Yingying Guo, Panpan Zhang, Zhixing Gao, Xiaotian Liu, Chen Su, Su Chen, Tao An, Jingjing Hou
{"title":"Inhibition of USP22 by miR-200b-5p represses gastric cancer cell proliferation and migration by targeting the NF-κB signaling pathway.","authors":"Yingying Guo, Panpan Zhang, Zhixing Gao, Xiaotian Liu, Chen Su, Su Chen, Tao An, Jingjing Hou","doi":"10.3724/abbs.2024231","DOIUrl":"https://doi.org/10.3724/abbs.2024231","url":null,"abstract":"<p><p>Gastric cancer (GC) is an aggressive tumor type with an intricate pathogenesis and limited therapeutic options. Ubiquitin-specific protease 22 (USP22) is a protein implicated in cell proliferation, metastasis, and tumorigenesis. However, the regulatory mechanisms governing USP22 in GC are still not fully understood. In this study, we perform bioinformatics analysis to identify conserved miRNA recognition sites for miR-200b-5p within the 3'UTR of <i>USP22</i>. Validation via luciferase reporter assay confirms the transcriptional regulation of <i>USP22</i> by miR-200b-5p. Overexpression of miR-200b-5p markedly inhibits the proliferation and migration of GC cells <i>in vitro</i> and suppresses tumor growth <i>in vivo</i>. Conversely, ectopic expression of USP22 reversed this effect by modulating the NF-κB signaling pathway. Additionally, qPCR analysis reveals an inverse correlation between the miR-200b-5p level and USP22 expression in GC. Collectively, our findings indicate that miR-200b-5p-mediated inhibition of USP22 attenuates cell proliferation by targeting the NF-κB signaling pathway in GC, suggesting that miR-200b-5p and USP22 could serve as potential diagnostic or therapeutic targets for gastric cancer and other related human diseases.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142875725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zengli Zhou, Shufang Ye, Jingyu Chen, Fei Dai, Luyi Chen, Ran Ye, Jianmei Zhang, Gefei Chen, Yanjiao Wang, Yangyang Liu
{"title":"ATF4 promotes glutaminolysis and glycolysis in colorectal cancer by transcriptionally inducing SLC1A5.","authors":"Zengli Zhou, Shufang Ye, Jingyu Chen, Fei Dai, Luyi Chen, Ran Ye, Jianmei Zhang, Gefei Chen, Yanjiao Wang, Yangyang Liu","doi":"10.3724/abbs.2024226","DOIUrl":"https://doi.org/10.3724/abbs.2024226","url":null,"abstract":"<p><p>Glutaminolysis and glycolysis promote the malignant progression of colorectal cancer. The role of activating transcription factor 4 (ATF4) in solute carrier family 1 member 5 (SLC1A5)-mediated glutaminolysis and glycolysis remains to be elucidated. SLC1A5 and ATF4 expression levels are detected in colorectal cancer tissues. <i>ATF4</i> is knocked down or overexpressed to assess its role in cell viability, migration and invasion. <i>SLC1A5</i> is knocked down to evaluate its role in cell viability, migration, invasion, and metastasis and the metabolism of glutamine and glucose. The regulatory effect of the transcription factor ATF4 on SLC1A5 transcription and expression is determined using a luciferase reporter assay and chromatin immunoprecipitation (ChIP) techniques. Upregulated ATF4 and SLC1A5 expressions are observed in tumor tissue, which is positively correlated with the tumor, node, and metastasis (TNM) stages. <i>ATF4-</i>overexpressing SW480 cells show the increased cell viability, migration and invasion. Conversely, <i>ATF4</i> knockdown decreases the viability, migration and invasion of HCT-116 cells. <i>SLC1A5</i> knockdown inhibits viability, migration, invasion, and metastasis and the metabolism of glutamine and glucose in HT-29 cells, as well as the expressions of two key glycolytic enzymes, hexokinase 2 (HK2) and pyruvate kinase M2 (PKM2). The luciferase activity of the <i>SLC1A5</i> promoter is increased by <i>ATF4</i> overexpression. <i>SLC1A5</i> promoter enrichment is increased by anti-ATF4 antibody immunoprecipitation in <i>ATF4</i>-overexpressing colorectal cells, indicating that ATF4 targets SLC1A5 to promote glutamine and glucose metabolism in these cells. In summary, the ATF4/SLC1A5 axis plays a significant role in the progression of colorectal cancer by regulating glutamine metabolism and glycolysis.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142851958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wangwen Wang, Xi Lu, Chengjun Zhu, Jie Li, Yue Liu, Zhangchao Yao, Xiaolin Li
