|
1
|
Wang Z, Shi D, Li X, Wang X, Bai J. KIF20A promotes triple-negative breast cancer progression via activation of the IL-17 signaling pathway. Biochem Biophys Res Commun 2025; 770:152031. [PMID: 40393105 DOI: 10.1016/j.bbrc.2025.152031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2025] [Revised: 05/07/2025] [Accepted: 05/14/2025] [Indexed: 05/22/2025]
Abstract
BACKGROUND Triple-negative breast cancer (TNBC), the only breast cancer subtype lacking effective targeted therapies, is associated with a poor prognosis. Emerging evidence highlights the oncogenic role of kinesin family member 20A (KIF20A) in human malignancies, though its mechanistic contributions to TNBC progression remain poorly understood. METHODS Candidate target genes were screened via bioinformatic analysis. Following KIF20A knockdown, we utilized cell counting kit-8, 5-Ethynyl-2'-deoxyuridine staining, transwell, and wound healing assays to assess TNBC cell viability, proliferative capacity, migratory ability, and invasive potential of TNBC cells. In vivo, we measured the volume, weight, and proliferation of solid tumors. Moreover, the downstream pathway of KIF20A was screened by bioinformatic analysis and validated by an agonist and an inhibitor for the interleukin 17 (IL-17) pathway. The expression levels of proteins associated with the IL-17 pathway were assessed via Western blot. RESULTS KIF20A, highly overexpressed in TNBC, was screened out as a promising target gene. In vitro, KIF20A knockdown significantly impaired TNBC cell viability, proliferation, migration, and invasion. In vivo, KIF20A knockdown suppressed the growth and proliferation of solid tumors in nude mice xenograft models. Mechanistically, the IL-17 signaling pathway was screened out and the expression of proteins in this pathway was suppressed by KIF20A knockdown. The agonist for the IL-17 signaling countered the impact of KIF20A knockdown on TNBC progression. Direct inhibition of IL-17 showed a similar effect as KIF20A silencing on TNBC cells. CONCLUSION KIF20A downregulation suppresses TNBC progression via the inactivation of the IL-17 signaling pathway, suggesting KIF20A as a potential therapeutic target for TNBC.
Collapse
Affiliation(s)
- Zhiyong Wang
- Department of Thyroid and Breast Surgery, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China
| | - Dongning Shi
- Department of Thyroid and Breast Surgery, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China
| | - Xin Li
- Department of Thyroid and Breast Surgery, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China
| | - Xia Wang
- Department of Thyroid and Breast Surgery, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China
| | - Junwen Bai
- Department of Thyroid and Breast Surgery, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China.
| |
Collapse
|
|
2
|
Sanghvi G, R R, Kashyap A, Sabarivani A, Ray S, Bhakuni PN. Identifying the function of kinesin superfamily proteins in gastric cancer: Implications for signal transduction, clinical significance, and potential therapeutic approaches. Clin Res Hepatol Gastroenterol 2025; 49:102571. [PMID: 40064398 DOI: 10.1016/j.clinre.2025.102571] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2025] [Revised: 03/06/2025] [Accepted: 03/08/2025] [Indexed: 03/16/2025]
Abstract
Gastric cancer (GC), a leading cause of cancer-related mortality, poses a significant global health challenge. Given its complex etiology, understanding the molecular pathways driving GC progression is crucial for developing innovative therapeutic strategies. Among the diverse proteins involved in cellular transport and mitotic regulation, kinesin superfamily proteins (KIFs) have emerged as key players in tumor biology. These motor proteins mediate intracellular transport along microtubules and are essential for processes such as cell division, signaling, and organelle distribution. Evidence indicates that specific KIFs are dysregulated in GC, potentially driving cancer cell proliferation, metastasis, and chemoresistance. Moreover, aberrant KIF expression has been associated with poorer prognoses, highlighting their potential as biomarkers for early diagnosis and therapeutic intervention. This review explores the roles of KIFs in GC and assesses their implications for research and clinical applications. By elucidating the significance of KIFs in GC, this discussion aims to inspire novel insights in cancer biology and advance targeted therapeutic strategies.
Collapse
Affiliation(s)
- Gaurav Sanghvi
- Marwadi University Research Center, Department of Microbiology, Faculty of Science, Marwadi University, Rajkot, Gujarat 360003, India
| | - Roopashree R
- Department of Chemistry and Biochemistry, School of Sciences, JAIN (Deemed to be University), Bangalore, Karnataka, India
| | - Aditya Kashyap
- Centre for Research Impact & Outcome, Chitkara University Institute of Engineering and Technology, Chitkara University, Rajpura, Punjab 140401, India
| | - A Sabarivani
- Department of Biomedical, Sathyabama Institute of Science and Technology, Chennai, Tamil Nadu, India
| | - Subhashree Ray
- Department of Biochemistry, IMS and SUM Hospital, Siksha 'O' Anusandhan (Deemed to be University), Bhubaneswar, Odisha 751003, India
| | - Pushpa Negi Bhakuni
- Department of Allied Science, Graphic Era Hill University, Bhimtal, Uttarakhand 248002, India; Graphic Era Deemed to be University, Dehradun, Uttarakhand, India.
| |
Collapse
|
|
3
|
Yang M, Huang H, Zhang Y, Wang Y, Zhao J, Lee P, Ma Y, Qu S. Identification and validation of KIF20A for predicting prognosis and treatment outcomes in patients with breast cancer. Sci Rep 2024; 14:31543. [PMID: 39733078 PMCID: PMC11682246 DOI: 10.1038/s41598-024-83362-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: 10/07/2024] [Accepted: 12/13/2024] [Indexed: 12/30/2024] Open
Abstract
Breast cancer is a leading cause of cancer-related deaths among women globally. It is imperative to explore novel biomarkers to predict breast cancer treatment response as well as progression. Here, we collected six breast cancer samples and paired normal tissues for high-throughput sequencing. By differential expression analysis, we found 1687 DEGs and identified the top 10 hub genes, including TOP2A, CDK1, BUB1B, KIF11, CCNA2, BUB1, CCNB1, KIF20A, DLGAP5 and CDC20. Univariate and multivariate Cox analyses on the METABRIC database and GSE96058 dataset demonstrated that KIF20A was an independent prognostic predictor for overall survival. KIF20A was positively correlated with cell cycle phases, including the cell cycle process, cycle G2 M phase transition and cell cycle DNA replication initiation. Single-cell analyses revealed that KIF20A was enriched in fibroblasts and endothelial within breast cancer stroma. Meanwhile, multidrug resistance (MDR) genes ABCB1, ABCC1 and ABCG2 were co-expressed with KIF20A in fibroblasts and endothelial cells within the stroma. MTABRIC database confirmed that high expression of KIF20A was positively correlated with treatment efficacy in patients with breast cancer. In conclusion, KIF20A could be served as a predictive biomarker for breast cancer prognosis and treatment outcomes. KIF20A may play a significant role by regulating cell cycle progression and modulating stromal progression in breast cancer. Our findings provided novel molecular insights that can guide personalized treatment strategies in breast cancer.
Collapse
Affiliation(s)
- Mei Yang
- Department of Breast Surgery, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China
- Department of Breast Surgery, JiangMen Maternity and Child Health Care Hospital, Jiangmen, China
| | - Hui Huang
- Department of Breast Surgery, JiangMen Maternity and Child Health Care Hospital, Jiangmen, China
| | - Yan Zhang
- Department of Breast Surgery, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China
| | - Yiping Wang
- Department of Breast Surgery, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China
| | - Junhao Zhao
- Department of Breast Surgery, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China
| | - Peiyao Lee
- Department of Breast Surgery, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China
| | - Yuhua Ma
- Department of Breast Surgery, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China.
| | - Shaohua Qu
- Department of Breast Surgery, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China.
| |
Collapse
|
|
4
|
Ma X, Huang T, Li X, Zhou X, Pan H, Du A, Zeng Y, Yuan K, Wang Z. Exploration of the link between COVID-19 and gastric cancer from the perspective of bioinformatics and systems biology. Front Med (Lausanne) 2024; 11:1428973. [PMID: 39371335 PMCID: PMC11449776 DOI: 10.3389/fmed.2024.1428973] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2024] [Accepted: 09/04/2024] [Indexed: 10/08/2024] Open
Abstract
Background Coronavirus disease 2019 (COVID-19), an infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has caused a global pandemic. Gastric cancer (GC) poses a great threat to people's health, which is a high-risk factor for COVID-19. Previous studies have found some associations between GC and COVID-19, whereas the underlying molecular mechanisms are not well understood. Methods We employed bioinformatics and systems biology to explore these links between GC and COVID-19. Gene expression profiles of COVID-19 (GSE196822) and GC (GSE179252) were obtained from the Gene Expression Omnibus (GEO) database. After identifying the shared differentially expressed genes (DEGs) for GC and COVID-19, functional annotation, protein-protein interaction (PPI) network, hub genes, transcriptional regulatory networks and candidate drugs were analyzed. Results We identified 209 shared DEGs between COVID-19 and GC. Functional analyses highlighted immune-related pathways as key players in both diseases. Ten hub genes (CDK1, KIF20A, TPX2, UBE2C, HJURP, CENPA, PLK1, MKI67, IFI6, IFIT2) were identified. The transcription factor/gene and miRNA/gene interaction networks identified 38 transcription factors (TFs) and 234 miRNAs. More importantly, we identified ten potential therapeutic agents, including ciclopirox, resveratrol, etoposide, methotrexate, trifluridine, enterolactone, troglitazone, calcitriol, dasatinib and deferoxamine, some of which have been reported to improve and treat GC and COVID-19. Conclusion This research offer valuable insights into the molecular interplay between COVID-19 and GC, potentially guiding future therapeutic strategies.
Collapse
Affiliation(s)
| | | | | | | | | | | | | | - Kefei Yuan
- Division of Liver Surgery, Department of General Surgery and Laboratory of Liver Surgery, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Zhen Wang
- Division of Liver Surgery, Department of General Surgery and Laboratory of Liver Surgery, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| |
Collapse
|
|
5
|
Moon DO. Advancing Cancer Therapy: The Role of KIF20A as a Target for Inhibitor Development and Immunotherapy. Cancers (Basel) 2024; 16:2958. [PMID: 39272816 PMCID: PMC11393963 DOI: 10.3390/cancers16172958] [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: 07/06/2024] [Revised: 08/18/2024] [Accepted: 08/22/2024] [Indexed: 09/15/2024] Open
Abstract
The analysis begins with a detailed examination of the gene expression and protein structure of KIF20A, highlighting its interaction with critical cellular components that influence key processes such as Golgi membrane transport and mitotic spindle assembly. The primary focus is on the development of specific KIF20A inhibitors, detailing their roles and the challenges encountered in enhancing their efficacy, such as achieving specificity, overcoming tumor resistance, and optimizing delivery systems. Additionally, it delves into the prognostic value of KIF20A across multiple cancer types, emphasizing its role as a novel tumor-associated antigen, which lays the groundwork for the development of targeted peptide vaccines. The therapeutic efficacy of these vaccines as demonstrated in recent clinical trials is discussed. Future directions are proposed, including the integration of precision medicine strategies to personalize treatments and the use of combination therapies to improve outcomes. By concentrating on the significant potential of KIF20A as both a direct target for inhibitors and an antigen in cancer vaccines, this review sets a foundation for future research aimed at harnessing KIF20A for effective cancer treatment.
