Juan An, Lang Yang, Yuanming Pan, Yuqi He, Hui Xie, Yurong Tao, Wei Li, Yupeng Yan, Siai Chen, Ya Liu, Xiaoming Ma, Ling An, Dongde Ji, Zhanhai Su, Jianqiu Sheng
{"title":"SPAG5激活PI3K/AKT通路,促进癌症的肿瘤进展和化疗耐药性。","authors":"Juan An, Lang Yang, Yuanming Pan, Yuqi He, Hui Xie, Yurong Tao, Wei Li, Yupeng Yan, Siai Chen, Ya Liu, Xiaoming Ma, Ling An, Dongde Ji, Zhanhai Su, Jianqiu Sheng","doi":"10.1089/dna.2021.0531","DOIUrl":null,"url":null,"abstract":"<p><p>The sperm-associated antigen 5 (SPAG5) is an important protein in mitosis and cell cycle checkpoint regulation, with more attention as a novel oncogene in various cancers. High level of SPAG5 expression has been detected in our clinical gastric cancer (GC) samples and The Cancer Genome Atlas GC data. However, the bio-function and potential mechanism of SPAG5 in GC remain unclear. In this study, we investigated the role of SPAG5 in GC development and the correlation between SPAG5 and 5-fluorouracil (5-FU) treatment. SPAG5 expression was increased in GC samples compared with that in normal tissues (80.8% vs. 22.0%), which was apparently associated with a worse outcome. Biological experiments showed that knockdown of SPAG5 induced apoptosis and suppressed proliferation in cells and animal models. Downregulation of SPAG5 enhanced the sensitivity of 5-FU in GC cells. Gene microarray chip identified 856 upregulated and 787 downregulated genes in SPAG5 silencing cells. Furthermore, 12 significant genes, including CDKN1A, CDKN1B, EIF4E, MAPK1, and HSP90B1, belonged to the PI3K/AKT signaling pathway using ingenuity pathway analysis. Meanwhile, real-time PCR and Western blotting results showed that knockdown of SPAG5 inhibited PI3K/AKT signaling pathway. Collectively, SPAG5 promotes the growth of GC cells by regulating PI3K/AKT signaling pathway, which could be the promising target gene in GC therapy.</p>","PeriodicalId":11248,"journal":{"name":"DNA and cell biology","volume":null,"pages":null},"PeriodicalIF":2.6000,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":"{\"title\":\"SPAG5 Activates PI3K/AKT Pathway and Promotes the Tumor Progression and Chemo-Resistance in Gastric Cancer.\",\"authors\":\"Juan An, Lang Yang, Yuanming Pan, Yuqi He, Hui Xie, Yurong Tao, Wei Li, Yupeng Yan, Siai Chen, Ya Liu, Xiaoming Ma, Ling An, Dongde Ji, Zhanhai Su, Jianqiu Sheng\",\"doi\":\"10.1089/dna.2021.0531\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>The sperm-associated antigen 5 (SPAG5) is an important protein in mitosis and cell cycle checkpoint regulation, with more attention as a novel oncogene in various cancers. High level of SPAG5 expression has been detected in our clinical gastric cancer (GC) samples and The Cancer Genome Atlas GC data. However, the bio-function and potential mechanism of SPAG5 in GC remain unclear. In this study, we investigated the role of SPAG5 in GC development and the correlation between SPAG5 and 5-fluorouracil (5-FU) treatment. SPAG5 expression was increased in GC samples compared with that in normal tissues (80.8% vs. 22.0%), which was apparently associated with a worse outcome. Biological experiments showed that knockdown of SPAG5 induced apoptosis and suppressed proliferation in cells and animal models. Downregulation of SPAG5 enhanced the sensitivity of 5-FU in GC cells. Gene microarray chip identified 856 upregulated and 787 downregulated genes in SPAG5 silencing cells. Furthermore, 12 significant genes, including CDKN1A, CDKN1B, EIF4E, MAPK1, and HSP90B1, belonged to the PI3K/AKT signaling pathway using ingenuity pathway analysis. Meanwhile, real-time PCR and Western blotting results showed that knockdown of SPAG5 inhibited PI3K/AKT signaling pathway. Collectively, SPAG5 promotes the growth of GC cells by regulating PI3K/AKT signaling pathway, which could be the promising target gene in GC therapy.</p>\",\"PeriodicalId\":11248,\"journal\":{\"name\":\"DNA and cell biology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.6000,\"publicationDate\":\"2022-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"DNA and cell biology\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1089/dna.2021.0531\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"DNA and cell biology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1089/dna.2021.0531","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
SPAG5 Activates PI3K/AKT Pathway and Promotes the Tumor Progression and Chemo-Resistance in Gastric Cancer.
The sperm-associated antigen 5 (SPAG5) is an important protein in mitosis and cell cycle checkpoint regulation, with more attention as a novel oncogene in various cancers. High level of SPAG5 expression has been detected in our clinical gastric cancer (GC) samples and The Cancer Genome Atlas GC data. However, the bio-function and potential mechanism of SPAG5 in GC remain unclear. In this study, we investigated the role of SPAG5 in GC development and the correlation between SPAG5 and 5-fluorouracil (5-FU) treatment. SPAG5 expression was increased in GC samples compared with that in normal tissues (80.8% vs. 22.0%), which was apparently associated with a worse outcome. Biological experiments showed that knockdown of SPAG5 induced apoptosis and suppressed proliferation in cells and animal models. Downregulation of SPAG5 enhanced the sensitivity of 5-FU in GC cells. Gene microarray chip identified 856 upregulated and 787 downregulated genes in SPAG5 silencing cells. Furthermore, 12 significant genes, including CDKN1A, CDKN1B, EIF4E, MAPK1, and HSP90B1, belonged to the PI3K/AKT signaling pathway using ingenuity pathway analysis. Meanwhile, real-time PCR and Western blotting results showed that knockdown of SPAG5 inhibited PI3K/AKT signaling pathway. Collectively, SPAG5 promotes the growth of GC cells by regulating PI3K/AKT signaling pathway, which could be the promising target gene in GC therapy.
期刊介绍:
DNA and Cell Biology delivers authoritative, peer-reviewed research on all aspects of molecular and cellular biology, with a unique focus on combining mechanistic and clinical studies to drive the field forward.
DNA and Cell Biology coverage includes:
Gene Structure, Function, and Regulation
Gene regulation
Molecular mechanisms of cell activation
Mechanisms of transcriptional, translational, or epigenetic control of gene expression
Molecular Medicine
Molecular pathogenesis
Genetic approaches to cancer and autoimmune diseases
Translational studies in cell and molecular biology
Cellular Organelles
Autophagy
Apoptosis
P bodies
Peroxisosomes
Protein Biosynthesis and Degradation
Regulation of protein synthesis
Post-translational modifications
Control of degradation
Cell-Autonomous Inflammation and Host Cell Response to Infection
Responses to cytokines and other physiological mediators
Evasive pathways of pathogens.