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}
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}
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}
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":"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, and the high level of <i>KLF7</i> transcripts in cervical cancer tissues is negatively correlated with patients' overall and disease-free survival. 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>. 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, 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. 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, and an increase in the carcinogenic potential of HeLa cells, 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":"237-249"},"PeriodicalIF":3.3,"publicationDate":"2024-12-17","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}
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}
Meng Zhang, Jiafeng Sha, Na Li, Jingjing Feng, Tianyun Shi, Yunxia Yu, Xiaoting Ren, Zhoufang Mei, Zhijun Jie
{"title":"Early RSV infection aggravates asthma-related Th2 responses by increasing the number of CD4 <sup>+</sup> TRM cells through upregulation of PLZF.","authors":"Meng Zhang, Jiafeng Sha, Na Li, Jingjing Feng, Tianyun Shi, Yunxia Yu, Xiaoting Ren, Zhoufang Mei, Zhijun Jie","doi":"10.3724/abbs.2024220","DOIUrl":"https://doi.org/10.3724/abbs.2024220","url":null,"abstract":"<p><p>Respiratory syncytial virus (RSV) infection is correlated with the chronic pathogenesis and exacerbation of asthma. However, the mechanism remains unclear. In this study, acute and memory (Mem) asthma models with early RSV infection are established to explore the persistence of the effects of RSV infection on asthma. Intravascular injection of an anti-CD45 antibody is performed to define CD4 <sup>+</sup> TRM cells accurately. RSV infection has a sustained impact on asthma exacerbation for at least six weeks, with high Th2 cytokine secretion in lung tissue instead of IgE response-related B cells. CD45 <sup>-</sup>CD4 <sup>+</sup> TRM cells are positively correlated with RSV-related asthma exacerbation and severe airway inflammation. Mechanistically, overexpression of the transcription factor PLZF <i>in vitro</i> increases the number of CD4 <sup>+</sup> TRM cells, and conditional knockout of <i>Zbtb16</i> (encoding PLZF) can decrease the number of CD4 <sup>+</sup> TRM cells to aggravate allergic inflammation and reduce Th2 responses. This study provides evidence for potential combined strategies that might benefit asthma patients.</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":"142779002","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}
Xiongshan Sun, Jia Wang, Yi Xiao, De Li, Qiang Wang, Wei Guo, Yongjian Yang
{"title":"Skeletal muscle-derived musclin attenuates glycolysis, oxidative stress, and pulmonary hypertension through the NPR3/AKT/mTORC1 pathway.","authors":"Xiongshan Sun, Jia Wang, Yi Xiao, De Li, Qiang Wang, Wei Guo, Yongjian Yang","doi":"10.3724/abbs.2024214","DOIUrl":"https://doi.org/10.3724/abbs.2024214","url":null,"abstract":"<p><p>Exercise ameliorates pulmonary hypertension (PH) progression. However, the underlying mechanisms are largely unclear. Musclin is an exercise-responsive myokine that exerts protective effects on cardiovascular diseases. The current study aims to explore the role of musclin in the development of PH. A monocrotaline (MCT)-induced mouse PH model is established. Adeno-associated virus serotype 6 (AAV6)-mediated gene transfer is used to induce musclin overexpression in skeletal muscle. Ultrasound and morphological analyses are utilized to assess the severity of PH. Cell viability assay, Ki-67 immunofluorescence staining, wound healing assay, and transwell assay are used to evaluate the proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs). We find that the musclin levels in both plasma and skeletal muscle are decreased in MCT-treated mice. The external expression of musclin in skeletal muscle ameliorates pulmonary arterial remodeling and right ventricular dysfunction. <i>In vitro</i>, musclin treatment suppresses hypoxia-induced glycolysis, oxidative stress, proliferation, and migration. Further experiments reveal that musclin inhibits mechanistic target of rapamycin complex 1 (mTORC1) activity in hypoxia-stimulated PASMCs and pulmonary arteries of MCT-treated mice. Reactivating mTORC1 abolishes the protective role of musclin against PH. Additionally, musclin enhances its interaction with natriuretic peptide receptor 3 (NPR3) in PASMCs. Silencing of <i>NPR3</i> reverses the inhibitory effects of musclin on AKT phosphorylation, mTORC1 activity, glycolysis, oxidative stress, proliferation, and migration in hypoxia-challenged PASMCs. In conclusion, our study highlights the inhibitory role of musclin in the proliferation and migration of PASMCs and PH progression, thereby providing a novel potent therapeutic strategy for treating PH and partly clarifying the mechanism of exercise-mediated protection against PH.</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":"142779019","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":"Cardioprotective effect of <i>Saussurea involucrata</i> injection against Doxorubicin-induced cardiotoxicity by network pharmacology analysis and experimental verification.","authors":"Ding Wang, Yu Jin, Mengyu Yang, Yajing Xue, Xiaotong Zhang, Yanli Guo, Xinzhi Li, Ketao Ma","doi":"10.3724/abbs.2024170","DOIUrl":"https://doi.org/10.3724/abbs.2024170","url":null,"abstract":"<p><p>Doxorubicin (Dox) is widely utilized in the clinical treatment of various cancers. Despite its efficacy, Dox induces numerous adverse effects in humans with significant cardiotoxicity, posing a major limitation to its use. <i>Saussurea involucrata</i> injection (SII), derived from <i>Saussurea involucrata</i>, exhibits notable anti-inflammatory and anti-oxidative stress properties. However, its potential protective effects against Dox-induced cardiotoxicity (DIC) remain unexplored. In this study, we investigate the ability of SII to mitigate DIC and elucidate the underlying mechanisms through experimental research and network pharmacology analysis. Results from both <i>in vitro</i> and <i>in vivo</i> experiments reveal that SII treatment significantly improves Dox-induced cardiac dysfunction, reducing pathological alterations and fibrosis in cardiomyocytes. Moreover, SII has cardioprotective effects by diminishing the inflammation, oxidative stress, and apoptosis triggered by Dox. Network pharmacological analysis further shows that SII downregulates P53 protein expression by activating the AKT/MDM2 signaling pathway, thus attenuating DIC. In conclusion, this study confirms that SII mitigates DIC through downregulation of the AKT/MDM2/P53 signaling pathway, suggesting a promising therapeutic strategy for alleviating DIC.</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":"142778941","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}