Collapse
Affiliation(s)
- Dong Oh Moon
- Department of Biology Education, Daegu University, 201, Daegudae-ro, Gyeongsan-si 38453, Gyeongsangbuk-do, Republic of Korea
| |
Collapse
|
|
6
|
Pfisterer M, Robert R, Saul VV, Pritz A, Seibert M, Feederle R, Schmitz ML. The Aurora B-controlled PP1/RepoMan complex determines the spatial and temporal distribution of mitotic H2B S6 phosphorylation. Open Biol 2024; 14:230460. [PMID: 38806145 PMCID: PMC11293436 DOI: 10.1098/rsob.230460] [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: 12/21/2023] [Revised: 02/02/2024] [Accepted: 03/19/2024] [Indexed: 05/30/2024] Open
Abstract
The precise spatial and temporal control of histone phosphorylations is important for the ordered progression through the different phases of mitosis. The phosphorylation of H2B at S6 (H2B S6ph), which is crucial for chromosome segregation, reaches its maximum level during metaphase and is limited to the inner centromere. We discovered that the temporal and spatial regulation of this modification, as well as its intensity, are governed by the scaffold protein RepoMan and its associated catalytically active phosphatases, PP1α and PP1γ. Phosphatase activity is inhibited at the area of maximal H2B S6 phosphorylation at the inner centromere by site-specific Aurora B-mediated inactivation of the PP1/RepoMan complex. The motor protein Mklp2 contributes to the relocalization of Aurora B from chromatin to the mitotic spindle during anaphase, thus alleviating Aurora B-dependent repression of the PP1/RepoMan complex and enabling dephosphorylation of H2B S6. Accordingly, dysregulation of Mklp2 levels, as commonly observed in tumour cells, leads to the lack of H2B S6 dephosphorylation during early anaphase, which might contribute to chromosomal instability.
Collapse
Affiliation(s)
| | - Roman Robert
- Institute of Biochemistry, Justus-Liebig-University Giessen, Giessen, Germany
| | - Vera V. Saul
- Institute of Biochemistry, Justus-Liebig-University Giessen, Giessen, Germany
| | - Amelie Pritz
- Institute of Biochemistry, Justus-Liebig-University Giessen, Giessen, Germany
| | - Markus Seibert
- Institute of Biochemistry, Justus-Liebig-University Giessen, Giessen, Germany
| | - Regina Feederle
- Monoclonal Antibody Core Facility, Helmholtz Center Munich, German Research Center for Environmental Health, Neuherberg, Germany
| | - M. Lienhard Schmitz
- Institute of Biochemistry, Justus-Liebig-University Giessen, Giessen, Germany
| |
Collapse
|
|
7
|
Zhong Q, Hong W, Xiong L. KIF3C: an emerging biomarker with prognostic and immune implications across pan-cancer types and its experiment validation in gastric cancer. Aging (Albany NY) 2024; 16:6163-6187. [PMID: 38552217 PMCID: PMC11042961 DOI: 10.18632/aging.205694] [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: 11/16/2023] [Accepted: 02/08/2024] [Indexed: 04/23/2024]
Abstract
Kinesin Family Member 3C (KIF3C) assumes a crucial role in various biological processes of specific human cancers. Nevertheless, there exists a paucity of systematic assessments pertaining to the contribution of KIF3C in human malignancies. We conducted an extensive analysis of KIF3C, covering its expression profile, prognostic relevance, molecular function, tumor immunity, and drug sensitivity. Functional enrichment analysis was also carried out. In addition, we conducted in vitro experiments to substantiate the role of KIF3C in gastric cancer (GC). KIF3C expression demonstrated consistent elevation in various tumors compared to their corresponding normal tissues. We further unveiled that heightened KIF3C expression served as a prognostic indicator, and its elevated levels correlated with unfavorable clinical outcomes, encompassing reduced OS, DSS, and PFS in several cancer types. Notably, KIF3C expression exhibited positive associations with the pathological stages of several cancers. Moreover, KIF3C demonstrated varying relationships with the infiltration of various distinct immune cell types in gastric cancer. Functional analysis outcomes indicated that KIF3C played a role in the PI3K-AKT signaling pathway. Drug sensitivity unveiled a positive relationship between KIF3C in gastric cancer and the IC50 values of the majority of identified anti-cancer drugs. Additionally, KIF3C knockdown reduced the proliferation, migration, and invasion capabilities, increased apoptosis, and led to alterations in the cell cycle of gastric cancer cells. Our research has revealed the significant and functional role of KIF3C as a tumorigenic gene in diverse cancer types. These findings indicate that KIF3C may serve as a promising target for the treatment of gastric cancer.
Collapse
Affiliation(s)
- Qiangqiang Zhong
- Department of Gastroenterology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430077, China
- Laboratory of Metabolic Abnormalities and Vascular Aging Huazhong University of Science and Technology, Wuhan 430077, China
| | - Wenbo Hong
- Department of Gastroenterology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430077, China
- Laboratory of Metabolic Abnormalities and Vascular Aging Huazhong University of Science and Technology, Wuhan 430077, China
| | - Lina Xiong
- Department of Gastroenterology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430077, China
| |
Collapse
|
|
8
|
Wu M, Wu X, Han J. KIF20A Promotes CRC Progression and the Warburg Effect through the C-Myc/HIF-1α Axis. Protein Pept Lett 2024; 31:107-115. [PMID: 38037834 DOI: 10.2174/0109298665256238231120093150] [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: 05/15/2023] [Revised: 09/01/2023] [Accepted: 10/24/2023] [Indexed: 12/02/2023]
Abstract
BACKGROUND Colorectal cancer (CRC) is a prevalent form of cancer globally, characterized by a high mortality rate. Therefore, discovering effective therapeutic approaches for CRC treatment is critical. METHODS The levels of KIF20A in CRC clinical samples were determined using Western Blot and immunofluorescence assay. SW480 cells were transfected with siRNA targeting KIF20A, while HT-29 cells were transfected with a KIF20A overexpression vector. Cell viability and apoptosis of CRC cells were assessed using CCK-8 and TUNEL analysis. Migration ability was investigated using Transwell. The levels of pyruvate, lactate and ATP were determined through corresponding assay kits. Western Blot was applied to confirm the level of proteins associated with glycolysis, c- Myc, HIF-1α, PKM2 and LDHA. Subsequently, functional rescue experiments were conducted to investigate further the regulatory relationship between KIF20A, c-Myc, and HIF-1α in colorectal cancer (CRC), employing the c-Myc inhibitor 10058-F4 and c-Myc overexpression plasmids. RESULTS KIF20A was up-regulated in vivo and in vitro in CRC. KIF20A knockdown inhibited cell viability and migration while promoting cell apoptosis in SW480 cells. Conversely, overexpression of KIF20A yielded contrasting effects in HT-29 cells. Moreover, inhibition of KIF20A restrained the pyruvate, lactate production and ATP level, whereas overexpression of KIF20A enhanced the Warburg effect. Western Blot indicated that knockdown KIF20A attenuated the levels of c-Myc, HIF-1α, PKM2 and LDHA. In addition, rescue experiments further verified that KIF20A enhanced the Warburg effect by the KIF20A/c-Myc/HIF-1α axis in CRC. CONCLUSION KIF20A, being a crucial regulator in the progression of CRC, has the potential to be a promising therapeutic target for the treatment of CRC.
Collapse
Affiliation(s)
- Min Wu
- Department of Stem Cell and Regenerative Medicine, Southwest Hospital, Third Military Medical University (Army Medical University), Gaotanyan Zhengjie No. 30, Shapingba District, ChongQing, 400038, China
| | - Xianqiang Wu
- Haisco Pharmaceutical Group Company Ltd., 136 Baili Road, Wenjiang District, Chengdu, 611130, China
| | - Jie Han
- Department of General Surgery, The Third Affiliated Hospital of Chongqing Medical University, Shuanghu Branch Road No. 1, Yubei District, Chongqing, 401120, China
| |
Collapse
|
|
9
|
Di Giorgio C, Bellini R, Lupia A, Massa C, Bordoni M, Marchianò S, Rosselli R, Sepe V, Rapacciuolo P, Moraca F, Morretta E, Ricci P, Urbani G, Monti MC, Biagioli M, Distrutti E, Catalanotti B, Zampella A, Fiorucci S. Discovery of BAR502, as potent steroidal antagonist of leukemia inhibitory factor receptor for the treatment of pancreatic adenocarcinoma. Front Oncol 2023; 13:1140730. [PMID: 36998446 PMCID: PMC10043345 DOI: 10.3389/fonc.2023.1140730] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2023] [Accepted: 02/20/2023] [Indexed: 03/15/2023] Open
Abstract
IntroductionThe leukemia inhibitory factor (LIF), is a cytokine belonging to IL-6 family, whose overexpression correlate with poor prognosis in cancer patients, including pancreatic ductal adenocarcinoma (PDAC). LIF signaling is mediate by its binding to the heterodimeric LIF receptor (LIFR) complex formed by the LIFR receptor and Gp130, leading to JAK1/STAT3 activation. Bile acids are steroid that modulates the expression/activity of membrane and nuclear receptors, including the Farnesoid-X-Receptor (FXR) and G Protein Bile Acid Activated Receptor (GPBAR1).MethodsHerein we have investigated whether ligands to FXR and GPBAR1 modulate LIF/LIFR pathway in PDAC cells and whether these receptors are expressed in human neoplastic tissues. ResultsThe transcriptome analysis of a cohort of PDCA patients revealed that expression of LIF and LIFR is increased in the neoplastic tissue in comparison to paired non-neoplastic tissues. By in vitro assay we found that both primary and secondary bile acids exert a weak antagonistic effect on LIF/LIFR signaling. In contrast, BAR502 a non-bile acid steroidal dual FXR and GPBAR1 ligand, potently inhibits binding of LIF to LIFR with an IC50 of 3.8 µM.DiscussionBAR502 reverses the pattern LIF-induced in a FXR and GPBAR1 independent manner, suggesting a potential role for BAR502 in the treatment of LIFR overexpressing-PDAC.