{"title":"O-GlcNAcylation-related genes mediate tumor microenvironment characteristics and prediction of immunotherapy response in gastric cancer.","authors":"Wangwen Wang, Xi Lu, Chengjun Zhu, Jie Li, Yue Liu, Zhangchao Yao, Xiaolin Li","doi":"10.3724/abbs.2024222","DOIUrl":"https://doi.org/10.3724/abbs.2024222","url":null,"abstract":"<p><p>We aim to identify molecular clusters related to O-GlcNAcylation and establish a novel scoring system for predicting prognosis and immunotherapy efficacy in patients with gastric cancer (GC). The transcriptomic and clinical data are obtained from XENA-UCSC and GEO databases. The O-GlcNAcylation-related genes are obtained from the GSEA database. Consensus clustering analysis is employed to identify O-GlcNAcylation-related molecular clusters, and principal component analysis (PCA) is utilized to develop a novel prognostic scoring system for predicting GC outcomes and immunotherapy efficacy. The prognostic accuracy of the scoring system is assessed across five real-world cohorts. The biological function of actin alpha 2, smooth muscle (ACTA2) in GC is determined through experimental verification. Using 34 O-GlcNAcylation-related genes associated with prognosis in GC patients, these individuals are divided into two distinct subgroups characterized by different outcomes, tumor microenvironment profiles, and clinical case characteristics. The DEGs between the two subgroups are subsequently used to further divide the GC patients into two subgroups by consensus cluster analysis. PCA is used to construct a prognostic scoring system, which reveal that patients in the low-score subgroup have a better prognosis and greater benefit from immunotherapy. The accuracy of the scoring system is confirmed through validation in a cohort of patients receiving immunotherapy in the real world. ACTA2 promotes proliferation and inhibits apoptosis in GC cells. These findings suggest that we successfully establish molecular clusters associated with O-GlcNAcylation and develop a scoring system that demonstrates strong performance in predicting the prognosis of patients with GC and the effect of immunotherapy interventions.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142852020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Baocai Liu, Yadong Zhang, Quan Wang, Qian Wang, Zhixin Wang, Li Feng
{"title":"CD40 ligation-induced ERK activation leads to enhanced radiosensitivity in cervical carcinoma cells via promoting autophagy.","authors":"Baocai Liu, Yadong Zhang, Quan Wang, Qian Wang, Zhixin Wang, Li Feng","doi":"10.3724/abbs.2024229","DOIUrl":"https://doi.org/10.3724/abbs.2024229","url":null,"abstract":"<p><p>CD40, a member of the tumor necrosis factor (TNF) receptor superfamily, plays an important role not only in the immune system but also in tumor progression. CD40 ligation reportedly promotes autophagy in immune cells. However, the effects of CD40 ligation on autophagy and its mechanism in solid tumor cells are still unclear. In this study, we find that CD40 ligation promotes autophagosome formation and consequently promotes autophagic flux in cervical cancer cells. Mechanistically, this effect relies on ERK contributing to CD40 ligation-induced ATG13 upregulation by p53. Furthermore, we demonstrate that CD40 ligation-induced autophagy increases the radiosensitivity of cervical cancer cells. Taken together, our results provide new evidence for the involvement of the CD40 pathway in autophagy and radiotherapy in cervical cancer cells.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142852018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yi Mao, Hongtao Li, Gang Xu, Jiazhen Tian, Yuechan Chen, Zhiwei Zhang
