BMC Molecular and Cell Biology最新文献

{"title":"RUNX3 mediates keloid fibroblast proliferation through deacetylation of EZH2 by SIRT1.","authors":"Hanye Liu,&nbsp;Guanghai Yan,&nbsp;Li Li,&nbsp;Dandan Wang,&nbsp;Yu Wang,&nbsp;Shan Jin,&nbsp;Zhehu Jin,&nbsp;Liangchang Li,&nbsp;Lianhua Zhu","doi":"10.1186/s12860-022-00451-4","DOIUrl":"https://doi.org/10.1186/s12860-022-00451-4","url":null,"abstract":"<p><strong>Background: </strong>Keloid is a benign proliferative fibrous disease featured by excessive fibroblast proliferation after skin injury. However, the mechanism of abnormal cell proliferation is still unclear. Herein, we investigated the mechanism of abnormal proliferation in keloids involving Sirtuin 1(SIRT1)/ Zeste Homolog 2 (EZH2)/ Runt-related transcription factor 3 (RUNX3).  METHODS: HE staining was used to observe the histopathological changes. Western blot was performed to detect SIRT1/EZH2/RUNX3 and cell cycle related proteins. RT-PCR detected EZH2 mRNA. After knockdown of EZH2 or overexpression of RUNX3, cell proliferation and cell cycle was analyzed. Immunoprecipitation was used to detect acetylated EZH2.</p><p><strong>Results: </strong>The results showed that overexpression of RUNX3 inhibited cell proliferation and arrested cell cycle at G1/S phase, whereas inhibition of SIRT1 promoted cell proliferation and G1/S phase of the cell cycle. Knockdown of EZH2 promoted the expression of RUNX3, inhibited cell proliferation and shortened the progression of G1 to S phase. Simultaneous knockdown of EZH2 and inhibition of SIRT1 reversed these effects. Inhibition of SIRT1 increased its protein stability by increasing EZH2 acetylation, thereby reducing the expression of RUNX3 and promoting cell proliferation.</p><p><strong>Conclusions: </strong>Conclusively, the SIRT1/EZH2/RUNX3 axis may be an important pathway in the regulation of abnormal proliferation in keloids.</p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":"23 1","pages":"52"},"PeriodicalIF":2.8,"publicationDate":"2022-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9730640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10693986","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}

{"title":"CARD9 contributes to ovarian cancer cell proliferation, cycle arrest, and cisplatin sensitivity.","authors":"Yanming Wang,&nbsp;Chao Wang,&nbsp;Yan Zhu","doi":"10.1186/s12860-022-00447-0","DOIUrl":"https://doi.org/10.1186/s12860-022-00447-0","url":null,"abstract":"<p><strong>Background: </strong>Ovarian cancer recurrence and chemotherapy resistance are still urgent issues, and exploring the mechanisms of metastasis and chemotherapy resistance is beneficial to the development of therapeutic methods. Caspase recruitment domain family member 9 (CARD9) and homeobox B5 (HOXB5) are related and both are upregulated in ovarian cancer. This study aimed to define their functions in ovarian cancer cell proliferation, migration, and cisplatin sensitivity.</p><p><strong>Results: </strong>The levels of CARD9 were detected in acquired ovarian cancer tissues and cell lines. CARD9 was indeed abnormally upregulated in them. CARD9 knockdown significantly suppressed cell proliferation, colony formation, migration, cycle arrest, and cisplatin sensitivity. HOXB5 bound to the CARD9 promoter, and HOXB5 overexpression reversed the regulation by CARD9 knockdown in cells, as well as the activation of NF-κB signaling. This indicated that CARD9 was positively regulated by HOXB5 in ovarian cancer cells.</p><p><strong>Conclusion: </strong>Together, CARD9 is involved in ovarian cancer cell proliferation, migration, and cisplatin sensitivity via NF-κB signaling after transcriptional activation by HOXB5.</p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":"23 1","pages":"49"},"PeriodicalIF":2.8,"publicationDate":"2022-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9703781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10320729","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}

{"title":"RNAP II produces capped 18S and 25S ribosomal RNAs resistant to 5′-monophosphate dependent processive 5′ to 3′ exonuclease in polymerase switched Saccharomyces cerevisiae","authors":"Miguel A. Rocha, B. S. Gowda, J. Fleischmann","doi":"10.1186/s12860-022-00417-6","DOIUrl":"https://doi.org/10.1186/s12860-022-00417-6","url":null,"abstract":"","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":"23 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2022-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65674640","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}

