Biochemical Genetics最新文献

{"title":"Altered Mitochondrial DNA Copy Number and Telomere Length in Patients with Substance Use Disorder: Correlation with Age, Sex, and Chronic Diseases.","authors":"Teodora Taseva, Yana Koycheva, Rositsa Racheva, Tsveta Raycheva, Yordan Hodzhev, Emilia Nikolova, Mila Ilieva, Maria Krasteva","doi":"10.1007/s10528-024-10981-5","DOIUrl":"https://doi.org/10.1007/s10528-024-10981-5","url":null,"abstract":"<p><p>Substance use disorder (SUD) is a complex condition involving psychological, sociocultural, and genetic factors. In this study, we examined the alternations in mitochondrial DNA copy number (mtDNAcn) and telomere length (TL) and their relationship to demographic, medical, heredity, and substance use characteristics in patients with SUD and healthy controls. We investigated a total cohort of 54 participants: 21 healthy individuals, 17 patients with alcohol dependence (AD), and 16 patients with drug dependence (DD). TL and mtDNAcn were measured using quantitative real-time PCR, with statistical methods used to assess the association between variables. We observed a significant decrease in mtDNAcn in both SUD groups, particularly associated with chronic diseases in the AD group. No significant differences in TL were found among the three groups. Sex-associated analysis revealed a significant mtDNAcn reduction in the DD males and elevated TL in AD males compared to control males. Correlation analyses showed associations between the two biomarkers and age, sex, and chronic diseases. Our findings suggest that leukocyte mtDNAcn is a more sensitive marker than TL in patients with SUD, indicating sex-specific patterns of alterations. These findings require confirmation through larger cohort recruitment.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LncRNA MEG3, GAS5, and HOTTIP Polymorphisms Association with Risk of Polycystic Ovary Syndrome: A Case-Control Study and Computational Analyses.","authors":"Mahdi Majidpour, Saman Sargazi, Marzieh Ghasemi, Mahboobeh Sabeti Akbar-Abad, Mohammad Sarhadi, Ramin Saravani","doi":"10.1007/s10528-024-10977-1","DOIUrl":"https://doi.org/10.1007/s10528-024-10977-1","url":null,"abstract":"<p><p>As a multifactorial and endocrine disease, polycystic ovary syndrome (PCOS) affects approximately 5-20% of women worldwide. Recently, long noncoding RNAs (lncRNAs) have emerged as potent predictors of a particular phenotype in PCOS. Our preliminary study examines the link between polymorphisms in lncRNAs MEG3, HOTTIP, and GAS5 and the risk of PCOS. The present study included 200 women with PCOS and 200 healthy women. The studied variations were genotyped by applying the PCR-RFLP and the tetra-ARMS-PCR reaction) techniques. The effect of variation in lncRNA on miRNA:lncRNA interactions, lncRNA-RNA interaction network, and the impact of the variations on the splicing site were predicted using different computational databases. The codominant heterozygous (TC vs. TT) model, the dominant (TC + CC vs. TT) model, the overdominant (TT + CC vs. TC) model, the C allele of rs2023843, and the C allele of rs55829688 had a protective role against PCOS. The A allele of rs4081134 and G allele of rs7158663 of the MEG3 conferred an increased risk of PCOS by 1.37 and 1.44 folds, respectively. The interaction analysis revealed that TC/GG/AA/TC and TC/GG/GA/TC strongly decreased the risk of PCOS by 94 and 92%, respectively. Interestingly, MEG3 and HOTTIP variants can create or disrupt binding sites for several splicing factors. In our population, MEG3 rs4081134 and rs7158663, GAS5 rs55829688, and HOTTIP rs2023843 polymorphisms were associated with PCOS risk. Replication studies on larger sample sizes must be conducted to confirm these findings and investigate other potential causative factors involved in the pathophysiology of PCOS.