Collapse
Affiliation(s)
| | - Rachele Bellini
- Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Antonio Lupia
- Department of Pharmacy, University of Naples Federico II, Naples, Italy
- Net4Science srl, University “Magna Græcia”, Catanzaro, Italy
| | - Carmen Massa
- Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Martina Bordoni
- Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Silvia Marchianò
- Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | | | - Valentina Sepe
- Department of Pharmacy, University of Naples Federico II, Naples, Italy
| | | | - Federica Moraca
- Department of Pharmacy, University of Naples Federico II, Naples, Italy
- Net4Science srl, University “Magna Græcia”, Catanzaro, Italy
| | - Elva Morretta
- Department of Pharmacy, University of Salerno, Salerno, Italy
| | - Patrizia Ricci
- Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Ginevra Urbani
- Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | | | - Michele Biagioli
- Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Eleonora Distrutti
- Department of Gastroenterology, Azienda Ospedaliera di Perugia, Perugia, Italy
| | - Bruno Catalanotti
- Department of Pharmacy, University of Naples Federico II, Naples, Italy
| | - Angela Zampella
- Department of Pharmacy, University of Naples Federico II, Naples, Italy
| | - Stefano Fiorucci
- Department of Medicine and Surgery, University of Perugia, Perugia, Italy
- *Correspondence: Stefano Fiorucci,
| |
Collapse
|
|
10
|
Jin Z, Peng F, Zhang C, Tao S, Xu D, Zhu Z. Expression, regulating mechanism and therapeutic target of KIF20A in multiple cancer. Heliyon 2023; 9:e13195. [PMID: 36798768 PMCID: PMC9925975 DOI: 10.1016/j.heliyon.2023.e13195] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2022] [Revised: 01/15/2023] [Accepted: 01/19/2023] [Indexed: 01/26/2023] Open
Abstract
Kinesin family member 20A (KIF20A) is a member of the kinesin family. It transports chromosomes during mitosis, plays a key role in cell division. Recently, studies proved that KIF20A was highly expressed in cancer. High expression of KIF20A was correlated with poor overall survival (OS). In this review, we summarized all the cancer that highly expressed KIF20A, described the role of KIF20A in cancer. We also organized phase I and phase II clinical trials of KIF20A peptides vaccine. All results indicated that KIF20A was a promising therapeutic target for multiple cancer.
Collapse
Key Words
- ATP, adenosine triphosphate
- BTC, biliary tract cancer
- CPC, chromosomal passenger complex
- CTL, cytotoxic T lymphocyte
- Cancer
- Cdk1, cyclin-dependent kinase 1
- DLG5, discs large MAGUK scaffold protein 5
- EMT, epithelial-mesenchymal transition
- Expression
- FoxM1, forkhead box protein M1
- GC, gastric cancer
- GEM, gemcitabine
- Gli2, glioma-associated oncogene 2
- HLA, human leukocyte antigen
- HNMT, head-and-neck malignant tumor
- IRF, interferon regulatory factor
- JAK, Janus kinase
- KIF20A
- KIF20A, kinesin family member 20A
- LP, long peptide
- MHC I, major histocompatibility complex I
- MKlp2, mitotic kinesin-like protein 2
- Mad2, mitotic arrest deficient 2
- OS, overall survival
- PBMC, peripheral blood mononuclear cell
- Plk1, polo-like kinase 1
- Regulating mechanisms
- Therapeutic target
- circRNA, circular RNA
- miRNA, microRNA
Collapse
Affiliation(s)
- Zheng Jin
- Department of Respirology & Allergy, The Third Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong Province, China
| | - Fei Peng
- Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Baylor College of Medicine, Houston, Texas, USA
| | - Chao Zhang
- Guangzhou Women and Children's Medical Center, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou Medical University, Guangzhou, Guangdong Province, China
| | - Shuang Tao
- Department of Otorhinolaryngology Head and Neck Surgery, Longgang Central Hospital of Shenzhen, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, China
| | - Damo Xu
- Department of Respirology & Allergy, The Third Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong Province, China,State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen Key Laboratory of Allergy and Immunology, Shenzhen University School of Medicine, Shenzhen, Guangdong Province, China,Corresponding author. Department of Respirology & Allergy, The Third Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong Province, China.
| | - Zhenhua Zhu
- Department of Orthopaedic Trauma, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong Province, China,Corresponding author. Department of Orthopaedic Trauma, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong Province, China.
| |
Collapse
|
|
11
|
Liu B, Su J, Fan B, Ni X, Jin T. High expression of KIF20A in bladder cancer as a potential prognostic target for poor survival of renal cell carcinoma. Medicine (Baltimore) 2023; 102:e32667. [PMID: 36637953 PMCID: PMC9839245 DOI: 10.1097/md.0000000000032667] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2022] [Accepted: 12/27/2022] [Indexed: 01/14/2023] Open
Abstract
Urinary system tumors are malignant tumors, including renal cancer and bladder cancer. however, molecular target of them remains unclear. GSE14762 and GSE53757 were downloaded from GEO database to screen differentially expressed genes (DEGs). Weighted gene co-expression network analysis was performed. Gene Ontology (GO) and Kyoto encyclopedia of genes and genomes were used for enrichment analysis. Gene ontology and Kyoto encyclopedia of genes and genomes analyses were performed on whole genome, as formulated by gene set enrichment analysis. Survival analysis was also performed. Comparative toxicogenomics database was used to identify diseases most associated with hub genes. A total of 1517 DEGs were identified. DEGs were mainly enriched in cancer pathway, HIF-1 signaling pathway, organic acid metabolism, glyoxylate and dicarboxylate metabolism, and protein homodimerization activity. Ten hub genes (TPX2, ASPM, NUSAP1, RAD51AP1, CCNA2, TTK, PBK, MELK, DTL, kinesin family member 20A [KIF20A]) were obtained, which were up-regulated in tumor tissue. The expression of KIF20A was related with the overall survival of renal and bladder cancer. KIF20A was up-regulated in the tumor tissue, and might worsen the overall survival of bladder and kidney cancer. KIF20A could be a novel biomarker of bladder and kidney cancer.
Collapse
Affiliation(s)
- Bin Liu
- Department of Urology Surgery, The Fourth Hospital of Hebei Medical University, Hebei, PR China
| | - Jianzhi Su
- Department of Urology Surgery, The Fourth Hospital of Hebei Medical University, Hebei, PR China
| | - Bo Fan
- Department of Urology Surgery, The Fourth Hospital of Hebei Medical University, Hebei, PR China
| | - Xiaochen Ni
- Department of Urology Surgery, The Fourth Hospital of Hebei Medical University, Hebei, PR China
| | - Tingting Jin
- Department of Urology Surgery, The Fourth Hospital of Hebei Medical University, Hebei, PR China
| |
Collapse
|
|
12
|
Sun D, Zhang H, Zhang C, Wang L. An evaluation of KIF20A as a prognostic factor and therapeutic target for lung adenocarcinoma using integrated bioinformatics analysis. Front Bioeng Biotechnol 2022; 10:993820. [PMID: 36619388 PMCID: PMC9816395 DOI: 10.3389/fbioe.2022.993820] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Accepted: 11/14/2022] [Indexed: 12/24/2022] Open
Abstract
The identification of prognostic and therapeutic biomarkers is essential to reduce morbidity and mortality from lung adenocarcinoma (LUAD). This study aimed to identify a reliable prognostic and therapeutic biomarker for LUAD using integrated bioinformatics. Based on the cancer genome atlas (TCGA) and genome-tissue expression (GTEx) analyses, KIF20A has been identified as the hub gene. Following validation using a series of cohorts, survival analysis, meta-analysis, and univariate Cox analysis was conducted. ESTIMATE and CIBERSORT algorithms were then used to study the association of KIF20A with the tumor microenvironment (TME) and the percentage of tumor-infiltrating immune cells (TICs). In vitro experiments were conducted to determine the function of KIF20A. Finally, there was a negative association between the expression of the KIF20A and overall survival, progression-free survival, and disease-free survival, which was confirmed by meta-analysis and COX analysis. Furthermore, KIF20A also had a potential role of altering the TME and TICs proportions in LUAD. Validations in vitro were performed on A549 and PC-9 cell lines, and we found that the knockdown of KIF20A exhibited inhibitory effects on cell proliferation, resulted in cell cycle arrest during the G2/M phase, and induced cellular apoptosis. Our study demonstrated that KIF20A could be utilized as a reliable prognostic marker and treatment target for LUAD. However, further studies are required to validate these findings.
Collapse
Affiliation(s)
- Dongjie Sun
- College of Basic Medical Sciences, Jilin University, Changchun, China
| | - Haiying Zhang
- Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin University, Changchun, China
| | - Chi Zhang
- Department of Anesthesiology, The First Hospital of Jilin University, Changchun, China
| | - Lina Wang
- Department of Pediatric Respiration, The First Hospital of Jilin University, Changchun, China,*Correspondence: Lina Wang,
| |
Collapse
|
|
13
|
Meng X, Li W, Yuan H, Dong W, Xiao W, Zhang X. KDELR2-KIF20A axis facilitates bladder cancer growth and metastasis by enhancing Golgi-mediated secretion. Biol Proced Online 2022; 24:12. [PMID: 36096734 PMCID: PMC9465899 DOI: 10.1186/s12575-022-00174-y] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Accepted: 08/23/2022] [Indexed: 11/17/2022] Open
Abstract
Background Bladder cancer (BCa) is a fatal form of cancer worldwide associated with a poor prognosis. Identifying novel drivers of growth and metastasis hold therapeutic potential for the disease. Transport homeostasis between the endoplasmic reticulum and Golgi and the secretion of matrix metalloproteinases (MMPs) mediated by Golgi have been reported to be closely associated with tumor progression. However, to date, mechanistic studies remain limited. Results Here, we identified KDELR2 as a potential risk factor with prognostic value in patients with BCa, especially those harbouring the KDELR2 amplification. In addition, we found that KDELR2 is a regulator of BCa cell proliferation and tumorigenicity based on bioinformatic analysis with functional studies. Mechanistically, we revealed that KDELR2 could regulate the expression of KIF20A, thus stimulating the expression of MMP2, MMP9 and MKI67. Functionally, the overexpression of KDELR2 and KIF20A markedly promoted proliferation, migration, and invasion in vitro and enhanced tumor growth in vivo, while knockdown of KDELR2 and KIF20A exerted the opposite effects. And the overexpression of KDELR2 also enhanced lymph node metastasis in vivo. Conclusions Collectively, our findings clarified a hitherto unexplored mechanism of KDELR2-KIF20A axis in increasing Golgi-mediated secretion of MMPs to drive tumor progression in BCa. Supplementary Information The online version contains supplementary material available at 10.1186/s12575-022-00174-y.
