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Zhang J, Huang X, Zhang T, Gu C, Zuo W, Fu L, Dong Y, Liu H. Antitumorigenic potential of Lactobacillus-derived extracellular vesicles: p53 succinylation and glycolytic reprogramming in intestinal epithelial cells via SIRT5 modulation. Cell Biol Toxicol 2024; 40:66. [PMID: 39110260 PMCID: PMC11306434 DOI: 10.1007/s10565-024-09897-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Accepted: 06/21/2024] [Indexed: 08/10/2024]
Abstract
OBJECTIVE Colorectal cancer progression involves complex cellular mechanisms. This study examines the effects of Lactobacillus plantarum-derived extracellular vesicles (LEVs) on the SIRT5/p53 axis, focusing on glycolytic metabolic reprogramming and abnormal proliferation in intestinal epithelial cells. METHODS LEVs were isolated from Lactobacillus plantarum and incubated with Caco-2 cells. Differential gene expression was analyzed through RNA sequencing and compared with TCGA-COAD data. Key target genes and pathways were identified using PPI network and pathway enrichment analysis. Various assays, including RT-qPCR, EdU staining, colony formation, flow cytometry, and Western blotting, were used to assess gene expression, cell proliferation, and metabolic changes. Co-immunoprecipitation confirmed the interaction between SIRT5 and p53, and animal models were employed to validate in vivo effects. RESULTS Bioinformatics analysis indicated the SIRT5/p53 axis as a critical pathway in LEVs' modulation of colorectal cancer. LEVs were found to inhibit colorectal cancer cell proliferation and glycolytic metabolism by downregulating SIRT5, influencing p53 desuccinylation. In vivo, LEVs regulated this axis, reducing tumor formation in mice. Clinical sample analysis showed that SIRT5 and p53 succinylation levels correlated with patient prognosis. CONCLUSION Lactobacillus-derived extracellular vesicles play a pivotal role in suppressing colonic tumor formation by modulating the SIRT5/p53 axis. This results in decreased glycolytic metabolic reprogramming and reduced proliferation in intestinal epithelial cells.
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Affiliation(s)
- Jingbo Zhang
- Department of Spleen and Stomach Disease, Yubei District Hospital of Traditional Chinese Medicine, Chongqing, 401120, China
| | - Xiumei Huang
- Department of Digestion, Rongchang District People's Hospital of Chongqing, No.3, North Guangchang Road, Changyuan Street, Rongchang District, Chongqing, 402460, China
| | - Tingting Zhang
- Department of Digestion, Rongchang District People's Hospital of Chongqing, No.3, North Guangchang Road, Changyuan Street, Rongchang District, Chongqing, 402460, China
| | - Chongqi Gu
- Department of Pediatrics, Rongchang District People's Hospital, Chongqing, 402460, China
| | - Wei Zuo
- Department of Herbal Medicine, School of Traditional Chinese Medicine, Chongqing Medical University, Chongqing, 400016, China
- Department of Pharmacology, Academician Workstation, Changsha Medical University, Changsha, 410219, China
| | - Lijuan Fu
- Department of Herbal Medicine, School of Traditional Chinese Medicine, Chongqing Medical University, Chongqing, 400016, China
- Department of Pharmacology, Academician Workstation, Changsha Medical University, Changsha, 410219, China
| | - Yiping Dong
- Department of Digital Medicine, Department of Bioengineering and Imaging, Army Medical University, Chongqing, 400038, China
| | - Hao Liu
- Department of Pediatrics, Rongchang District People's Hospital, Chongqing, 402460, China.
