":"10.1002/biof.2007","DOIUrl":"10.1002/biof.2007","url":null,"abstract":"The trace element lithium exerts a versatile bioactivity in humans, to some extend overlapping with in vivo findings in the model organism Drosophila melanogaster. A potentially essential function of lithium in reproduction has been suggested since the 1980s and multiple studies have since been published postulating a regulatory role of lithium in female gametogenesis. However, the impact of lithium on fruit fly egg production has not been at the center of attention to date. In the present study, we report that dietary lithium (0.1–5.0 mM LiCl) substantially improved life time egg production in D. melanogaster w1118 females, with a maximum increase of plus 45% when supplementing 1.0 mM LiCl. This phenomenon was not observed in the insulin receptor mutant InRE19, indicating a potential involvement of insulin-like signaling in the lithium-mediated fecundity boost. Analysis of the whole-body and ovarian transcriptome revealed that dietary lithium affects the mRNA levels of genes encoding proteins related to processes of follicular maturation. To the best of our knowledge, this is the first report on dietary lithium acting as an in vivo fecundity stimulant in D. melanogaster, further supporting the suggested benefit of the trace element in female reproduction.","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2023-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/biof.2007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10232051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Exploring the therapeutic potential of naturally occurring piceatannol in non-communicable diseases 探索天然猕猴桃单酚对非传染性疾病的治疗潜力

IF 6 3区生物学

BioFactors Pub Date : 2023-09-13 DOI: 10.1002/biof.2009

Himanshu Gandhi, Shikha Mahant, Abhishek Kumar Sharma, Deepak Kumar, Kamal Dua, Dinesh Kumar Chellappan, Sachin Kumar Singh, Gaurav Gupta, Alaa A. A. Aljabali, Murtaza M. Tambuwala, Deepak N. Kapoor

{"title":"Exploring the therapeutic potential of naturally occurring piceatannol in non-communicable diseases","authors":"Himanshu Gandhi, Shikha Mahant, Abhishek Kumar Sharma, Deepak Kumar, Kamal Dua, Dinesh Kumar Chellappan, Sachin Kumar Singh, Gaurav Gupta, Alaa A. A. Aljabali, Murtaza M. Tambuwala, Deepak N. Kapoor","doi":"10.1002/biof.2009","DOIUrl":"10.1002/biof.2009","url":null,"abstract":"Piceatannol is a naturally occurring hydroxylated resveratrol analogue that can be found in a variety of fruits and vegetables. It has been documented to have a wide range of beneficial effects, including anti-inflammatory, antioxidant, anti-aging, anti-allergic, antidiabetic, neuroprotective, cardioprotective, and chemopreventive properties. Piceatannol has significantly higher antioxidant activity than resveratrol. Piceatannol has been shown in preclinical studies to have the ability to inhibit or reduce the growth of cancers in various organs such as the brain, breast, lung, colon, cervical, liver, prostate, and skin. However, the bioavailability of Piceatannol is comparatively lower than resveratrol and other stilbenes. Several approaches have been reported in recent years to enhance its bioavailability and biological activity, and clinical trials are required to validate these findings. This review focuses on several aspects of natural stilbene Piceatannol, its chemistry, and its mechanism of action, and its promising therapeutic potential for the prevention and treatment of a wide variety of complex human diseases.","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2023-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10225266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Breast cancer diagnosis and management guided by data augmentation, utilizing an integrated framework of SHAP and random augmentation 利用 SHAP 和随机扩增综合框架，以数据扩增指导乳腺癌诊断和管理。

IF 6 3区生物学

BioFactors Pub Date : 2023-09-11 DOI: 10.1002/biof.1995

Chukwuebuka Joseph Ejiyi, Zhen Qin, Happy Monday, Makuachukwu Bennedith Ejiyi, Chiagoziem Ukwuoma, Thomas Ugochukwu Ejiyi, Victor Kwaku Agbesi, Amarachi Agu, Chiduzie Orakwue