Collapse
Affiliation(s)
- Xiangui Meng
- Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.,Shenzhen Huazhong University of Science and Technology Research Institute, Shenzhen, 518000, China.,Institute of Urology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Weiquan Li
- Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.,Shenzhen Huazhong University of Science and Technology Research Institute, Shenzhen, 518000, China.,Institute of Urology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Hongwei Yuan
- Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.,Shenzhen Huazhong University of Science and Technology Research Institute, Shenzhen, 518000, China.,Institute of Urology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Wei Dong
- Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. .,Shenzhen Huazhong University of Science and Technology Research Institute, Shenzhen, 518000, China. .,Institute of Urology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
| | - Wen Xiao
- Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. .,Shenzhen Huazhong University of Science and Technology Research Institute, Shenzhen, 518000, China. .,Institute of Urology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
| | - Xiaoping Zhang
- Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. .,Shenzhen Huazhong University of Science and Technology Research Institute, Shenzhen, 518000, China. .,Institute of Urology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
| |
Collapse
|
|
14
|
Yu Z, Liang C, Tu H, Qiu S, Dong X, Zhang Y, Ma C, Li P. Common Core Genes Play Vital Roles in Gastric Cancer With Different Stages. Front Genet 2022; 13:881948. [PMID: 35938042 PMCID: PMC9352954 DOI: 10.3389/fgene.2022.881948] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2022] [Accepted: 05/31/2022] [Indexed: 12/24/2022] Open
Abstract
Background: Owing to complex molecular mechanisms in gastric cancer (GC) oncogenesis and progression, existing biomarkers and therapeutic targets could not significantly improve diagnosis and prognosis. This study aims to identify the key genes and signaling pathways related to GC oncogenesis and progression using bioinformatics and meta-analysis methods. Methods: Eligible microarray datasets were downloaded and integrated using the meta-analysis method. According to the tumor stage, GC gene chips were classified into three groups. Thereafter, the three groups’ differentially expressed genes (DEGs) were identified by comparing the gene data of the tumor groups with those of matched normal specimens. Enrichment analyses were conducted based on common DEGs among the three groups. Then protein–protein interaction (PPI) networks were constructed to identify relevant hub genes and subnetworks. The effects of significant DEGs and hub genes were verified and explored in other datasets. In addition, the analysis of mutated genes was also conducted using gene data from The Cancer Genome Atlas database. Results: After integration of six microarray datasets, 1,229 common DEGs consisting of 1,065 upregulated and 164 downregulated genes were identified. Alpha-2 collagen type I (COL1A2), tissue inhibitor matrix metalloproteinase 1 (TIMP1), thymus cell antigen 1 (THY1), and biglycan (BGN) were selected as significant DEGs throughout GC development. The low expression of ghrelin (GHRL) is associated with a high lymph node ratio (LNR) and poor survival outcomes. Thereafter, we constructed a PPI network of all identified DEGs and gained 39 subnetworks and the top 20 hub genes. Enrichment analyses were performed for common DEGs, the most related subnetwork, and the top 20 hub genes. We also selected 61 metabolic DEGs to construct PPI networks and acquired the relevant hub genes. Centrosomal protein 55 (CEP55) and POLR1A were identified as hub genes associated with survival outcomes. Conclusion: The DEGs, hub genes, and enrichment analysis for GC with different stages were comprehensively investigated, which contribute to exploring the new biomarkers and therapeutic targets.
Collapse
Affiliation(s)
- Zhiyuan Yu
- School of Medicine, Nankai University, Tianjin, China
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Chen Liang
- First Department of Liver Disease / Beijing Municipal Key Laboratory of Liver Failure and Artificial Liver Treatment Research, Beijing You’an Hospital, Capital Medical University, Beijing, China
| | - Huaiyu Tu
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Shuzhong Qiu
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Xiaoyu Dong
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Yonghui Zhang
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Chao Ma
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Peiyu Li
- School of Medicine, Nankai University, Tianjin, China
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing, China
- *Correspondence: Peiyu Li,
| |
Collapse
|
|
15
|
Genistein: Therapeutic and Preventive Effects, Mechanisms, and Clinical Application in Digestive Tract Tumor. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:5957378. [PMID: 35815271 PMCID: PMC9259214 DOI: 10.1155/2022/5957378] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/05/2022] [Accepted: 05/28/2022] [Indexed: 12/30/2022]
Abstract
Genistein is one of the numerous recognized isoflavones that may be found in a variety of soybeans and soy products, including tofu and tofu products. The chemical name for genistein is 4', 5, 7-trihydroxyisoflavone, and it is found in plants. In recent years, the scientific world has become more interested in genistein because of its possible therapeutic effects on many forms of cancer. It has been widely investigated for its anticancer properties. The discovery of genistein's mechanism of action indicates its potential for apoptosis induction and cell cycle arrest in gastrointestinal cancer, especially gastric and colorectal cancer. Genistein's pharmacological activities as determined by the experimental studies presented in this review lend support to its use in the treatment of gastrointestinal cancer; however, additional research is needed in the future to determine its efficacy, safety, and the potential for using nanotechnology to increase bioavailability and therapeutic efficacy.
Collapse
|
|
16
|
Liang B, Zhou Y, Jiao J, Xu L, Yan Y, Wu Q, Tong X, Yan H. Integrated Analysis of Transcriptome Data Revealed AURKA and KIF20A as Critical Genes in Medulloblastoma Progression. Front Oncol 2022; 12:875521. [PMID: 35574421 PMCID: PMC9092218 DOI: 10.3389/fonc.2022.875521] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Accepted: 03/29/2022] [Indexed: 12/03/2022] Open
Abstract
Medulloblastoma is the neuroepithelial tumor with the highest degree of malignancy in the central nervous system, accounting for about 8% to 10% of children’s brain tumors. It has a high degree of malignancy and is easily transmitted through cerebrospinal fluid, with a relatively poor prognosis. Although medulloblastoma has been widely studied and treated, its molecular mechanism remains unclear. To determine which gene plays a crucial role in medulloblastoma development and progression, we analyzed three microarray datasets from Gene Expression Omnibus. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were used to detect and evaluate differentially expressed genes. Protein interaction network was established, and the hub genes were determined in cytoHubba through various assessment methods, while the target genes were screened out using survival analysis. Ultimately, human medulloblastoma samples were utilized to confirm target gene expression. In conclusion, This study found that aurora kinase A (AURKA) and kinesin family member 20A (KIF20A) may be involved in the initiation and development of medulloblastoma, have a close association with prognosis, and may become a potential therapeutic target and prognostic marker of MED.
Collapse
Affiliation(s)
- Bo Liang
- Clinical College of Neurology, Neurosurgery and Neurorehabilitation, Tianjin Medical University, Tianjin, China.,Department of Neurosurgery, The Fifith Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yan Zhou
- Clinical College of Neurology, Neurosurgery and Neurorehabilitation, Tianjin Medical University, Tianjin, China
| | - Jiji Jiao
- Clinical College of Neurology, Neurosurgery and Neurorehabilitation, Tianjin Medical University, Tianjin, China
| | - Lixia Xu
- Tianjin Neurosurgical Institute, Tianjin Key Laboratory of Cerebrovascular and Neurodegenerative Diseases, Tianjin Huanhu Hospital, Tianjin, China
| | - Yan Yan
- Clinical Laboratory, Tianjin Huanhu Hospital, Tianjin, China
| | - Qiaoli Wu
- Tianjin Neurosurgical Institute, Tianjin Key Laboratory of Cerebrovascular and Neurodegenerative Diseases, Tianjin Huanhu Hospital, Tianjin, China
| | - Xiaoguang Tong
- Tianjin Neurosurgical Institute, Tianjin Key Laboratory of Cerebrovascular and Neurodegenerative Diseases, Tianjin Huanhu Hospital, Tianjin, China.,Department of Neurosurgery, Tianjin Huanhu Hospital, Tianjin, China
| | - Hua Yan
- Tianjin Neurosurgical Institute, Tianjin Key Laboratory of Cerebrovascular and Neurodegenerative Diseases, Tianjin Huanhu Hospital, Tianjin, China.,Department of Neurosurgery, Tianjin Huanhu Hospital, Tianjin, China
| |
Collapse
|
|
17
|
LncRNA ARAP1-AS1 Promotes Bladder Cancer Development by Regulating the miR-3918/KIF20A Axis. Mol Biotechnol 2022; 64:1259-1269. [PMID: 35556220 DOI: 10.1007/s12033-022-00489-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2021] [Accepted: 03/31/2022] [Indexed: 12/24/2022]
Abstract
This study is to clarify the effect of the long non-coding RNA ArfGAP with RhoGAP domain, ankyrin repeat and PH domain 1-antisense RNA 1 (ARAP1-AS1)/microRNA (miR)-3918/kinesin family member 20A (KIF20A) on bladder cancer cell function. ARAP1-AS1, miR-3918, and KIF20A expression levels in bladder cancer cells were determined using quantitative reverse transcription-polymerase chain reaction. The effects of ARAP1-AS1, miR-3918, and KIF20A on bladder cell activity, proliferation, apoptosis, and in vivo growth were examined using the cell counting kit-8, colony formation, caspase-3 activity, and xenograft tumor growth assays, respectively, in nude mice. The binding relationships among ARAP1-AS1, miR-3918, and KIF20A were analyzed using luciferase and RNA immunoprecipitation assays. ARAP1-AS1 and KIF20A were overexpressed in bladder cancer, while miR-3918 was underexpressed. The downregulation of ARAP1-AS1 or KIF20A expression significantly inhibited the viability and proliferation of cancer cells and promoted apoptosis, whereas low expression of miR-3918 or high expression of ARAP1-AS1/KIF20A showed the opposite effect. miR-3918 was sponged by ARAP1-AS1, and targeted KIF20A. In addition, miR-3918 expression was inversely correlated with ARAP1-AS1 and KIF20a expression levels in bladder cancer tissues. In addition, the rescue experiment showed that interference with miR-3918 could reverse the effect of low ARAP1-AS1 or KIF20A expression on bladder cancer cell malignancy. ARAP1-AS1 facilitates the malignant behavior of bladder cancer cells via the regulation of KIF20A expression by sponging miR-3918.
Collapse
|
|
18
|
Disruption of the CCDC43-FHL1 interaction triggers apoptosis in gastric cancer cells. Exp Cell Res 2022; 415:113107. [DOI: 10.1016/j.yexcr.2022.113107] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2021] [Revised: 03/09/2022] [Accepted: 03/11/2022] [Indexed: 11/18/2022]
|
|
19
|
Zeng Z, Zhang X, Jiang CQ, Zhang YG, Wu X, Li J, Tang S, Li L, Gu LJ, Xie XY, Jiang YA. Identifying novel therapeutic targets in gastric cancer using genome-wide CRISPR-Cas9 screening. Oncogene 2022; 41:2069-2078. [PMID: 35177812 DOI: 10.1038/s41388-022-02177-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Revised: 12/15/2021] [Accepted: 01/04/2022] [Indexed: 12/18/2022]
Abstract
Genome-scale CRISPR-Cas9 screening technology is a powerful tool to systematically identify genes essential for cancer cell survival. Herein, TKOv3, a genome-scale CRISPR-Cas9 knock-out library, was screened in the gastric cancer (GC) cells, and relevant validation experiments were performed. We obtained 854 essential genes for the AGS cell line, and 184 were novel essential genes. After knocking down essential genes: SPC25, DHX37, ABCE1, SNRPB, TOP3A, RUVBL1, CIT, TACC3 and MTBP, cell viability and proliferation were significantly decreased. Then, we analysed the detected essential genes at different time points and proved more characteristic genes might appear with the extension of selection. After progressive selection using a series of open datasets, 41 essential genes were identified as potential drug targets. Among them, methyltransferase 1 (METTL1) was over expressed in GC tissues. High METTL1 expression was associated with poor prognosis among 3 of 6 GC cohorts. Furthermore, GC cells growth was significantly inhibited after the down-regulation of METTL1 in vitro and in vivo. Function analysis revealed that METTL1 might play a role in the cell cycle through AKT/STAT3 pathways. In conclusion, compared with existing genome-scale screenings, we obtained 184 novel essential genes. Among them, METTL1 was validated as a potential therapeutic target of GC.