{"title":"High miRNA-378 expression has high diagnostic values for pulmonary tuberculosis and predicts adverse outcomes.","authors":"Xiaolu Sun, Kai Liu, Yan Zhao, Tianhua Zhang","doi":"10.1186/s12860-022-00413-w","DOIUrl":"https://doi.org/10.1186/s12860-022-00413-w","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary tuberculosis (TB) is a chronic infectious disease. microRNA (miR)-378 is involved in TB diagnosis. This study explored the effects of miR-378 on TB patients.</p><p><strong>Methods: </strong>A total of 126 TB patients were selected, including 63 active TB and 63 latent TB, with 62 healthy subjects as controls. Serum miR-378 expression was detected. The diagnostic value of miR-378 in TB was analyzed using the ROC curve. Immune inflammatory factor levels were detected and their correlations with miR-378 expression were analyzed. The drug resistance of active TB patients was recorded after standard treatment. miR-378 expression in drug-resistant TB patients was detected. The effects of miR-378 on adverse outcome incidence were analyzed.</p><p><strong>Results: </strong>miR-378 expression was highly expressed in TB and the expression was higher in the active group than the latent group. Serum miR-378 expression > 1.490 had high sensitivity and specificity in TB diagnosis. miR-378 expression was correlated with TB clinical indexes. IL-4, IL-6, and IL-1β levels were highly expressed, while IFN-γ, TNF-α, and IL-12 levels were lowly expressed in TB patients. Serum miR-378 level in the active group was positively correlated with serum IL-4, IL-6, and IL-1β, and negatively correlated with serum IFN-γ, TNF-α, and IL-12 concentrations. miR-378 expression was downregulated in the TB treated, single (SDR TB) and multi-drug resistance (MDR TB) groups, the miR-378 expression in SDR TB and MDR TB groups was higher than the TB treated group and lower in the SDR TB group than the MDR TB group. High miR-378 expression predicted higher adverse outcome incidence.</p><p><strong>Conclusions: </strong>High miR-378 expression assisted TB diagnosis and predicted adverse outcomes.</p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":"23 1","pages":"14"},"PeriodicalIF":2.4,"publicationDate":"2022-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8934448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046336","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}

{"title":"Correction to: Influence of mechanical and TGF-β3 stimulation on the tenogenic differentiation of tonsil-derived mesenchymal stem cells.","authors":"Jaeyeon Wee,&nbsp;Hyang Kim,&nbsp;Sang-Jin Shin,&nbsp;Taeyong Lee,&nbsp;Seung Yeol Lee","doi":"10.1186/s12860-022-00406-9","DOIUrl":"https://doi.org/10.1186/s12860-022-00406-9","url":null,"abstract":"","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":"23 1","pages":"7"},"PeriodicalIF":2.8,"publicationDate":"2022-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8796344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10263985","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}

{"title":"Correction to: A potential implication of UDP-glucuronosyltransferase 2B10 in the detoxification of drugs used in pediatric hematopoietic stem cell transplantation setting: an in silico investigation.","authors":"Shannon Robin,&nbsp;Khalil Ben Hassine,&nbsp;Jayaraman Muthukumaran,&nbsp;Simona Jurkovic Mlakar,&nbsp;Maja Krajinovic,&nbsp;Tiago Nava,&nbsp;Chakradhara Rao S Uppugunduri,&nbsp;Marc Ansari","doi":"10.1186/s12860-022-00407-8","DOIUrl":"https://doi.org/10.1186/s12860-022-00407-8","url":null,"abstract":"","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":"23 1","pages":"6"},"PeriodicalIF":2.8,"publicationDate":"2022-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8793165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10630528","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}