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low Genetic Variation Among Trees in Cocoa Hand Pollination in the Offinso Municipality of Ghana Revealed by SSR Markers.","authors":"Daniel Dompreh, Pearl Kuranchie, Ruth Naa Ashiokai Prempeh, Acquah Emmanuel, Sevor Dora","doi":"10.1007/s10528-024-10978-0","DOIUrl":"https://doi.org/10.1007/s10528-024-10978-0","url":null,"abstract":"<p><p>Cocobod introduced nationwide artificial hand pollination in Ghana in 2017 to supplement natural pollination of Theobroma cacao L. (cocoa) by insects (Forcipomyia midges) to increase yield. Hybrid farms of 8-20 years old are mostly selected. Pollen donor and receiver trees are selected based on morphological characteristics. This study analyzed the genetic diversity among donor and recipient trees of cocoa hand pollination in three farms in the Offinso Municipality of Ghana using SSR markers. Twelve forward and reverse primer pairs out of fifteen primers screened were used to evaluate genetic intraspecific and interspecific diversity among 25 accessions based on clear amplification and reproducible scorable bands. A total of 115 polymorphic bands were detected which ranged between 5.00 and 17.00 with a mean of 9.58 alleles per locus. Cluster analysis showed similarity coefficient range of 0.10 to 0.83. Analysis of molecular variance (AMOVA) showed13% genetic variation between populations and 87% within populations of T. cacao. PhiPT value of 0.130 recorded showed weak genetic differentiation between populations. Gene diversity varied from 0.64 to 0.88 with primers MTcCIR33 and MTcCIR07 respectively. Highest observed heterozygosity (Ho) of 0.60 and least Polymorphism Information Content (PIC) of 0.57 were recorded. Pollen donor and recipient trees selected from the same or nearby farms accounts for present genetic structure of low genetic diversity between populations. Though hand pollination designs focus much on high yields, improving genetic diversity to prevent inbreeding in cocoa is recommended.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142708877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of circANKLE2 & circL3MBTL4 -RNAs Expression in Fertile and Infertile Men.","authors":"Randa El-Gamal, Adel Zalata, Shireen A Mazroa, Frank Comhaire, Ahmed Gamal, Olfat G Shaker, Noha M Hazem","doi":"10.1007/s10528-024-10963-7","DOIUrl":"https://doi.org/10.1007/s10528-024-10963-7","url":null,"abstract":"<p><p>There are many factors that affect male fertility such as chronic health problems, psychological factors, and illnesses. Male infertility can be caused abnormal sperm function, low sperm production or even blockages that prevent the delivery of sperm. The aim of the work is to determine the expression pattern of the circularANKLE2 and circularL3MBTL4 RNA in spermatozoa from fertile and infertile males, as well as the relationship between these circRNA transcripts and sperm quality. The study involved two groups: a control group comprising 40 healthy, fertile men and an experimental group of 90 infertile males. Semen samples were collected and processed for analysis using computer-assisted semen analysis. Following RNA extraction from sperm samples, reverse transcription and real-time PCR were performed to assess the levels of circular ANKLE2 and circular L3MBTL4 RNA. There was a significant up-regulation of circularANKLE2 RNA expression (p < 0.05), and a significant down-regulation of circularL3MBTL4 RNA expression (p < 0.05) in asthenozoospermia, astheno-teratozoospermia, and oligo-astheno-teratozoospermia groups, as well as, in immature spermatozoa separated from normozoospermic samples. Moreover, the altered expression of both circular L3MBTL4 and circular ANKLE2 RNA showed significant correlations with the associated sperm parameters. In conclusion, the expression of circular ANKLE2 RNA and circular L3MBTL4 RNA may play a significant role in male fertility and could serve as potential biomarkers of sperm quality, warranting further investigation for their application in infertility diagnostics.