{"title":"Breast cancer diagnosis and management guided by data augmentation, utilizing an integrated framework of SHAP and random augmentation","authors":"Chukwuebuka Joseph Ejiyi, Zhen Qin, Happy Monday, Makuachukwu Bennedith Ejiyi, Chiagoziem Ukwuoma, Thomas Ugochukwu Ejiyi, Victor Kwaku Agbesi, Amarachi Agu, Chiduzie Orakwue","doi":"10.1002/biof.1995","DOIUrl":"10.1002/biof.1995","url":null,"abstract":"Recent research indicates that early detection of breast cancer (BC) is critical in achieving favorable treatment outcomes and reducing the mortality rate associated with it. With the difficulty in obtaining a balanced dataset that is primarily sourced for the diagnosis of the disease, many researchers have relied on data augmentation techniques, thereby having varying datasets with varying quality and results. The dataset we focused on in this study is crafted from SHapley Additive exPlanations (SHAP)-augmentation and random augmentation (RA) approaches to dealing with imbalanced data. This was carried out on the Wisconsin BC dataset and the effectiveness of this approach to the diagnosis of BC was checked using six machine-learning algorithms. RA synthetically generated some parts of the dataset while SHAP helped in assessing the quality of the attributes, which were selected and used for the training of the models. The result from our analysis shows that the performance of the models used generally increased to more than 3% for most of the models using the dataset obtained by the integration of SHAP and RA. Additionally, after diagnosis, it is important to focus on providing quality care to ensure the best possible outcomes for patients. The need for proper management of the disease state is crucial so as to reduce the recurrence of the disease and other associated complications. Thus the interpretability provided by SHAP enlightens the management strategies in this study focusing on the quality of care given to the patient and how timely the care is.","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2023-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10206482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Gut microbiota contribution to selenium deficiency-induced gut–liver inflammation 肠道微生物群对缺硒引起的肠道肝脏炎症的影响

IF 6 3区生物学

BioFactors Pub Date : 2023-09-07 DOI: 10.1002/biof.2006

Guodong Wang, Zhihui Jiang, Yuwei Song, Yueteng Xing, Simin He, P. Boomi

{"title":"Gut microbiota contribution to selenium deficiency-induced gut–liver inflammation","authors":"Guodong Wang, Zhihui Jiang, Yuwei Song, Yueteng Xing, Simin He, P. Boomi","doi":"10.1002/biof.2006","DOIUrl":"10.1002/biof.2006","url":null,"abstract":"There is limited knowledge about the factors that drive gut–liver axis changes after selenium (Se) deficiency-induced gut or liver injuries. Thus, we tested Se deficiency in mice to determine its effects on intestinal bacterial balance and whether it induced liver injury. Serum Se concentration, lipopolysaccharide (LPS) level, and liver injury biomarkers were tested using a biochemical method, while pathological changes in the liver and jejunum were observed via hematoxylin and eosin stain, and a fluorescence spectrophotometer was used to evaluate intestinal permeability. Tight junction (TJ)-related and toll-like receptor (TLR) signaling-related pathway genes and proteins were tested using quantitative polymerase chain reaction, western blotting, immunohistochemistry, and 16S ribosomal ribonucleic acid gene-targeted sequencing of jejunum microorganisms. Se deficiency significantly decreased glutathione peroxidase activity and disrupted the intestinal flora, with the most significant effect being a decrease in Lactobacillus reuteri. The expression of TJ-related genes and proteins decreased significantly with increased treatment time, whereas supplementation with Se, fecal microbiota transplantation, or L. reuteri reversed these decreases. Signs of liver injury and LPS content were significantly increased after intestinal flora imbalance or jejunum injury, and the levels of TLR signaling-related genes were significantly increased. The results indicated that Se deficiency disrupted the microbiota balance, decreased the expression of intestinal TJ factors, and increased intestinal permeability. By contrast, LPS increased due to a bacterial imbalance, which may induce inflammatory liver injury via the TLR4 signaling pathway.","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2023-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10168534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Modulatory effects of point-mutated IL-32θ (A94V) on tumor progression in triple-negative breast cancer cells 点突变 IL-32θ (A94V) 对三阴性乳腺癌细胞肿瘤进展的调节作用

IF 6 3区生物学

BioFactors Pub Date : 2023-09-02 DOI: 10.1002/biof.2005

Hyo-Min Park, Jae-Young Park, Na-Yeon Kim, Jinju Kim, Thu-Huyen Pham, Jin Tae Hong, Do-Young Yoon