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Huang ZM, Kang JQ, Chen PZ, Deng LF, Li JX, He YX, Liang J, Huang N, Luo TY, Lan QW, Chen HK, Guo XG. Identifying the Interaction Between Tuberculosis and SARS-CoV-2 Infections via Bioinformatics Analysis and Machine Learning. Biochem Genet 2024; 62:2606-2630. [PMID: 37991568 DOI: 10.1007/s10528-023-10563-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Accepted: 10/25/2023] [Indexed: 11/23/2023]
Abstract
The number of patients with COVID-19 caused by severe acute respiratory syndrome coronavirus 2 is still increasing. In the case of COVID-19 and tuberculosis (TB), the presence of one disease affects the infectious status of the other. Meanwhile, coinfection may result in complications that make treatment more difficult. However, the molecular mechanisms underpinning the interaction between TB and COVID-19 are unclear. Accordingly, transcriptome analysis was used to detect the shared pathways and molecular biomarkers in TB and COVID-19, allowing us to determine the complex relationship between COVID-19 and TB. Two RNA-seq datasets (GSE114192 and GSE163151) from the Gene Expression Omnibus were used to find concerted differentially expressed genes (DEGs) between TB and COVID-19 to identify the common pathogenic mechanisms. A total of 124 common DEGs were detected and used to find shared pathways and drug targets. Several enterprising bioinformatics tools were applied to perform pathway analysis, enrichment analysis and networks analysis. Protein-protein interaction analysis and machine learning was used to identify hub genes (GAS6, OAS3 and PDCD1LG2) and datasets GSE171110, GSE54992 and GSE79362 were used for verification. The mechanism of protein-drug interactions may have reference value in the treatment of coinfection of COVID-19 and TB.
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Affiliation(s)
- Ze-Min Huang
- Department of Clinical Laboratory Medicine, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China
- Department of Clinical Medicine, The Third Clinical School of Guangzhou Medical University, Guangzhou, 511436, China
| | - Jia-Qi Kang
- Department of Clinical Laboratory Medicine, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China
- Department of Clinical Medicine, The First Clinical School of Guangzhou Medical University, Guangzhou, 511436, China
| | - Pei-Zhen Chen
- Department of Clinical Laboratory Medicine, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China
- Department of Clinical Medicine, The Third Clinical School of Guangzhou Medical University, Guangzhou, 511436, China
| | - Lin-Fen Deng
- Department of Clinical Laboratory Medicine, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China
- Department of Clinical Medicine, The Third Clinical School of Guangzhou Medical University, Guangzhou, 511436, China
| | - Jia-Xin Li
- Department of Clinical Medicine, The First Clinical School of Guangzhou Medical University, Guangzhou, 511436, China
| | - Ying-Xin He
- Clinical Laboratory Medicine, Guangzhou Medical University, Guangzhou, 510006, China
| | - Jie Liang
- Department of Clinical Laboratory Medicine, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China
- Department of Clinical Medicine, The Third Clinical School of Guangzhou Medical University, Guangzhou, 511436, China
| | - Nan Huang
- Clinical Laboratory Medicine, Guangzhou Medical University, Guangzhou, 510006, China
| | - Tian-Ye Luo
- Department of Clinical Laboratory Medicine, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China
- Department of Clinical Medicine, The Third Clinical School of Guangzhou Medical University, Guangzhou, 511436, China
| | - Qi-Wen Lan
- Department of Clinical Medicine, The Second Clinical School of Guangzhou Medical University, Guangzhou, 511436, China
| | - Hao-Kai Chen
- Department of Clinical Laboratory Medicine, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China
- Department of Clinical Medicine, The Third Clinical School of Guangzhou Medical University, Guangzhou, 511436, China
| | - Xu-Guang Guo
- Department of Clinical Laboratory Medicine, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China.
- Department of Clinical Laboratory Medicine, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China.
- Guangzhou Key Laboratory for Clinical Rapid Diagnosis and Early Warning of Infectious Diseases, King Med School of Laboratory Medicine, Guangzhou Medical University, Guangzhou, 510000, China.
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Liao B, Wang J, Yuan Y, Luo H, Ouyang X. Biological roles of SLC16A1-AS1 lncRNA and its clinical impacts in tumors. Cancer Cell Int 2024; 24:122. [PMID: 38555465 PMCID: PMC10981830 DOI: 10.1186/s12935-024-03285-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2023] [Accepted: 02/27/2024] [Indexed: 04/02/2024] Open
Abstract
Recent studies have increasingly highlighted the aberrant expression of SLC16A1-AS1 in a variety of tumor types, where it functions as either an oncogene or a tumor suppressor in the pathogenesis of different cancers. The expression levels of SLC16A1-AS1 have been found to significantly correlate with clinical features and the prognosis of cancer patients. Furthermore, SLC16A1-AS1 modulates a range of cellular functions, including proliferation, migration, and invasion, through its interactions with diverse molecules and signaling pathways. This review examines the latest evidence regarding the role of SLC16A1-AS1 in the progression of various tumors and explores its potential clinical applications as a novel prognostic and diagnostic biomarker. Our comprehensive review aims to deepen the understanding of SLC16A1-AS1's multifaceted role in oncology, underscoring its potential as a significant biomarker and therapeutic target.