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142708861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Delving into the BURP Super family: A Comprehensive QTL-Assisted Study on RD22 genes and its Role in Salinity Stress Tolerance in Chickpea.","authors":"Sandhya Tripathi, Chellapilla Bharadwaj, Maloti Hembram, Neeraj Kumar, Aravind K Konda, B Mondal, N C Gupta, G P Dixit, K R Soren","doi":"10.1007/s10528-024-10955-7","DOIUrl":"https://doi.org/10.1007/s10528-024-10955-7","url":null,"abstract":"<p><p>DNA polymorphisms QTL analysis in crops is a valuable tool to study the genetic basis of complex traits in agricultural plants. Candidate gene for abiotic (salinity) stress was spotted in the QTL region spanning CaLG03 and CaLG06 in our previous study. In continuity to the same, we have picked up QTL-associated Cicer arietinum RD22 (CaRD22) gene which belongs to BURP-domain-containing group of proteins (BURPs) and studied its expression patterns in salinity-tolerant (ICCV10) and susceptible (DCP92-3) genotypes of chickpea. Earlier, few systematic categorizations of BURPs including RD22 gene were reported, but no QTL driven functional prediction w.r.t salinity stress is known so far. Here, a couple of in silico approaches were utilized followed by lab validation to speculate the features of RD22 BURP gene particularly Ca_23903 in Chickpea. A complete set of fifteen BURP genes located on chromosome 2, 4, 5, 6, 7, 8, and Scaffold 653 were studied. Motif analysis, gene structure study, phylogenetic analysis, cis-element analysis in promoter regions, and co-expression network analysis were performed in addition to the quantitative expression analysis. Expression profiling of RD22 gene and other interacting gene partners were performed in root and shoot tissues exposed to salt stress (200 mM). The findings predict the behavior of BURP genes specifically RD22 subtype during salinity conditions emphasizing their implications in associated physiological processes.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The CD40/CD40L Pathway Regulates the Aggressiveness of Ovarian Cancer Cells via the Activation of Regulatory B Cells.","authors":"Shanshan Ma, Pengfei Chen, Suyang Guo, Liangliang Wang, Jialin Hu, Junjun Shao","doi":"10.1007/s10528-024-10945-9","DOIUrl":"https://doi.org/10.1007/s10528-024-10945-9","url":null,"abstract":"<p><p>Ovarian cancer (OC) is a challenging cancer frequently detected at advanced stages. Regulatory B cells (Breg cells) can impair antitumor immunity in patients with OC. The imbalanced serum soluble CD40/CD40L pathway is associated with ovarian tumors. This study aimed to explore the mechanisms involving CD40/CD40L signaling through which Breg cells promote the progression of OC. Breg cells were isolated from peripheral blood samples of 20 patients with OC and 20 healthy controls and identified by flow cytometry. Then, the soluble CD40L concentration in peripheral blood serum of OC patients and healthy volunteers was measured by enzyme-linked immunosorbent assay (ELISA), and we found that the serum soluble CD40L level markedly increased and the proportion of Breg cells was positively correlated with CD40L level in peripheral blood of OC patients. Besides, Breg cells were isolated from spleens of female C57BL/6 WT mice and CD40^-/- mice. Reverse transcription-quantitative polymerase chain reaction, cell counting kit-8 assays, colony formation assays, flow cytometry, Western blotting, wound healing assays, and Transwell assays were conducted to assess the in vitro effect of Breg cells and CD40. We found that Breg cells contributed to cell proliferation, migration, and invasion and suppressed cell apoptosis in OC via the CD40/CD40L pathway. Moreover, we established a xenograft tumor model in female nude BALB/c mice. Tumor size and weight were evaluated, and Western blotting and ELISA were conducted, and we found that Breg cells promoted tumor growth via CD40 signaling. In conclusion, this study demonstrates that Breg cells activated by the CD40/CD40L pathway promotes the aggressiveness of OC cells and tumor growth, indicating that targeting the CD40/CD40L pathway might represent a novel therapeutic option for OC treatment.