{"title":"Modulatory effects of point-mutated IL-32θ (A94V) on tumor progression in triple-negative breast cancer cells","authors":"Hyo-Min Park, Jae-Young Park, Na-Yeon Kim, Jinju Kim, Thu-Huyen Pham, Jin Tae Hong, Do-Young Yoon","doi":"10.1002/biof.2005","DOIUrl":"10.1002/biof.2005","url":null,"abstract":"Breast cancer is a frequently diagnosed cancer and the leading cause of death among women worldwide. Tumor-associated macrophages stimulate cytokines and chemokines, which induce angiogenesis, metastasis, proliferation, and tumor-infiltrating immune cells. Although interleukin-32 (IL-32) has been implicated in the development and modulation of several cancers, its function in breast cancer remains elusive. Mutation of interleukin-32θ (IL-32θ) in the tissues of patients with breast cancer was detected by Sanger sequencing. RT-qPCR was used to detect the mRNA levels of inflammatory cytokines, chemokines, and mediators. The secreted proteins were detected using respective enzyme-linked immunosorbent assays. Evaluation of the inhibitory effect of mutant IL-32θ on proliferation, migration, epithelial–mesenchymal transition (EMT), and cell cycle arrest in breast cancer cells was conducted using MTS assays, migration assays, and Western blotting. A point mutation (281C>T, Ala94Val) was detected in IL-32θ in both breast tumors and adjacent normal tissues, which suppressed the expression of pro-inflammatory factors, EMT factors, and cell cycle related factors. Mutated IL-32θ inhibited the expression of inflammatory factors by regulating the NF-κB pathway. Furthermore, mutated IL-32θ suppressed EMT markers and cell cycle related factors through the FAK/PI3K/AKT pathway. It was inferred that mutated IL-32θ modulates breast cancer progression. Mutated IL-32θ (A94V) inhibited inflammation, EMT, and proliferation in breast cancer by regulating the NF-κB (p65/p50) and FAK-PI3K-GSK3 pathways.","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2023-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10511547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Biochemical and cellular studies of three human 3-phosphoglycerate dehydrogenase variants responsible for pathological reduced L-serine levels 对导致病理性 L-丝氨酸水平降低的三种人类 3-磷酸甘油酸脱氢酶变体的生化和细胞研究。

IF 6 3区生物学

BioFactors Pub Date : 2023-08-31 DOI: 10.1002/biof.2002

Giulia Murtas, Elena Zerbini, Valentina Rabattoni, Zoraide Motta, Laura Caldinelli, Marco Orlando, Francesco Marchesani, Barbara Campanini, Silvia Sacchi, Loredano Pollegioni

{"title":"Biochemical and cellular studies of three human 3-phosphoglycerate dehydrogenase variants responsible for pathological reduced L-serine levels","authors":"Giulia Murtas, Elena Zerbini, Valentina Rabattoni, Zoraide Motta, Laura Caldinelli, Marco Orlando, Francesco Marchesani, Barbara Campanini, Silvia Sacchi, Loredano Pollegioni","doi":"10.1002/biof.2002","DOIUrl":"10.1002/biof.2002","url":null,"abstract":"In the brain, the non-essential amino acid L-serine is produced through the phosphorylated pathway (PP) starting from the glycolytic intermediate 3-phosphoglycerate: among the different roles played by this amino acid, it can be converted into D-serine and glycine, the two main co-agonists of NMDA receptors. In humans, the enzymes of the PP, namely phosphoglycerate dehydrogenase (hPHGDH, which catalyzes the first and rate-limiting step of this pathway), 3-phosphoserine aminotransferase, and 3-phosphoserine phosphatase are likely organized in the cytosol as a metabolic assembly (a “serinosome”). The hPHGDH deficiency is a pathological condition biochemically characterized by reduced levels of L-serine in plasma and cerebrospinal fluid and clinically identified by severe neurological impairment. Here, three single-point variants responsible for hPHGDH deficiency and Neu-Laxova syndrome have been studied. Their biochemical characterization shows that V261M, V425M, and V490M substitutions alter either the kinetic (both maximal activity and Km for 3-phosphoglycerate in the physiological direction) and the structural properties (secondary, tertiary, and quaternary structure, favoring aggregation) of hPHGDH. All the three variants have been successfully ectopically expressed in U251 cells, thus the pathological effect is not due to hindered expression level. At the cellular level, mistargeting and aggregation phenomena have been observed in cells transiently expressing the pathological protein variants, as well as a reduced L-serine cellular level. Previous studies demonstrated that the pharmacological supplementation of L-serine in hPHGDH deficiencies could ameliorate some of the related symptoms: our results now suggest the use of additional and alternative therapeutic approaches.","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2023-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/biof.2002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10178256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Advances in screening, synthesis, modification, and biomedical applications of peptides and peptide aptamers 多肽和多肽适配体的筛选、合成、修饰和生物医学应用方面的进展。