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Affiliation(s)
- Bing Liao
- Department of Otorhinolaryngology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330008, Jiangxi, China
| | - Jialing Wang
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330008, Jiangxi, China
| | - Yalin Yuan
- Second School of Clinical Medicine, Jiangxi Medical College, Nanchang University, Nanchang, 330008, Jiangxi, China
| | - Hongliang Luo
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330008, Jiangxi, China
| | - Xi Ouyang
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330008, Jiangxi, China.
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Tao ZG, Yuan YX, Wang GW. Long non-coding RNA CDKN2B-AS1 promotes hepatocellular carcinoma progression via E2F transcription factor 1/G protein subunit alpha Z axis. World J Gastrointest Oncol 2023; 15:1974-1987. [DOI: 10.4251/wjgo.v15.i11.1974] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Revised: 09/12/2023] [Accepted: 10/11/2023] [Indexed: 11/15/2023] Open
Abstract
BACKGROUND A series of long non-coding RNAs (lncRNAs) have been reported to play a crucial role in cancer biology. Some previous studies report that lncRNA CDKN2B-AS1 is involved in some human malignancies. However, its role in hepatocellular carcinoma (HCC) has not been fully deciphered.
AIM To decipher the role of CDKN2B-AS1 in the progression of HCC.
METHODS CDKN2B-AS1 expression in HCC was detected by quantitative real-time polymerase chain reaction. The malignant phenotypes of Li-7 and SNU-182 cells were detected by the CCK-8 method, EdU method, and flow cytometry, respectively. RNA immunoprecipitation was executed to confirm the interaction between CDKN2B-AS1 and E2F transcription factor 1 (E2F1). Luciferase reporter assay and chromatin immunoprecipitation were performed to verify the binding of E2F1 to the promoter of G protein subunit alpha Z (GNAZ). E2F1 and GNAZ were detected by western blot in HCC cells.
RESULTS In HCC tissues, CDKN2B-AS1 was upregulated. Depletion of CDKN2B-AS1 inhibited the proliferation of HCC cells, and the depletion of CDKN2B-AS1 also induced cell cycle arrest and apoptosis. CDKN2B-AS1 could interact with E2F1. Depletion of CDKN2B-AS1 inhibited the binding of E2F1 to the GNAZ promoter region. Overexpression of E2F1 reversed the biological effects of depletion of CDKN2B-AS1 on the malignant behaviors of HCC cells.
CONCLUSION CDKN2B-AS1 recruits E2F1 to facilitate GNAZ transcription to promote HCC progression.