Collapse
Affiliation(s)
- Zhi Zeng
- Department of Pathology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Xu Zhang
- Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Cong-Qing Jiang
- Department of Colorectal and Anal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
| | - Yong-Gang Zhang
- Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Xue Wu
- Department of Biomedical informatics, The Ohio State University, Columbus, OH, USA
| | - Jin Li
- Department of Biomedical informatics, The Ohio State University, Columbus, OH, USA
| | - Shan Tang
- Department of Biomedical informatics, The Ohio State University, Columbus, OH, USA
| | - Lang Li
- Department of Biomedical informatics, The Ohio State University, Columbus, OH, USA
| | - Li-Juan Gu
- Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Xiao-Yu Xie
- Department of Colorectal and Anal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.
| | - Ying-An Jiang
- Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
| |
Collapse
|
|
20
|
Liu H, Chen C, Fehm T, Cheng Z, Neubauer H. Identifying Mitotic Kinesins as Potential Prognostic Biomarkers in Ovarian Cancer Using Bioinformatic Analyses. Diagnostics (Basel) 2022; 12:470. [PMID: 35204562 PMCID: PMC8871464 DOI: 10.3390/diagnostics12020470] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Revised: 02/03/2022] [Accepted: 02/08/2022] [Indexed: 02/01/2023] Open
Abstract
Ovarian cancer (OC) is characterized by late-stage presentation, chemoresistance, and poor survival. Evaluating the prognosis of OC patients via effective biomarkers is essential to manage OC progression and to improve survival; however, it has been barely established. Here, we intend to identify differentially expressed genes (DEGs) as potential prognostic biomarkers of OC via bioinformatic analyses. Initially, a total of thirteen DEGs were extracted from different public databases as candidates. The expression of KIF20A, one of the DEGs, was correlated with a worse outcome of OC patients. The functional correlation of the DEGs with mitosis and the prognostic value of KIF20A imply a high correlation between mitotic kinesins (KIFs) and OC development. Finally, we found that KIF20A, together with the other nine mitotic KIFs (4A, 11, 14, 15, 18A, 18B, 23, C1, and2C) were upregulated and activated in OC tissues. Among the ten, seven overexpressed mitotic KIFs (11, 14, 18B, 20A, 23, and C1) were correlated with unfavorable clinical prognosis. Moreover, KIF20A and KIF23 overexpression was associated with worse prognosis in OC patients treated with platinum/taxol chemotherapy, while OCs overexpressing mitotic KIFs (11, 15, 18B, and C1) were resistant to MAPK pathway inhibitors. In conclusion, worse outcomes of OC patients were correlated with overexpression of several mitotic KIFs, which may serve both as prognostic biomarkers and therapeutic targets for OC.
Collapse
Affiliation(s)
- Hailun Liu
- Department of Obstetrics and Gynecology, University Hospital and Medical Faculty of the Heinrich-Heine University Duesseldorf, Universitaetsstr, 1, 40225 Duesseldorf, Germany; (H.L.); (C.C.); (T.F.)
- Department of Obstetrics and Gynecology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China
| | - Chen Chen
- Department of Obstetrics and Gynecology, University Hospital and Medical Faculty of the Heinrich-Heine University Duesseldorf, Universitaetsstr, 1, 40225 Duesseldorf, Germany; (H.L.); (C.C.); (T.F.)
- Breast and Thyroid Center, The First People’s Hospital of Zunyi (The Third Affiliated Hospital of Zunyi Medical University), Zunyi 563000, China
| | - Tanja Fehm
- Department of Obstetrics and Gynecology, University Hospital and Medical Faculty of the Heinrich-Heine University Duesseldorf, Universitaetsstr, 1, 40225 Duesseldorf, Germany; (H.L.); (C.C.); (T.F.)
| | - Zhongping Cheng
- Department of Obstetrics and Gynecology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China
- Institute of Gynecological Minimally Invasive Medicine, Tongji University School of Medicine, Shanghai 200072, China
| | - Hans Neubauer
- Department of Obstetrics and Gynecology, University Hospital and Medical Faculty of the Heinrich-Heine University Duesseldorf, Universitaetsstr, 1, 40225 Duesseldorf, Germany; (H.L.); (C.C.); (T.F.)
| |
Collapse
|
|
21
|
Chen JC, Xie TA, Lin ZZ, Li YQ, Xie YF, Li ZW, Guo XG. Identification of Key Pathways and Genes in SARS-CoV-2 Infecting Human Intestines by Bioinformatics Analysis. Biochem Genet 2021; 60:1076-1094. [PMID: 34787756 PMCID: PMC8596852 DOI: 10.1007/s10528-021-10144-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Accepted: 10/21/2021] [Indexed: 12/20/2022]
Abstract
COVID-19 is a serious infectious disease that has recently swept the world, and research on its causative virus, SARS-CoV-2, remains insufficient. Therefore, this study uses bioinformatics analysis techniques to explore the human digestive tract diseases that may be caused by SARS-CoV-2 infection. The gene expression profile data set, numbered GSE149312, is from the Gene Expression Omnibus (GEO) database and is divided into a 24-h group and a 60-h group. R software is used to analyze and screen out differentially expressed genes (DEGs) and then gene ontology (GO) term and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses are performed. In KEGG, the pathway of non-alcoholic fatty liver disease exists in both the 24-h group and 60-h group. STRING is used to establish a protein–protein interaction (PPI) network, and Cytoscape is then used to visualize the PPI and define the top 12 genes of the node as the hub genes. Through verification, nine statistically significant hub genes are identified: AKT1, TIMP1, NOTCH, CCNA2, RRM2, TTK, BUB1B, KIF20A, and PLK1. In conclusion, the results of this study can provide a certain direction and basis for follow-up studies of SARS-CoV-2 infection of the human digestive tract and provide new insights for the prevention and treatment of diseases caused by SARS-CoV-2.
Collapse
Affiliation(s)
- Ji-Chun Chen
- Department of Clinical Medicine, The Third Clinical School of Guangzhou Medical University, Guangzhou, 510150, China
| | - Tian-Ao Xie
- Department of Clinical Medicine, The Third Clinical School of Guangzhou Medical University, Guangzhou, 510150, China
| | - Zhen-Zong Lin
- Department of Clinical Medicine, The Third Clinical School of Guangzhou Medical University, Guangzhou, 510150, China
| | - Yi-Qing Li
- Department of Clinical Medicine, The Third Clinical School of Guangzhou Medical University, Guangzhou, 510150, China
| | - Yu-Fei Xie
- Department of Clinical Medicine, The Third Clinical School of Guangzhou Medical University, Guangzhou, 510150, China
| | - Zhong-Wei Li
- Department of Clinical Medicine, The Third Clinical School of Guangzhou Medical University, Guangzhou, 510150, China
| | - Xu-Guang Guo
- Department of Clinical Medicine, The Third Clinical School of Guangzhou Medical University, Guangzhou, 510150, China. .,Department of Clinical Laboratory Medicine, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China. .,Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China. .,Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China.
| |
Collapse
|
|
22
|
Depletion of kinesin motor KIF20A to target cell fate control suppresses medulloblastoma tumour growth. Commun Biol 2021; 4:552. [PMID: 33976373 PMCID: PMC8113472 DOI: 10.1038/s42003-021-02075-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Accepted: 04/01/2021] [Indexed: 11/09/2022] Open
Abstract
During mammalian brain development, neural progenitor cells proliferate extensively but can ensure the production of correct numbers of various types of mature cells by balancing symmetric proliferative versus asymmetric differentiative cell divisions. This process of cell fate determination may be harnessed for developing cancer therapy. Here, we test this idea by targeting KIF20A, a mitotic kinesin crucial for the control of cell division modes, in a genetic model of medulloblastoma (MB) and human MB cells. Inducible Kif20a knockout in both normal and MB-initiating granule neuron progenitors (GNPs) causes early cell cycle exit and precocious neuronal differentiation without causing cytokinesis failure and suppresses the development of Sonic Hedgehog (SHH)-activated MB. Inducible KIF20A knockdown in human MB cells inhibits proliferation both in cultures and in growing tumors. Our results indicate that targeting the fate specification process of nascent daughter cells presents a novel avenue for developing anti-proliferation treatment for malignant brain tumors. Runxiang Qiu et al find that conditional knockout of Kif20a, a regulator of cytokinesis and neural progenitor cell fate, induces early cell cycle exit and precocious neuronal differentiation of cerebellar granule neuron progenitors. They show that Kif20a depletion suppresses tumour formation in genetic and xenograft mouse models of medulloblastoma, indicating the value of targeting daughter cell fate specification.
Collapse
|
|
23
|
Xing Q, Zeng T, Liu S, Cheng H, Ma L, Wang Y. A novel 10 glycolysis-related genes signature could predict overall survival for clear cell renal cell carcinoma. BMC Cancer 2021; 21:381. [PMID: 33836688 PMCID: PMC8034085 DOI: 10.1186/s12885-021-08111-0] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2020] [Accepted: 03/28/2021] [Indexed: 02/07/2023] Open
Abstract
Background The role of glycolysis in tumorigenesis has received increasing attention and multiple glycolysis-related genes (GRGs) have been proven to be associated with tumor metastasis. Hence, we aimed to construct a prognostic signature based on GRGs for clear cell renal cell carcinoma (ccRCC) and to explore its relationships with immune infiltration. Methods Clinical information and RNA-sequencing data of ccRCC were obtained from The Cancer Genome Atlas (TCGA) and ArrayExpress datasets. Key GRGs were finally selected through univariate COX, LASSO and multivariate COX regression analyses. External and internal verifications were further carried out to verify our established signature. Results Finally, 10 GRGs including ANKZF1, CD44, CHST6, HS6ST2, IDUA, KIF20A, NDST3, PLOD2, VCAN, FBP1 were selected out and utilized to establish a novel signature. Compared with the low-risk group, ccRCC patients in high-risk groups showed a lower overall survival (OS) rate (P = 5.548Ee-13) and its AUCs based on our established signature were all above 0.70. Univariate/multivariate Cox regression analyses further proved that this signature could serve as an independent prognostic factor (all P < 0.05). Moreover, prognostic nomograms were also created to find out the associations between the established signature, clinical factors and OS for ccRCC in both the TCGA and ArrayExpress cohorts. All results remained consistent after external and internal verification. Besides, nine out of 21 tumor-infiltrating immune cells (TIICs) were highly related to high- and low- risk ccRCC patients stratified by our established signature. Conclusions A novel signature based on 10 prognostic GRGs was successfully established and verified externally and internally for predicting OS of ccRCC, helping clinicians better and more intuitively predict patients’ survival. Supplementary Information The online version contains supplementary material available at 10.1186/s12885-021-08111-0.