IF 6 3区生物学

BioFactors Pub Date : 2023-08-30 DOI: 10.1002/biof.2001

Yijie Liu, Xiaoling Lu, Meilun Chen, Zheng Wei, Guangnan Peng, Jie Yang, Chunhua Tang, Peng Yu

{"title":"Advances in screening, synthesis, modification, and biomedical applications of peptides and peptide aptamers","authors":"Yijie Liu, Xiaoling Lu, Meilun Chen, Zheng Wei, Guangnan Peng, Jie Yang, Chunhua Tang, Peng Yu","doi":"10.1002/biof.2001","DOIUrl":"10.1002/biof.2001","url":null,"abstract":"Peptides and peptide aptamers have emerged as promising molecules for a wide range of biomedical applications due to their unique properties and versatile functionalities. The screening strategies for identifying peptides and peptide aptamers with desired properties are discussed, including high-throughput screening, display screening technology, and in silico design approaches. The synthesis methods for the efficient production of peptides and peptide aptamers, such as solid-phase peptide synthesis and biosynthesis technology, are described, along with their advantages and limitations. Moreover, various modification techniques are explored to enhance the stability, specificity, and pharmacokinetic properties of peptides and peptide aptamers. This includes chemical modifications, enzymatic modifications, biomodifications, genetic engineering modifications, and physical modifications. Furthermore, the review highlights the diverse biomedical applications of peptides and peptide aptamers, including targeted drug delivery, diagnostics, and therapeutic. This review provides valuable insights into the advancements in screening, synthesis, modification, and biomedical applications of peptides and peptide aptamers. A comprehensive understanding of these aspects will aid researchers in the development of novel peptide-based therapeutics and diagnostic tools for various biomedical challenges.","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2023-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10468765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Downregulation of microRNA-326 enhances ZNF322A expression, transcriptional activity and tumorigenic effects in lung cancer 下调 microRNA-326 会增强 ZNF322A 在肺癌中的表达、转录活性和致瘤作用。

IF 6 3区生物学

BioFactors Pub Date : 2023-08-30 DOI: 10.1002/biof.2004

Shih-Hsuan Huang, Hung-Chia Hsieh, Jiunn-Min Shieh, Wou-Chou Su, Yi-Ching Wang

{"title":"Downregulation of microRNA-326 enhances ZNF322A expression, transcriptional activity and tumorigenic effects in lung cancer","authors":"Shih-Hsuan Huang, Hung-Chia Hsieh, Jiunn-Min Shieh, Wou-Chou Su, Yi-Ching Wang","doi":"10.1002/biof.2004","DOIUrl":"10.1002/biof.2004","url":null,"abstract":"Zinc finger protein ZNF322A is an oncogenic transcription factor. Overexpression of ZNF322A activates pro-metastasis, cancer stemness, and neo-angiogenesis-related genes to enhance lung cancer progression. However, the upstream regulator of ZNF322A is not well defined. Dysregulation of microRNAs (miRNAs) can mediate cancer cell growth, migration, and invasion to promote tumorigenesis. Here, we uncover the mechanism of miRNA-mediated transcriptional regulation in ZNF322A-driven oncogenic events. ZNF322A harbors several putative miRNA-binding sites in the 3′-untranslated region (UTR). We validated that miR-326 downregulated ZNF322A-3′-UTR luciferase activity and mRNA expression. Furthermore, miR-326 suppressed the expression of ZNF322A-driven cancer-associated genes such as cyclin D1 and alpha-adducin. Reconstitution experiments by ectopic overexpression of ZNF322A abolished miR-326-suppressed cancer cell proliferation and cell migration capacity. Moreover, miR-326 attenuated ZNF322A-induced tumor growth and lung tumor metastasis in vivo. Clinically, the expression of miR-326 negatively correlated with ZNF322A mRNA expression in surgically resected tissues from 120 non-small cell lung cancer (NSCLC) patients. Multivariate Cox regression analysis demonstrated that NSCLC patients with low miR-326/high ZNF322A profile showed poor overall survival. Our results reveal that the deregulated expression of miR-326 leads to hyperactivation of ZNF322A-driven oncogenic signaling. Targeting the miR-326/ZNF322A axis would provide new therapeutic strategies for lung cancer patients.","PeriodicalId":8923,"journal":{"name":"BioFactors","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2023-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10476368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Issue Information - Cover 发行信息-封面

IF 6 3区生物学

BioFactors Pub Date : 2023-08-26 DOI: 10.1002/biof.1860

引用次数: 0