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Affiliation(s)
- Zhi-Gang Tao
- Department of Radiology, Hangzhou Cancer Hospital, Hangzhou 310000, Zhejiang Province, China
| | - Yu-Xiao Yuan
- Department of Radiology, Hangzhou Xixi Hospital, Hangzhou 310012, Zhejiang Province, China
| | - Guo-Wei Wang
- Department of Radiology, Hangzhou Xixi Hospital, Hangzhou 310012, Zhejiang Province, China
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Fan T, Chen X, Yang F, Li Y, Gao Q, Li S, Chen X, Chen X. A network pharmacology and bioinformatics exploration of the possible molecular mechanisms of Fuzheng Xiaoliu Granule for the treatment of hepatocellular carcinoma. J Clin Transl Res 2023; 9:182-194. [PMID: 37275579 PMCID: PMC10238106] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Revised: 01/22/2023] [Accepted: 04/10/2023] [Indexed: 06/07/2023] Open
Abstract
Background and Aim Hepatocellular carcinoma (HCC) is one of the ten most common malignant tumors in the world, and it is a major problem in the world. Traditional Chinese medicine (TCM) has many advantages in the prevention and treatment of HCC, but its complicated mechanism of action is difficult to clarify, which limits its research and development. The continuous development of bioinformation technology provides new methods and opportunities for the research of TCM. This study used modern network pharmacology and bioinformatic methods to explore the possible molecular mechanism of the Chinese herbal compound Fuzheng Xiaoliu Granule (FZXLG) to treat HCC, to provide a theoretical basis for their clinical application and basic research, to promote the modernization of TCM, and to promote its worldwide application. Methods The active ingredients of FZXLG were collected and screened through TCMSP, BATMAN-TCM, and other databases. The targets of FZXLG were predicted by PubChem and SwissTargetPrediction; HCC disease-related targets were obtained by GeneCards, OMIM, and other disease databases, and the potential gene targets of FZXLG for HCC treatment were screened. The "Prescription-TCMs-Ingredients-Targets" network of FZXLG for the treatment of HCC was constructed, along with the screening of core effective components. The differentially expressed genes (DEGs) of HCC tumor and non-tumor adjacent tissues combined with clinical data in the TCGA database were analyzed to obtain the prognostic genes of HCC. Then, FZXLG genes affecting HCC prognosis were screened and further screening the core target genes. The correlation between core gene expression with prognosis, immune cell infiltration, and immunohistochemical changes in HCC patients was studied. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and Gene Ontology enrichment analysis of the FZXLG genes affecting HCC prognosis were performed using DAVID database. AutoDockTools software was then used for molecular docking verification. Results The ten core effective ingredients of FZXLG for HCC treatment included multiple flavonoids ingredients such as quercetin, luteolin, and formononetin. 11 core targets of FZXLG affecting the prognosis of HCC were screened, among which estrogen receptor 1 (ESR1) and catalase (CAT) were favorable prognostic factors, while EGF, MMP9, CCNA2, CCNB1, CDK1, CHEK1, and E2F1 were adverse prognostic factors. MMP9 and EGF were positively correlated with six TIIC subsets. The different expression levels of CAT, PLG, AR, MMP9, CCNA2, CCNB1, CDK1, and E2F1 were correlated with the immunohistochemical staining changes in normal liver and liver cancer. KEGG pathway enrichment analysis yielded 33 pathways including cell cycle, p53, hepatitis B, and other signaling pathways. Molecular docking verified that the main core components had good binding to the protective prognostic core targets ESR1 and CAT. Conclusions FZXLG may treat HCC through multiple ingredients, multiple targets, and multiple pathways, affecting the prognosis, immune microenvironment, and immunohistochemical changes of HCC. Relevance for Patients FZXLG is a Chinese herbal compound for the treatment of HCC, with significant clinical efficacy. However, the mechanism of action is unclear and lacks theoretical support, which limits its popularization application. This study preliminarily revealed its molecular mechanism, providing a theoretical basis for its clinical application, which can better guide its clinical popularization application, and also provide a new strategy for the treatment of HCC.
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Affiliation(s)
- Tianyu Fan
- Department of Gastroenterology, Henan University of Chinese Medicine, Zhengzhou City 450000, Henan Province, China
| | - Xi Chen
- Department of Gastroenterology, Henan University of Chinese Medicine, Zhengzhou City 450000, Henan Province, China
| | - Fangming Yang
- Department of Gastroenterology, The First Affiliated Hospital of Henan University of CM, Zhengzhou City 450000, Henan Province, China
| | - Yanjie Li
- Department of Gastroenterology, Henan University of Chinese Medicine, Zhengzhou City 450000, Henan Province, China
| | - Qi Gao
- Department of Gastroenterology, Henan University of Chinese Medicine, Zhengzhou City 450000, Henan Province, China
| | - Shanyi Li
- Department of Gastroenterology, Henan University of Chinese Medicine, Zhengzhou City 450000, Henan Province, China
| | - Xinju Chen
- Department of Gastroenterology, The First Affiliated Hospital of Henan University of CM, Zhengzhou City 450000, Henan Province, China
| | - Xiaoqi Chen
- Department of Gastroenterology, The First Affiliated Hospital of Henan University of CM, Zhengzhou City 450000, Henan Province, China
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