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142685717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FENDRR represses Bladder Cancer Cell Proliferation, Stemness, Migration, Invasion, and EMT Process by Targeting miR-18a-5p/AFF4 Axis.","authors":"Changyuan Dai, Qingwen Li, Lili Wang, Jiajun Zhang, Shuai Yang, Xiaole Zhang","doi":"10.1007/s10528-024-10944-w","DOIUrl":"10.1007/s10528-024-10944-w","url":null,"abstract":"<p><p>Bladder cancer (BC) is the most prevalent malignancy of the urinary tract and ranks among the most common tumors globally due to its high recurrence and fatality rates. Evidence suggests that long noncoding RNAs (lncRNAs) may serve as novel biomarkers for cancer therapy. The study aimed to investigate the functions of lncRNA fetal-lethal non-coding developmental regulatory RNA (FENDRR) in regulating malignant phenotypes of BC cell lines (T24 and RT-4) and the underlying mechanism. RT-qPCR was used to measure FENDRR, miR-18a-5p, and AF4/FMR2 family member 4 (AFF4) expression in BC tissue samples and cell lines. Subcellular fractionation assay and fluorescence in situ hybridization were conducted to determine the localization of FENDRR in T24 and RT-4 cell. EdU, sphere formation, Transwell invasion, and wound healing assays were carried out to detect the changes in BC cell proliferation, stemness, invasion, and migration in response to FENDRR or AFF4 dysregulation. Protein levels of epithelial-mesenchymal transition (EMT) markers were quantified by western blotting. The interaction between miR-18a-5p and FENDRR (or AFF4) was verified by luciferase reporter assays. Experimental results revealed that FENDRR expression was downregulated in BC tissue samples and cell lines, with primary localization in cytoplasm of T24 and RT-4 cells. FENDRR overexpression inhibited BC cell proliferation, migration, invasion, stemness, and EMT process. FENDRR was shown to bind with miR-18a-5p, and AFF4 is a direct target of miR-18a-5p. In addition, AFF4 knockdown partially counteracted the effect of FENDRR on malignant phenotypes of BC cells. In summary, FENDRR represses BC cell proliferation, migration, invasion, stemness, and EMT process by targeting the miR-18a-5p/AFF4 axis.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142685716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gastrodin Attenuates Neuroinflammation and Injury in Young Rats with LiCl/Pilocarpine-Induced Status Epilepticus.","authors":"Jie Dai, Hai-Lin Shen, Jia Li, Yong Zhou, Zheng-Xie Dong, Xiang-Yang Zhu","doi":"10.1007/s10528-024-10971-7","DOIUrl":"https://doi.org/10.1007/s10528-024-10971-7","url":null,"abstract":"<p><p>Status epilepticus is a severe neurological emergency that often leads to long-term neuronal damage and functional impairment. Gastrodin is a compound widely used in traditional Chinese medicine with potential neuroprotective effects. This study aims to investigate the effects of GAS on neuroinflammation and injury caused by LiCl/pilocarpine-induced SE in young rats. SE in rats was induced using the LiCl/pilocarpine model. Morris water maze and Y-maze experiments were used for the behavioral test of rats. Enzyme-linked immunosorbent assay was utilized to quantify the levels of interleukin (IL)-1β, IL-6, and IL-8 levels, and biochemical kits assessed the levels of malondialdehyde, superoxide dismutase and glutathione peroxidase (GSH-px) in hippocampus tissues. Additionally, Western blot analysis was performed to evaluate the protein expression levels of p-p65, p65, p-IκBα and IκBα, which are key factors of the nuclear factor kappa B (NF-κB) signaling pathway. Compared to the control group, the SE group rats exhibited reduced learning and memory abilities. Markedly elevated levels of inflammatory factors (IL-1β, IL-6, and IL-8). The expression levels of p-p65 and p-IκBα were significantly upregulated, while IκBα levels were notably decreased. Following GAS treatment, the latency of seizure onset was significantly shortened, the incidence of SE was significantly reduced and the severity of nerve injury was alleviated. Additionally, both the inflammation levels and the oxidative stress were significantly decreased, primarily through inhibition NF-κB signaling pathway. These findings suggest that GAS may be a potential therapeutic agent for treating SE.