Collapse
Affiliation(s)
- Qianwei Xing
- Department of Urology, Affiliated Hospital of Nantong University, No.20 West Temple Road, Nantong, Jiangsu Province, 226001, China
| | - Tengyue Zeng
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, 210029, China
| | - Shouyong Liu
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, 210029, China
| | - Hong Cheng
- Department of Urology, Zhongda Hospital Affiliated to Southeast University, Nanjing, 210009, China
| | - Limin Ma
- Department of Urology, Affiliated Hospital of Nantong University, No.20 West Temple Road, Nantong, Jiangsu Province, 226001, China.
| | - Yi Wang
- Department of Urology, Affiliated Hospital of Nantong University, No.20 West Temple Road, Nantong, Jiangsu Province, 226001, China.
| |
Collapse
|
|
24
|
Chang X, Li D, Liu C, Zhang Z, Wang T. Pentraxin 3 is a diagnostic and prognostic marker for ovarian epithelial cancer patients based on comprehensive bioinformatics and experiments. Cancer Cell Int 2021; 21:193. [PMID: 33952272 PMCID: PMC8097951 DOI: 10.1186/s12935-021-01854-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Revised: 02/20/2021] [Accepted: 02/24/2021] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Ovarian epithelial cancer is one of the leading malignant tumors in gynecology and lacks effective diagnostic and prognostic markers. Our study aims to screen and verify ovarian epithelial cancer biomarkers. METHODS GSE18520 and GSE26712 were downloaded from the GEO database. The "limma" and "WGCNA" packages were used to explore hub genes. The Kaplan-Meier Plotter database was used for survival analysis of the hub genes. Immunohistochemical analysis was used to identify the expression level of Pentraxin 3 in ovarian epithelial cancer samples. RESULTS In this study, we integrated and analyzed two datasets, GSE18520 and GSE26712, and a total of 238 differentially expressed genes (DEGs) were screened out. Enrichment analysis showed that these DEGs were related to collagen-containing extracellular matrix and other pathways. Further application of WGCNA (weighted gene coexpression network analysis) identified 15 gene modules, with the purple module showing the highest correlation with ovarian epithelial cancer. Twenty-five genes were shared between the purple module and DEGs, 13 genes were related to the prognosis of ovarian epithelial cancer patients, and the PTX3 gene had the highest hazardous risk (HR) value. We performed immunohistochemical analyses on the 255 Pentraxin-3 (PTX3)-based clinical samples. PTX3 was found to be overexpressed in ovarian epithelial cancer and related to the degree of differentiation. The Cox proportional hazard model indicates that high PTX3 expression is an independent risk factor for the prognosis of ovarian epithelial cancer patients. CONCLUSIONS In conclusion, through WGCNA and a series of comprehensive bioinformatics analyses, PTX3 was first identified as a novel diagnostic and prognostic biomarker for ovarian epithelial cancer.
Collapse
Affiliation(s)
- Xiaoying Chang
- Department of Pathology, Shengjing Hospital of China Medical University, 36 Sanhao Street, Heping, Shenyang, 110004, China
| | - Dan Li
- Department of Pathology, Shengjing Hospital of China Medical University, 36 Sanhao Street, Heping, Shenyang, 110004, China
| | - Chang Liu
- Department of Pathology, Shengjing Hospital of China Medical University, 36 Sanhao Street, Heping, Shenyang, 110004, China
| | - Zhe Zhang
- Department of Pathology, Shengjing Hospital of China Medical University, 36 Sanhao Street, Heping, Shenyang, 110004, China
| | - Tao Wang
- Department of Pathology, Shenyang KingMed Center for Clinical Laboratory Co., Ltd, Shenyang, 110164, China.
| |
Collapse
|
|
25
|
Yang C, Zhang Y, Lin S, Liu Y, Li W. Suppressing the KIF20A/NUAK1/Nrf2/GPX4 signaling pathway induces ferroptosis and enhances the sensitivity of colorectal cancer to oxaliplatin. Aging (Albany NY) 2021; 13:13515-13534. [PMID: 33819186 PMCID: PMC8202845 DOI: 10.18632/aging.202774] [Citation(s) in RCA: 103] [Impact Index Per Article: 25.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2019] [Accepted: 12/18/2020] [Indexed: 04/11/2023]
Abstract
Oxaliplatin resistance can develop in colorectal cancer (CRC), which may involve inhibition of ferroptosis, although further research is needed to understand this potential mechanism. We evaluated CRC cells with acquired oxaliplatin resistance (HCT116-Or) or congenital resistance (H716) to determine whether a ferroptosis inducer (RSL3) or inhibitor (liproxstatin-1) could modulate the effects of oxaliplatin. The results suggested that induction of ferroptosis could significantly reverse the oxaliplatin resistance of the CRC cells. Bioinformatic and cytobiological searches also revealed that KIF20A was highly expressed in the oxaliplatin-resistant cell lines and was strongly correlated with survival among CRC patients. Silencing KIF20A enhanced cellular sensitivity to oxaliplatin both in vivo and in vitro, and silencing KIF20A also suppressed NUAK1 activation, while a NUAK1 agonist (ETC-1002) could reverse the oxaliplatin sensitivity of KIF20A-silenced cells. Moreover, silencing NUAK1 up-regulated the expression of PP1β, down-regulated the phosphorylation of downstream GSK3βSer9, suppressed the nuclear import of Nrf2, inhibited the expression of a ferroptosis key negative regulatory protein (GPX4), and blocked cellular resistance. Applying a Nrf2 agonist (oltipraz) also reversed the oxaliplatin sensitivity of NUAK1-silenced cells. Therefore, cellular ferroptosis may be inhibited via the KIF20A/NUAK1/PP1β/GPX4 pathway in CRC cells, which may underly the resistance of CRC to oxaliplatin.
Collapse
Affiliation(s)
- Changshun Yang
- Department of Surgical Oncology, Fujian Provincial Hospital, Fuzhou 350001, China
| | - Yu Zhang
- Department of Pathology, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350001, China
| | - Shengtao Lin
- Department of Surgical Oncology, Fujian Provincial Hospital, Fuzhou 350001, China
| | - Yi Liu
- Department of Endoscopy, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100000, China
| | - Weihua Li
- Department of Surgical Oncology, Fujian Provincial Hospital, Fuzhou 350001, China
| |
Collapse
|
|
26
|
Hao W, Zhao H, Li Z, Li J, Guo J, Chen Q, Gao Y, Ren M, Zhao X, Yue W. Identification of potential markers for differentiating epithelial ovarian cancer from ovarian low malignant potential tumors through integrated bioinformatics analysis. J Ovarian Res 2021; 14:46. [PMID: 33726773 PMCID: PMC7968266 DOI: 10.1186/s13048-021-00794-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2020] [Accepted: 03/05/2021] [Indexed: 01/10/2023] Open
Abstract
Background Epithelial ovarian cancer (EOC), as a lethal malignancy in women, is often diagnosed as advanced stages. In contrast, intermediating between benign and malignant tumors, ovarian low malignant potential (LMP) tumors show a good prognosis. However, the differential diagnosis of the two diseases is not ideal, resulting in delays or unnecessary therapies. Therefore, unveiling the molecular differences between LMP and EOC may contribute to differential diagnosis and novel therapeutic and preventive policies development for EOC. Methods In this study, three microarray data (GSE9899, GSE57477 and GSE27651) were used to explore the differentially expressed genes (DEGs) between LMP and EOC samples. Then, 5 genes were screened by protein–protein interaction (PPI) network, receiver operating characteristic (ROC), survival and Pearson correlation analysis. Meanwhile, chemical-core gene network construction was performed to identify the potential drugs or risk factors for EOC based on 5 core genes. Finally, we also identified the potential function of the 5 genes for EOC through pathway analysis. Results Two hundred thirty-four DEGs were successfully screened, including 81 up-regulated genes and 153 down-regulated genes. Then, 5 core genes (CCNB1, KIF20A, ASPM, AURKA, and KIF23) were identified through PPI network analysis, ROC analysis, survival and Pearson correlation analysis, which show better diagnostic efficiency and higher prognostic value for EOC. Furthermore, NetworkAnalyst was used to identify top 15 chemicals that link with the 5 core genes. Among them, 11 chemicals were potential drugs and 4 chemicals were risk factors for EOC. Finally, we found that all 5 core genes mainly regulate EOC development via the cell cycle pathway by the bioinformatic analysis. Conclusion Based on an integrated bioinformatic analysis, we identified potential biomarkers, risk factors and drugs for EOC, which may help to provide new ideas for EOC diagnosis, condition appraisal, prevention and treatment in future. Supplementary Information The online version contains supplementary material available at 10.1186/s13048-021-00794-0.
Collapse
Affiliation(s)
- Wende Hao
- Central Laboratory, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, 100026, China
| | - Hongyu Zhao
- Central Laboratory, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, 100026, China
| | - Zhefeng Li
- Central Laboratory, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, 100026, China
| | - Jie Li
- Central Laboratory, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, 100026, China
| | - Jiahao Guo
- Central Laboratory, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, 100026, China
| | - Qi Chen
- Central Laboratory, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, 100026, China
| | - Yan Gao
- Central Laboratory, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, 100026, China
| | - Meng Ren
- Central Laboratory, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, 100026, China
| | - Xiaoting Zhao
- Central Laboratory, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, 100026, China.
| | - Wentao Yue
- Central Laboratory, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, 100026, China.
| |
Collapse
|
|
27
|
Kader A, Brangsch J, Kaufmann JO, Zhao J, Mangarova DB, Moeckel J, Adams LC, Sack I, Taupitz M, Hamm B, Makowski MR. Molecular MR Imaging of Prostate Cancer. Biomedicines 2020; 9:1. [PMID: 33375045 PMCID: PMC7822017 DOI: 10.3390/biomedicines9010001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Revised: 12/18/2020] [Accepted: 12/19/2020] [Indexed: 02/06/2023] Open
Abstract
This review summarizes recent developments regarding molecular imaging markers for magnetic resonance imaging (MRI) of prostate cancer (PCa). Currently, the clinical standard includes MR imaging using unspecific gadolinium-based contrast agents. Specific molecular probes for the diagnosis of PCa could improve the molecular characterization of the tumor in a non-invasive examination. Furthermore, molecular probes could enable targeted therapies to suppress tumor growth or reduce the tumor size.
Collapse
Affiliation(s)
- Avan Kader
- Department of Radiology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany; (J.B.); (J.O.K.); (J.Z.); (D.B.M.); (J.M.); (L.C.A.); (I.S.); (M.T.); (B.H.); (M.R.M.)
- Department of Biology, Chemistry and Pharmacy, Institute of Biology, Freie Universität Berlin, Königin-Luise-Str. 1-3, 14195 Berlin, Germany
| | - Julia Brangsch
- Department of Radiology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany; (J.B.); (J.O.K.); (J.Z.); (D.B.M.); (J.M.); (L.C.A.); (I.S.); (M.T.); (B.H.); (M.R.M.)
- Department of Veterinary Medicine, Institute of Animal Welfare, Animal Behavior and Laboratory Animal Science, Freie Universität Berlin, Königsweg 67, Building 21, 14163 Berlin, Germany
| | - Jan O. Kaufmann
- Department of Radiology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany; (J.B.); (J.O.K.); (J.Z.); (D.B.M.); (J.M.); (L.C.A.); (I.S.); (M.T.); (B.H.); (M.R.M.)