{"title":"A computational model of mutual antagonism in the mechano-signaling network of RhoA and nitric oxide.","authors":"Akila Surendran,&nbsp;C Forbes Dewey,&nbsp;Boon Chuan Low,&nbsp;Lisa Tucker-Kellogg","doi":"10.1186/s12860-021-00383-5","DOIUrl":"https://doi.org/10.1186/s12860-021-00383-5","url":null,"abstract":"<p><strong>Background: </strong>RhoA is a master regulator of cytoskeletal contractility, while nitric oxide (NO) is a master regulator of relaxation, e.g., vasodilation. There are multiple forms of cross-talk between the RhoA/ROCK pathway and the eNOS/NO/cGMP pathway, but previous work has not studied their interplay at a systems level. Literature review suggests that the majority of their cross-talk interactions are antagonistic, which motivates us to ask whether the RhoA and NO pathways exhibit mutual antagonism in vitro, and if so, to seek the theoretical implications of their mutual antagonism.</p><p><strong>Results: </strong>Experiments found mutual antagonism between RhoA and NO in epithelial cells. Since mutual antagonism is a common motif for bistability, we sought to explore through theoretical simulations whether the RhoA-NO network is capable of bistability. Qualitative modeling showed that there are parameters that can cause bistable switching in the RhoA-NO network, and that the robustness of the bistability would be increased by positive feedback between RhoA and mechanical tension.</p><p><strong>Conclusions: </strong>We conclude that the RhoA-NO bistability is robust enough in silico to warrant the investment of further experimental testing. Tension-dependent bistability has the potential to create sharp concentration gradients, which could contribute to the localization and self-organization of signaling domains during cytoskeletal remodeling and cell migration.</p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":"22 Suppl 1","pages":"47"},"PeriodicalIF":2.8,"publicationDate":"2021-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8507106/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39506686","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}

{"title":"MDMX is essential for the regulation of p53 protein levels in the absence of a functional MDM2 C-terminal tail.","authors":"Jack D Sanford, Jing Yang, Jing Han, Laura A Tollini, Aiwen Jin, Yanping Zhang","doi":"10.1186/s12860-021-00385-3","DOIUrl":"10.1186/s12860-021-00385-3","url":null,"abstract":"<p><strong>Background: </strong>MDM2 is an E3 ubiquitin ligase that is able to ubiquitinate p53, targeting it for proteasomal degradation. Its homologue MDMX does not have innate E3 activity, but is able to dimerize with MDM2. Although mouse models have demonstrated both MDM2 and MDMX are individually essential for p53 regulation, the significance of MDM2-MDMX heterodimerization is only partially understood and sometimes controversial. MDM2^C462A mice, where the C462A mutation abolishes MDM2 E3 ligase activity as well as its ability to dimerize with MDMX, die during embryogenesis. In contrast, the MDM2^Y487A mice, where the Y487A mutation at MDM2 C-terminus significantly reduces its E3 ligase activity without disrupting MDM2-MDMX binding, survive normally even though p53 is expressed to high levels. This indicates that the MDM2-MDMX heterodimerization plays a critical role in the regulation of p53. However, it remains unclear whether MDMX is essential for the regulation of p53 protein levels in the context of an endogenous MDM2 C-terminal tail mutation.</p><p><strong>Results: </strong>Here, we studied the significance of MDM2-MDMX binding in an MDM2 E3 ligase deficient context using the MDM2^Y487A mouse embryonic fibroblast (MEF) cells. Surprisingly, down-regulation of MDMX in MDM2^Y487A MEFs resulted in a significant increase of p53 protein levels. Conversely, ectopic overexpression of MDMX reduced p53 protein levels in MDM2^Y487A MEFs. Mutations of the RING domain of MDMX prevented MDMX-MDM2 binding, and ablated MDMX-mediated suppression of p53 protein expression. Additionally, DNA damage treatment and nuclear sequestration of MDMX inhibited MDMX activity to suppress p53 protein expression.</p><p><strong>Conclusions: </strong>These results suggest that MDMX plays a key role in suppressing p53 protein expression in the absence of normal MDM2 E3 ligase activity. We found that the ability of MDMX to suppress p53 levels requires MDM2 binding and its cytoplasmic localization, and this ability is abrogated by DNA damage. Hence, MDMX is essential for the regulation of p53 protein levels in the context of an MDM2 C-terminal mutation that disrupts its E3 ligase activity but not MDMX binding. Our study is the first to examine the role of MDMX in the regulation of p53 in the context of endogenous MDM2 C-terminal mutant MEF cells.</p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":"22 1","pages":"46"},"PeriodicalIF":2.8,"publicationDate":"2021-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8459461/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9352209","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}