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distribution of High-Risk Human Papillomavirus in Self-Collected Cervicalvaginal Samples from the General Malian Population.","authors":"Bakarou Kamate, Yaya Kassogue, Brehima Diakite, Ban Traore, Kadidiatou Cisse, Fousseyni Diarra, Oumar Kassogue, Modibo Diarra, Aissata Coulibaly, Bourama Coulibaly, Aminata Maiga, Madani Ly, Hama Diallo, Sidi Boula Sissoko, Adama Seydou Sissoko, Cheick Bougadari Traore, Ibrahima Teguete, Sekou Bah, Guimogo Dolo, Demirkan Besim Gursel, Jane Holl, Lifang Hou, Mamoudou Maiga","doi":"10.1007/s10528-024-10949-5","DOIUrl":"https://doi.org/10.1007/s10528-024-10949-5","url":null,"abstract":"<p><p>Cervical cancer (CC) remains a real public health problem in low- and middle-income countries, where technical resources and competent personnel are insufficient. Persistent cervix infection by high-risk human papillomavirus (Hr-HPV) is the main cause of CC development. In the current study, we examined the distribution of Hr-HPV in the general healthy Malian population using cervicovaginal self- sampling. A total of 354 women were recruited, with a median age of 34 ± 11.37 years, IQR (27-43). We found that 100% of participants agreed to self-sample at the health center. For result announcement 99.2% expressed their preference to be contacted by cell phone. Furthermore, 100% of study participants showed their willingness to undergo confirmatory CC test in case of Hr-HPV test proved positive, and to receive treatment in the event of the presence of cervical lesions. The overall prevalence of Hr-HPV was 21.2% (95% CI: 17-25.8). HPV31/35/33/52/58 with 11.9% (95% CI: 8.7-15.7) and HPV39/68/56/66 with 5.9% (95% CI: 3.7-8.9) were the most common Hr-HPV subtypes. We noted that Hr-HPV genotypes were more prevalent among women under 25 years, 36.1% (N = 61). In addition, the distribution of Hr-HPV was statistically associated with age, W = 12,374, p = 0.015. Our data showed that 25.3% (N = 19) of Hr-HPV-positive women were tested positive by VIA/VILI. Among the 19 VIA/VILI-positive women, histological examination showed that 4 were CIN1, 4 were CIN2, and 2 were CIN3 grades. In addition, the median age of participants with CIN2 and CIN3 was statistically higher than the median of those with CIN1 grade, 25 years IQR (21-26.75) versus 50 years, IQR (40.25-55), W = 24, p = 0.009. In sum, end-users are very satisfied with the cervicovaginal self-sampling device for identifying HR-HPV genotypes as part of CC screening. In addition, it enables hospital practitioners to take the necessary action after triaging women according to their HR-HPV genotype.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Novel Direct AR Target Gene Annexin A2 Mediates Androgen-Induced Cellular Senescence in Prostate Cancer Cells.","authors":"Kimia Mirzakhani, Mehdi Heidari Horestani, Julia Kallenbach, Golnaz Atri Roozbahani, Aria Baniahmad","doi":"10.1007/s10528-024-10953-9","DOIUrl":"https://doi.org/10.1007/s10528-024-10953-9","url":null,"abstract":"<p><p>Clinical trials for prostate cancer (PCa) patients have implemented the bipolar androgen therapy (BAT) that includes the treatment with supraphysiological androgen level (SAL). SAL treatment induces cellular senescence in tumor samples of PCa patients and in various PCa cell lines, including castration-resistant PCa (CRPC), and is associated with enhanced phospho-AKT levels. Using an AKT inhibitor (AKTi), the SAL-mediated cell senescence is inhibited. Here, we show by RNA-seq analyses of two human PCa cell lines, that annexin A2 (ANXA2) expression is induced by SAL and repressed by co-treatment with AKTi. Higher ANXA2 expression is associated with better survival of PCa patients and suggests that ANXA2 is part of SAL-mediated tumor suppressive activity. ChIP-seq revealed that AR is recruited to the intronic regions of ANXA2 gene suggesting that ANXA2 is a novel direct AR target gene. Knockdown of ANXA2 shows that SAL-induced cellular senescence is mediated by ANXA2 and enhances the levels of phospho-AKT indicating an interaction between the AR, ANXA2 and AKT. Notably, we found that the level of heat shock protein HSP27, known to interact with ANXA2, is associated with cellular senescence. HSP27 level is induced by SAL but the induction is blunted by knockdown of ANXA2 suggesting a novel ANXA2-HSP27 pathway in PCa. This was confirmed using an HSP27 inhibitor that reduced the SAL-induced cellular senescence levels suggesting that ANXA2 upregulates HSP27 to mediate AR-signaling in SAL-induced cellular senescence. Thus, the data indicate ANXA2-HSP27 cross-talk as novel factors in the signaling by the AR-AKT pathway to mediate cellular senescence.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}