- Division 1.5 Protein Analysis, Federal Institute for Materials Research and Testing (BAM), Richard-Willstätter-Str. 11, 12489 Berlin, Germany
- Department of Chemistry, Humboldt-Universität zu Berlin, Brook-Taylor-Str. 2, 12489 Berlin, Germany
| | - Jing Zhao
- Department of Radiology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany; (J.B.); (J.O.K.); (J.Z.); (D.B.M.); (J.M.); (L.C.A.); (I.S.); (M.T.); (B.H.); (M.R.M.)
| | - Dilyana B. Mangarova
- Department of Radiology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany; (J.B.); (J.O.K.); (J.Z.); (D.B.M.); (J.M.); (L.C.A.); (I.S.); (M.T.); (B.H.); (M.R.M.)
- Department of Veterinary Medicine, Institute of Veterinary Pathology, Freie Universität Berlin, Robert-von-Ostertag-Str. 15, Building 12, 14163 Berlin, Germany
| | - Jana Moeckel
- Department of Radiology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany; (J.B.); (J.O.K.); (J.Z.); (D.B.M.); (J.M.); (L.C.A.); (I.S.); (M.T.); (B.H.); (M.R.M.)
| | - Lisa C. Adams
- Department of Radiology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany; (J.B.); (J.O.K.); (J.Z.); (D.B.M.); (J.M.); (L.C.A.); (I.S.); (M.T.); (B.H.); (M.R.M.)
| | - Ingolf Sack
- Department of Radiology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany; (J.B.); (J.O.K.); (J.Z.); (D.B.M.); (J.M.); (L.C.A.); (I.S.); (M.T.); (B.H.); (M.R.M.)
| | - Matthias Taupitz
- Department of Radiology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany; (J.B.); (J.O.K.); (J.Z.); (D.B.M.); (J.M.); (L.C.A.); (I.S.); (M.T.); (B.H.); (M.R.M.)
| | - Bernd Hamm
- Department of Radiology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany; (J.B.); (J.O.K.); (J.Z.); (D.B.M.); (J.M.); (L.C.A.); (I.S.); (M.T.); (B.H.); (M.R.M.)
| | - Marcus R. Makowski
- Department of Radiology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany; (J.B.); (J.O.K.); (J.Z.); (D.B.M.); (J.M.); (L.C.A.); (I.S.); (M.T.); (B.H.); (M.R.M.)
- School of Biomedical Engineering and Imaging Sciences, King’s College London, St Thomas’ Hospital Westminster Bridge Road, London SE1 7EH, UK
- Department of Diagnostic and Interventional Radiology, School of Medicine & Klinikum Rechts der Isar, Technical University of Munich, Munich (TUM), Ismaninger Str. 22, 81675 München, Germany
| |
Collapse
|
|
28
|
Liu X, Yin M, Liu X, Da J, Zhang K, Zhang X, Liu L, Wang J, Jin H, Liu Z, Zhang B, Li Y. Analysis of Hub Genes Involved in Distinction Between Aged and Fetal Bone Marrow Mesenchymal Stem Cells by Robust Rank Aggregation and Multiple Functional Annotation Methods. Front Genet 2020; 11:573877. [PMID: 33424919 PMCID: PMC7793715 DOI: 10.3389/fgene.2020.573877] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Accepted: 11/24/2020] [Indexed: 12/25/2022] Open
Abstract
Stem cells from fetal tissue protect against aging and possess greater proliferative capacity than their adult counterparts. These cells can more readily expand in vitro and senesce later in culture. However, the underlying molecular mechanisms for these differences are still not fully understood. In this study, we used a robust rank aggregation (RRA) method to discover robust differentially expressed genes (DEGs) between fetal bone marrow mesenchymal stem cells (fMSCs) and aged adult bone marrow mesenchymal stem cells (aMSCs). Multiple methods, including gene set enrichment analysis (GSEA), Gene Ontology (GO) analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed for functional annotation of the robust DEGs, and the results were visualized using the R software. The hub genes and other genes with which they interacted directly were detected by protein–protein interaction (PPI) network analysis. Correlation of gene expression was measured by Pearson correlation coefficient. A total of 388 up-regulated and 289 down-regulated DEGs were identified between aMSCs and fMSCs. We found that the down-regulated genes were mainly involved in the cell cycle, telomerase activity, and stem cell proliferation. The up-regulated DEGs were associated with cell adhesion molecules, extracellular matrix (ECM)–receptor interactions, and the immune response. We screened out four hub genes, MYC, KIF20A, HLA-DRA, and HLA-DPA1, through PPI-network analysis. The MYC gene was negatively correlated with TXNIP, an age-related gene, and KIF20A was extensively involved in the cell cycle. The results suggested that MSCs derived from the bone marrow of an elderly donor present a pro-inflammatory phenotype compared with that of fMSCs, and the HLA-DRA and HLA-DPA1 genes are related to the immune response. These findings provide new insights into the differences between aMSCs and fMSCs and may suggest novel strategies for ex vivo expansion and application of adult MSCs.
Collapse
Affiliation(s)
- Xiaoyao Liu
- Institute of Hard Tissue Development and Regeneration, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Mingjing Yin
- Institute of Hard Tissue Development and Regeneration, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Xinpeng Liu
- Institute of Hard Tissue Development and Regeneration, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Junlong Da
- Institute of Hard Tissue Development and Regeneration, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Kai Zhang
- Institute of Hard Tissue Development and Regeneration, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Xinjian Zhang
- Institute of Hard Tissue Development and Regeneration, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Lixue Liu
- Institute of Hard Tissue Development and Regeneration, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Jianqun Wang
- Institute of Hard Tissue Development and Regeneration, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Han Jin
- Institute of Hard Tissue Development and Regeneration, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Zhongshuang Liu
- Institute of Hard Tissue Development and Regeneration, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Bin Zhang
- Institute of Hard Tissue Development and Regeneration, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.,Heilongjiang Academy of Medical Sciences, Harbin, China
| | - Ying Li
- Institute of Hard Tissue Development and Regeneration, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| |
Collapse
|
|
29
|
Zhu Z, Jin Z, Zhang H, Zhang M, Sun D. Knockdown of Kif20a inhibits growth of tumors in soft tissue sarcoma in vitro and in vivo. J Cancer 2020; 11:5088-5098. [PMID: 32742456 PMCID: PMC7378921 DOI: 10.7150/jca.44777] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2020] [Accepted: 05/29/2020] [Indexed: 12/20/2022] Open
Abstract
Kif20a (Kinesin Family Member 20A), plays a role in cell mitosis, cell migration and intracellular transport. Numerous studies have demonstrated that Kif20a is abnormally highly expressed in a variety of tumors and shows poor prognosis. Soft tissue sarcoma (STS) represents a group of malignant tumors with poor prognosis. The role of Kif20a in STSs has not been systematically studied. In the present study, bioinformatics analysis, in vitro and in vivo experiments were conducted to investigate the function of Kif20a in STSs. In bioinformatics analysis higher KIf20a expression indicated a poor prognosis. Functional enrichment analysis indicated that Kif20a may be related to cell cycle, p53 and other signaling pathways. In vitro experiments showed that after the down-regulation of Kif20a, cell proliferation, migration and invasion were decreased, while apoptosis was increased. In vivo experiments revealed that Kif20a affected the proliferation of tumors in tumor-bearing mice. In summary, our findings revealed that Kif20a performs an important role in STS, indicating that it is a potential prognostic biomarker and potentially representing a therapeutic target for the disease.
Collapse
Affiliation(s)
- Zhenhua Zhu
- Department of Orthopaedic Trauma, The First Hospital of Jilin University, Xinmin Street 71#, Changchun City, Jilin Province, China
| | - Zheng Jin
- Department of Immunology, College of Basic Medical Sciences, Jilin University, Xinmin Street 126#, Changchun City, Jilin Province, China
| | - Haibo Zhang
- College of Chemistry, Jilin University, Changchun, Jilin Province, China
| | - Mei Zhang
- College of Chemistry, Jilin University, Changchun, Jilin Province, China
| | - Dahui Sun
- Department of Orthopaedic Trauma, The First Hospital of Jilin University, Xinmin Street 71#, Changchun City, Jilin Province, China
| |
Collapse
|
|
30
|
Wang X, Shu K, Wang Z, Ding D, Li X. Prognostic value of long non-coding RNA TP73-AS1 expression in different types of cancer: A systematic review and meta-analysis. ELECTRON J BIOTECHN 2020. [DOI: 10.1016/j.ejbt.2019.12.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022] Open
|
|
31
|
Xie F, He C, Gao S, Yang Z, Li L, Qiao L, Fang L. KIF20A silence inhibits the migration, invasion and proliferation of non-small cell lung cancer and regulates the JNK pathway. Clin Exp Pharmacol Physiol 2020; 47:135-142. [PMID: 31557334 DOI: 10.1111/1440-1681.13183] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2019] [Revised: 09/21/2019] [Accepted: 09/23/2019] [Indexed: 12/22/2022]
Abstract
An increasing number of studies have shown that kinesin family member 20A (KIF20A) was overexpressed in several types of cancer, and its overexpression correlated with the oncogenesis and prognosis of cancers. However, little is known about the roles of KIF20A in human non-small cell lung cancer (NSCLC). Thus, the aim of the present study was to demonstrate the expression of KIF20A in human NSCLC and reveal its biological functions and the underlying mechanisms. qRT-PCR, western blot and immunohistochemistry were used to assess the expression of NSCLC patient specimens and NSCLC cell lines. The functions of KIF20A in migration and invasion were determined using Transwell assay. Cell proliferation capacity was performed by CKK-8 assay. We demonstrated that KIF20A was overexpressed in NSCLC specimens compared with the adjacent non-tumorous specimens, and high expression of KIF20A was associated with clinical stage and metastasis in NSCLC. Decreased expression of KIF20A inhibited NSCLC cells migration, invasion and proliferation. Most importantly, further experiments demonstrated that decreased the expression of KLF20A significantly downregulated expression of p-JNK and MMP7, which indicated that knockdown of KIF20A alters lung cancer cell phenotype and regulates JNK pathways. These results suggest that KIF20A may act as a putative oncogene and a potential therapeutic target in NSCLC.