{"title":"Alpha-lipoic acid targets <i>KLF7</i> expression to inhibit cervical cancer progression.","authors":"Yi Mao, Hongtao Li, Gang Xu, Jiazhen Tian, Yuechan Chen, Zhiwei Zhang","doi":"10.3724/abbs.2024212","DOIUrl":"https://doi.org/10.3724/abbs.2024212","url":null,"abstract":"<p><p>It is unclear what part KLF7 plays in cervical cancer. In this study, immunohistochemical and bioinformatics analyses reveal that KLF7 expression is lower in normal cervical tissues than in cervical cancer tissues ( <i>P</i>≤0.05), and the high level of <i>KLF7</i> transcripts in cervical cancer tissues is negatively correlated with patients' overall and disease-free survival ( <i>P</i><0.05). In addition, KLF7 overexpression facilitates the proliferation, migration, and invasion of cervical cells, reduces PFKL expression, and increases the expressions of <i>KLF4</i>, <i>Nanog</i>, <i>OCT4</i>, <i>CD44</i>, <i>SOX2</i>, and <i>ACADL</i> ( <i>P</i><0.05). Additionally, knocking out the Exon 2 of <i>KLF7</i> in HeLa cells results in a decrease in the total expression of KLF7 but an increase in the nuclear expression of KLF7, an increase in the capacity for proliferation, migration, invasion, and oncogenicity ( <i>P</i><0.05), and an increase in the density and ridge density of mitochondria. Consistent with these findings, RNA-seq analysis shows that knocking out the Exon 2 of <i>KLF7</i> facilitates the expression of gene sets associated with cancer compared with that in wild-type HeLa cells ( <i>P</i><0.05). Moreover, the administration of alpha-lipoic acid (ALA) leads to a reduction in KLF7 expression in cells and tumor tissues, a suppression of the proliferation, migration, and invasion of HeLa and SiHa cells ( <i>P</i><0.05), and an increase in the carcinogenic potential of HeLa cells ( <i>P</i><0.05), while KLF7 overexpression shows the opposite effect on the expressions of ACADL and PFKL in HeLa and SiHa cells. In conclusion, KLF7 promotes the development of cervical cancer, and ALA can downregulate KLF7 expression and play a positive role in cervical cancer treatment.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142851786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yuming Cao, Shengnan Wang, Jie Liu, Jinfeng Xu, Yan Liang, Fei Ao, Zexiao Wei, Li Wang
{"title":"CARF regulates the alternative splicing and piwi/piRNA complexes during mouse spermatogenesis through PABPC1.","authors":"Yuming Cao, Shengnan Wang, Jie Liu, Jinfeng Xu, Yan Liang, Fei Ao, Zexiao Wei, Li Wang","doi":"10.3724/abbs.2024224","DOIUrl":"https://doi.org/10.3724/abbs.2024224","url":null,"abstract":"<p><p>ADP-ribosylation factor collaborator (CARF), which is also known as CDKN2AIP, was first recognized as an ADP-ribosylation factor-interacting protein that participates in the activation of the ARF-p53-p21 (WAF1) signaling pathway under different conditions, such as oxidative and oncogenic stresses. The activation of this pathway often leads to cell growth arrest and apoptosis as well as senescence. Previous studies revealed that CARF, an RNA-binding protein, is critical for maintaining stem cell pluripotency and somatic differentiation. Nevertheless, its involvement in spermatogenesis has not been well examined. In this study, we show that male mice deficient in <i>Carf</i> expression present impaired spermatogenesis and fertility. IP-MS and RNA-seq analyses reveal that CARF/ <i>Carf</i> interacts with multiple key splicing factors, such as PABPC1, and directly targets 356 different types of mRNAs in spermatocytes. <i>Carf</i>-associated mRNAs display aberrant splicing patterns when Carf expression is deficient. In addition, our results demonstrate that PIWIL1 expression and localization are altered in the <i>Carf</i> <sup><i>-</i>/ <i>-</i></sup> mouse model through the downregulation of PABPC1, which further affects the ratio of pachytene-piRNA. Our study suggests that CARF is critical for regulating alternative splicing in mammalian spermatogenesis and determining infertility in male mice.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142852017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zi Yan, Wenhui Zhao, Naixin Zhao, Yufeng Liu, Bowen Yang, Li Wang, Jingyi Liu, Deping Wang, Jin Wang, Xiangying Jiao, Jimin Cao, Jianguo Li