{"title":"Ommochrome pathway genes kynurenine 3-hydroxylase and cardinal participate in eye pigmentation in Plutella xylostella.","authors":"Xuejiao Xu,&nbsp;Tim Harvey-Samuel,&nbsp;Jie Yang,&nbsp;Luke Alphey,&nbsp;Minsheng You","doi":"10.1186/s12860-020-00308-8","DOIUrl":"https://doi.org/10.1186/s12860-020-00308-8","url":null,"abstract":"<p><strong>Background: </strong>Eye pigmentation genes have been utilized as visible markers for constructing genetic control prototypes in several insect vectors of human disease. Here, orthologs of two ommochrome pathway genes, kynurenine 3-hydroxylase (kmo) and cardinal, were investigated in Plutella xylostella, a globally distributed, economically important pest of Brassica crops.</p><p><strong>Results: </strong>Both somatic mosaic and germline mutations were efficiently created using the CRISPR/Cas9 system, and null mutant strains of Pxkmo and Pxcardinal were obtained. A frame-shift mutation in Pxkmo caused yellow compound eyes at adult stage while an in-frame mutation lacking two amino acids resulted in a hypomorphic red eye phenotypes. In contrast, Pxcardinal-deficient moths with a frame-shift mutation exhibited yellow eye pigmentation in newly emerged adults which turned to red as the adults aged. Additionally, differences were observed in the coloration of larval ocelli, brains and testes in Pxkmo and Pxcardinal yellow-eye mutant lines.</p><p><strong>Conclusions: </strong>Our work identifies the important roles of Pxkmo and Pxcardinal in P. xylostella eye pigmentation and provides tools for future genetic manipulation of this important crop pest.</p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":"21 1","pages":"63"},"PeriodicalIF":2.8,"publicationDate":"2020-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12860-020-00308-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9085915","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}

{"title":"STAU2 protein level is controlled by caspases and the CHK1 pathway and regulates cell cycle progression in the non-transformed hTERT-RPE1 cells","authors":"L. Condé, Yulemi Gonzalez Quesada, Florence Bonnet-Magnaval, R. Beaujois, L. DesGroseillers","doi":"10.21203/rs.3.rs-60003/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-60003/v1","url":null,"abstract":"Background Staufen2 (STAU2) is an RNA binding protein involved in the posttranscriptional regulation of gene expression. In neurons, STAU2 is required to maintain the balance between differentiation and proliferation of neural stem cells through asymmetric cell division. However, the importance of controlling STAU2 expression for cell cycle progression is not clear in non-neuronal dividing cells. We recently showed that STAU2 transcription is inhibited in response to DNA-damage due to E2F1 displacement from the STAU2 gene promoter. We now study the regulation of STAU2 steady-state levels in unstressed cells and its consequence for cell proliferation. Results CRISPR/Cas9-mediated and RNAi-dependent STAU2 depletion in the non-transformed hTERT-RPE1 cells both facilitate cell proliferation suggesting that STAU2 expression influences pathway(s) linked to cell cycle controls. Such effects are not observed in the CRISPR STAU2-KO cancer HCT116 cells nor in the STAU2-RNAi-depleted HeLa cells. Interestingly, a physiological decrease in the steady-state level of STAU2 is controlled by caspases. This effect of peptidases is counterbalanced by the activity of the CHK1 pathway suggesting that STAU2 partial degradation/stabilization fines tune cell cycle progression in unstressed cells. A large-scale proteomic analysis using STAU2/biotinylase fusion protein identifies known STAU2 interactors involved in RNA translation, localization, splicing, or decay confirming the role of STAU2 in the posttranscriptional regulation of gene expression. In addition, several proteins found in the nucleolus, including proteins of the ribosome biogenesis pathway and of the DNA damage response, are found in close proximity to STAU2. Strikingly, many of these proteins are linked to the kinase CHK1 pathway, reinforcing the link between STAU2 functions and the CHK1 pathway. Indeed, inhibition of the CHK1 pathway for 4 h dissociates STAU2 from proteins involved in translation and RNA metabolism. Conclusions These results indicate that STAU2 is involved in pathway(s) that control(s) cell proliferation, likely via mechanisms of posttranscriptional regulation, ribonucleoprotein complex assembly, genome integrity and/or checkpoint controls. The mechanism by which STAU2 regulates cell growth likely involves caspases and the kinase CHK1 pathway.","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":"22 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2020-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49630935","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}