Collapse
Affiliation(s)
- Feng Xie
- China-Japan Union Hospital of Jilin Universtity, Chang chun, China
| | - Chengyan He
- China-Japan Union Hospital of Jilin Universtity, Chang chun, China
| | - Shen Gao
- China-Japan Union Hospital of Jilin Universtity, Chang chun, China
| | - Zhaowei Yang
- China-Japan Union Hospital of Jilin Universtity, Chang chun, China
| | - Lihong Li
- China-Japan Union Hospital of Jilin Universtity, Chang chun, China
| | - Lu Qiao
- China-Japan Union Hospital of Jilin Universtity, Chang chun, China
| | - Ling Fang
- China-Japan Union Hospital of Jilin Universtity, Chang chun, China
| |
Collapse
|
|
32
|
Li X, Shu K, Wang Z, Ding D. Prognostic significance of KIF2A and KIF20A expression in human cancer: A systematic review and meta-analysis. Medicine (Baltimore) 2019; 98:e18040. [PMID: 31725680 PMCID: PMC6867763 DOI: 10.1097/md.0000000000018040] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND The kinesin family (KIF) is reported to be aberrantly expressed and significantly correlated with survival outcomes in patients with various cancers. This meta-analysis was carried out to quantitatively evaluate the prognostic values of partial KIF members in cancer patients. METHODS Two well-known KIF members, KIF2A and KIF20A, were investigated to evaluate their potential values as novel prognostic biomarkers in human cancer. A comprehensive literature search was carried out of the PubMed, EMBASE, Cochrane Library, and Web of Science databases up to April 2019. Pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the association of KIF2A and KIF20A expression with overall survival (OS) and clinicopathological parameters. RESULTS Twenty-five studies involving 7262 patients were finally incorporated, including nine about KIF2A and sixteen about KIF20A. Our results indicated that patients with high expression of KIF2 and KIF20A tended to have shorter OS than those with low expression (HR = 2.23, 95% CI = 1.87-2.65, P < .001; HR = 1.77, 95% CI = 1.57-1.99, P < .001, respectively). Moreover, high expression of these 2 KIF members was significantly associated with advanced clinical stage (OR = 1.98, 95% CI: 1.57-2.50, P < .001; OR = 2.63, 95% CI: 2.03-3.41, P < .001, respectively), positive lymph node metastasis (OR = 2.32, 95% CI: 1.65-3.27, P < .001; OR = 2.13, 95% CI: 1.59-2.83, P < .001, respectively), and distant metastasis (OR = 2.20, 95% CI: 1.21-3.99, P = .010; OR = 5.25, 95% CI: 2.82-9.77, P < .001, respectively); only high KIF20A expression was related to poor differentiation grade (OR = 1.82, 95% CI: 1.09-3.07, P = .023). CONCLUSIONS High expression of KIF2 and KIF20A in human cancer was significantly correlated with worse prognosis and unfavorable clinicopathological features, suggesting that these 2 KIF members can be used as prognostic biomarkers for different types of tumors. PROSPERO REGISTRATION NUMBER CRD42019134928.
Collapse
Affiliation(s)
- Xing Li
- Department of Urology, People's Hospital of Zhengzhou University
| | - Kunpeng Shu
- Department of Urology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou, Henan, China
| | - Zhifeng Wang
- Department of Urology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou, Henan, China
| | - Degang Ding
- Department of Urology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou, Henan, China
| |
Collapse
|
|
33
|
Min C, Zhang A, Qin J. Increased expression of miR-601 is associated with poor prognosis and tumor progression of gastric cancer. Diagn Pathol 2019; 14:107. [PMID: 31547835 PMCID: PMC6757374 DOI: 10.1186/s13000-019-0882-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2019] [Accepted: 09/02/2019] [Indexed: 02/03/2023] Open
Abstract
Background MicroRNAs (miRNAs) have been considered to participate in many tumorigenesis, including gastric cancer (GC). Abnormal expression of miR-601 has been reported in GC, but its role is not clear. The goal of this study is to explore the expression patterns, clinical value and functional role of miR-601 in GC. Methods Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to evaluate the expression level of miR-601. The association between miR-601 expression and overall survival was estimated by the Kaplan-Meier survival method. The significance of different variables with respect to survival was analyzed by using the Cox regression assay. Cell experiments were applied to investigate the functional role of miR-601 in GC. Results We found that miR-601 was significantly up-regulated in GC tissues and cells compared with the controls (all P < 0.01). The levels of miR-601 expression were significantly associated with TNM stage, lymph node metastasis, lymphatic invasion, and distant metastasis (all P < 0.05). Kaplan-Meier survival analysis showed that patients in the high miR-601 expression group had poor overall survival (log-rank P = 0.001). Moreover, we confirmed that miR-601, TNM stage, and distant metastasis were independent prognostic factors for GC patients. Overexpression of miR-601 in AGS and SGC-7901 cells by miR-601 mimic transfection significantly promoted the cell proliferation, migration, and invasion (P < 0.05). Conclusions The expression level of miR-601 is dramatically up-regulated in GC. The overexpression of miR-601 promotes the tumor progression of GC, and may be a novel prognostic factor for poor survival in GC patients.
Collapse
Affiliation(s)
- Cuili Min
- Department of Laboratory Medicine, Yidu Central Hospital of Weifang, No.4138, South Linglongshan Road, Shandong, 262500, China.
| | - Aixia Zhang
- Department of Laboratory Medicine, Yidu Central Hospital of Weifang, No.4138, South Linglongshan Road, Shandong, 262500, China
| | - Jing Qin
- Department of Laboratory Medicine, Yidu Central Hospital of Weifang, No.4138, South Linglongshan Road, Shandong, 262500, China
| |
Collapse
|
|
34
|
Aberrant KIF20A Expression Is Associated with Adverse Clinical Outcome and Promotes Tumor Progression in Prostate Cancer. DISEASE MARKERS 2019; 2019:4782730. [PMID: 31565099 PMCID: PMC6745134 DOI: 10.1155/2019/4782730] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/18/2019] [Accepted: 07/30/2019] [Indexed: 12/24/2022]
Abstract
Purpose KIF20A is essential in the process of spindle assembly and cytokinesis regulation. The role of KIF20A during tumorigenesis and tumor development has been well studied in several cancers. But the association between the KIF20A clinical role and prostate cancer (PCa) has not been reported yet. In this study, we investigated its potential prognostic effect and its role in progression of prostate cancer. Methods Real-time quantitative polymerase chain reaction and Western blots were used to investigate the KIF20A transcription and translation levels in 7 pairs of fresh PCa tissue and adjacent normal prostate tissue. Immunohistochemistry (IHC) was used to investigate the KIF20A protein level in 114 PCa tissue samples. Bioinformatics analysis was performed to analyze the effect of KIF20A in oncologic prognosis in PCa patients. MTT assay, transwell assay, and colony formation assay in vitro and tumor formation assay in vivo were performed to evaluate the biological behavior of KIF20A in prostate cancer. Results KIF20A was significantly elevated in tumor tissue compared with normal prostate tissue at both the mRNA and the protein level. High expression of KIF20A at the protein level was correlated with adverse clinicopathological features. Bioinformatics analysis showed that the high KIF20A expression group has a poor biochemical recurrence- (BCR-) free survival. Knocking down KIF20A suppressed the proliferation, migration, and invasion of the prostate cancer cell both in vitro and in vivo. Conclusions Our data demonstrated that the high expression of KIF20A was associated with poor clinical outcome and targeting KIF20A could reduce proliferation, migration, and invasion of the prostate cancer cell, indicating that KIF20A might be a potential prognostic and therapeutic target for PCa patients.
Collapse
|
|
35
|
Tang J, Xu J, Zhi Z, Wang X, Wang Y, Zhou Y, Chen R. MiR-876-3p targets KIF20A to block JAK2/STAT3 pathway in glioma. Am J Transl Res 2019; 11:4957-4966. [PMID: 31497212 PMCID: PMC6731397] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2019] [Accepted: 06/25/2019] [Indexed: 06/10/2023]
Abstract
Aberrant expression of miRNAs has been reported to be involved in the development and progression of glioma. But the function of miR-876-3p in glioma is unknown. We found that miR-876-3p is significantly downregulated in glioma tissues and cell lines. Overexpression of miR-876-3p suppressed glioma cell proliferation, epithelial-mesenchymal transition, migration, and invasion. By prediction combining with luciferase reporter assay, we identified that miR-876-3p could decrease the expression of KIF20A by directly targeting the region of its 3'UTR. Furthermore, we observed that overexpression of miR-876-3p inhibited the expression of KIF20A, thus blocking the protein kinase JAK2/STAT3 pathway. Overexpressed KIF20A reversed miR-876-3p-induced suppression of glioma cell proliferation, migration, and invasion. We also demonstrated the inhibitory effect of miR-876-3p on tumor growth in glioma using an in vivo model. The miR-876-3p/KIF20A-axis mediated JAK2/STAT3 pathway have therapeutic potential in glioma treatment.
Collapse
Affiliation(s)
- Jiao Tang
- Department of Neurology, Yan Cheng City No. 1 People’s HospitalYancheng City, Jiangsu Province, China
| | - Jie Xu
- Department of General Surgery, Huai’an First People’s Hospital and The Affiliated Huai’an No. 1 People’s Hospital of Nanjing Medical UniversityHuai’an, Jiangsu Province, China
| | - Zhongwen Zhi
- Department of Neurology, The Second People’s Hospital of Huai’an and The Affiliated Huai’an Hospital of Xuzhou Medical UniversityHuai’an, Jiangsu Province, China
| | - Xiang Wang
- Department of Neurology, The Second People’s Hospital of Huai’an and The Affiliated Huai’an Hospital of Xuzhou Medical UniversityHuai’an, Jiangsu Province, China
| | - Yu Wang
- Department of Neurology, The Fourth Affiliated Hospital of Nanjing Medical University, Nanjing Pukou HospitalNanjing 210031, Jiangsu Province, China
| | - Yong Zhou
- Department of Neurology, The Second People’s Hospital of Huai’an and The Affiliated Huai’an Hospital of Xuzhou Medical UniversityHuai’an, Jiangsu Province, China
| | - Rui Chen
- Department of Neurology, The Second People’s Hospital of Huai’an and The Affiliated Huai’an Hospital of Xuzhou Medical UniversityHuai’an, Jiangsu Province, China
| |
Collapse
|
|
36
|
Identification of KIF11 As a Novel Target in Meningioma. Cancers (Basel) 2019; 11:cancers11040545. [PMID: 30991738 PMCID: PMC6521001 DOI: 10.3390/cancers11040545] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2019] [Revised: 04/09/2019] [Accepted: 04/11/2019] [Indexed: 12/11/2022] Open
Abstract
Kinesins play an important role in many physiological functions including intracellular vesicle transport and mitosis. The emerging role of kinesins in different cancers led us to investigate the expression and functional role of kinesins in meningioma. Therefore, we re-analyzed our previous microarray dataset of benign, atypical, and anaplastic meningiomas (n = 62) and got evidence for differential expression of five kinesins (KIFC1, KIF4A, KIF11, KIF14 and KIF20A). Further validation in an extended study sample (n = 208) revealed a significant upregulation of these genes in WHO°I to °III meningiomas (WHO°I n = 61, WHO°II n = 88, and WHO°III n = 59), which was most pronounced in clinically more aggressive tumors of the same WHO grade. Immunohistochemical staining confirmed a WHO grade-associated upregulated protein expression in meningioma tissues. Furthermore, high mRNA expression levels of KIFC1, KIF11, KIF14 and KIF20A were associated with shorter progression-free survival. On a functional level, knockdown of kinesins in Ben-Men-1 cells and in the newly established anaplastic meningioma cell line NCH93 resulted in a significantly inhibited tumor cell proliferation upon siRNA-mediated downregulation of KIF11 in both cell lines by up to 95% and 71%, respectively. Taken together, in this study we were able to identify the prognostic and functional role of several kinesin family members of which KIF11 exhibits the most promising properties as a novel prognostic marker and therapeutic target, which may offer new treatment options for aggressive meningiomas.
Collapse
|