{"title":"PRMT1 alleviates isoprenaline-induced myocardial hypertrophy by methylating SRSF1.","authors":"Zi Yan, Wenhui Zhao, Naixin Zhao, Yufeng Liu, Bowen Yang, Li Wang, Jingyi Liu, Deping Wang, Jin Wang, Xiangying Jiao, Jimin Cao, Jianguo Li","doi":"10.3724/abbs.2024175","DOIUrl":"https://doi.org/10.3724/abbs.2024175","url":null,"abstract":"<p><p>Myocardial hypertrophy (MH) is an important factor contributing to severe cardiovascular disease. Previous studies have demonstrated that specific deletion of the protein arginine methyltransferase 1 (PRMT1) leads to MH, but the exact mechanism remains unclear. Serine/arginine-rich splicing factor 1 (SRSF1) affects the development and progression of cardiovascular disease by selectively splicing downstream signaling proteins. The present study is designed to determine whether PRMT1 is involved in MH by regulating SRSF1 and, if so, to explore the underlying mechanisms. Adult male mice and H9C2 cardiomyocytes are treated with isoprenaline (ISO) to establish MH models. The expression levels of PRMT1 are significantly decreased in the ISO-induced MH models, and inhibiting PRMT1 worsens MH, whereas overexpression of PRMT1 ameliorates MH. SRSF1 serves as the downstream target of PRMT1, and its expression is markedly elevated in MH. Moreover, SRSF1 increases the mRNA expressions of CaMKIIδ A and CaMKIIδ B, decreases the mRNA expression of CaMKIIδ C by altering the selective splicing of CaMKIIδ, and further participates in MH. In addition, there is an interaction between PRMT1 and SRSF1, whereby PRMT1 reduces the phosphorylation level of SRSF1 via methylation, thus further altering its functional activity and eventually improving MH. Our present study demonstrates that PRMT1 relieves MH by methylating SRSF1, which is expected to provide a new theoretical basis for the pathogenic mechanism of MH and potential drug targets for reducing MH and associated cardiovascular disease.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Coupling of alternative splicing and alternative polyadenylation.","authors":"Xueying Zhang, Feiyan Liu, Yu Zhou","doi":"10.3724/abbs.2024211","DOIUrl":"https://doi.org/10.3724/abbs.2024211","url":null,"abstract":"<p><p>RNA splicing and 3'-cleavage and polyadenylation (CPA) are essential processes for the maturation of RNA. There have been extensive independent studies of these regulated processing events, including alternative splicing (AS) and alternative polyadenylation (APA). However, growing evidence suggests potential crosstalk between splicing and 3'-end processing in regulating AS or APA. Here, we first provide a brief overview of the molecular machines involved in splicing and 3'-end processing events, and then review recent studies on the functions and mechanisms of the crosstalk between the two processes. On one hand, 3'-end processing can affect splicing, as 3'-end processing factors and CPA-generated polyA tail promote the splicing of the last intron. Beyond that, 3'-end processing factors can also influence the splicing of internal and terminal exons. Those 3'-end processing factors can also interact with different RNA-binding proteins (RBPs) to exert their effects on AS. The length of 3' untranslated region (3' UTR) can affect the splicing of upstream exons. On the other hand, splicing and CPA may compete within introns in generating different products. Furthermore, splicing within the 3' UTR is a significant factor contributing to 3' UTR diversity. Splicing also influences 3'-end processing through the actions of certain splicing factors. Interestingly, some classical RBPs play dual roles in both splicing and 3'-end processing. Finally, we discuss how long-read sequencing technologies aid in understanding the coordination of AS-APA events and envision that these findings may potentially promote the development of new strategies for disease diagnosis and treatment.</p>","PeriodicalId":6978,"journal":{"name":"Acta biochimica et biophysica Sinica","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142778997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}