KNTC1 functions as a potential biomarker and oncogene regulating proliferation, migration and apoptosis in gastric cancer

被引:2
作者
Qi, Haoran [1 ]
Cao, Mengyuan [1 ]
Chen, Yanan [1 ]
Li, Xiaoya [1 ]
Wang, Yingfei [1 ]
Dai, Xiaoshuo [1 ]
Duan, Xiaoxuan [1 ]
Lu, Jing [1 ,2 ,3 ]
机构
[1] Zhengzhou Univ, Sch Basic Med Sci, Dept Pathophysiol, 100 Sci Ave, Zhengzhou 450001, Henan, Peoples R China
[2] Zhengzhou Univ, Collaborat Innovat Ctr Henan Prov Canc Chemopreven, Zhengzhou 450001, Henan, Peoples R China
[3] Zhengzhou Univ, State Key Lab Esophageal Canc Prevent & Treatment, Zhengzhou 450052, Henan, Peoples R China
关键词
KNTC1; Prognostic marker; Immune infiltration; Apoptosis; Gastric cancer; BIOINFORMATICS ANALYSIS; TUMOR MICROENVIRONMENT; KEY GENES; IDENTIFICATION; PATHWAY; EXPRESSION; GENOMICS; INVASION; CELLS; TOOL;
D O I
10.1016/j.intimp.2024.113257
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background As one of the most prevalent cancers, gastric cancer (GC) exhibits a remarkably high morbidity and mortality rate. To date, effective diagnostic and prognostic markers and therapeutic targets for GC are still lacking. Kinetochore associated 1 (KNTC1) is one of the proteins involved in chromosome segregation. However, the diagnostic and prognostic value of KNTC1 and its biological function in GC remain unknown. Methods In this study, Gene Expression Omnibus (GEO) datasets were utilized to identify differentially expressed genes (DEGs). Prognostic and diagnostic value were assessed by Kaplan-Meier plotter and receiver operating characteristic (ROC) curve. The expression of KNTC1 was verified by q-PCR, immunohistochemistry (IHC) and Western blotting. Subsequently, KNTC1 knockdown was employed to investigate its effect on GC cells. Gene set enrichment analysis (GSEA) revealed a pathway regulated by KNTC1, which was further verified by Western blotting. Results Four highly expressed genes (ESPL1, RAD54L, KNTC1, TACC3) were identified as biomarkers for GC diagnosis and prognosis. Notably, the value of KNTC1 as a biomarker for GC was newly revealed. Single-cell and immune analyses revealed that KNTC1 contributed to the suppression of the GC immune microenvironment. In clinical samples, we demonstrated high expression of KNTC1 in GC tissues. KNTC1 knockdown suppressed proliferation and migration while promoting apoptosis of GC cells. Additionally, KNTC1 may affect GC cells by regulating the PI3K/Akt/mTOR pathway. Conclusions KNTC1 acts as a potential diagnostic and prognostic marker for GC. It may promote proliferation and migration while inhibiting apoptosis of GC cells via the PI3K/Akt/mTOR pathway.
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页数:15
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共 69 条
[61]   Integrated bioinformatics analysis for differentially expressed genes and signaling pathways identification in gastric cancer [J].
Yang, ChenChen ;
Gong, Aifeng .
INTERNATIONAL JOURNAL OF MEDICAL SCIENCES, 2021, 18 (03) :792-800
[62]   KNTC1 knockdown inhibits proliferation and metastases of liver cancer [J].
Yang, Fan ;
Yuan, Changjin .
3 BIOTECH, 2023, 13 (09)
[63]   Identification of novel biomarkers, MUC5AC, MUC1, KRT7, GAPDH, CD44 for gastric cancer [J].
Yang, Jie .
MEDICAL ONCOLOGY, 2020, 37 (05)
[64]   Genomics of Drug Sensitivity in Cancer (GDSC): a resource for therapeutic biomarker discovery in cancer cells [J].
Yang, Wanjuan ;
Soares, Jorge ;
Greninger, Patricia ;
Edelman, Elena J. ;
Lightfoot, Howard ;
Forbes, Simon ;
Bindal, Nidhi ;
Beare, Dave ;
Smith, James A. ;
Thompson, I. Richard ;
Ramaswamy, Sridhar ;
Futreal, P. Andrew ;
Haber, Daniel A. ;
Stratton, Michael R. ;
Benes, Cyril ;
McDermott, Ultan ;
Garnett, Mathew J. .
NUCLEIC ACIDS RESEARCH, 2013, 41 (D1) :D955-D961
[65]   Inferring tumour purity and stromal and immune cell admixture from expression data [J].
Yoshihara, Kosuke ;
Shahmoradgoli, Maria ;
Martinez, Emmanuel ;
Vegesna, Rahulsimham ;
Kim, Hoon ;
Torres-Garcia, Wandaliz ;
Trevino, Victor ;
Shen, Hui ;
Laird, Peter W. ;
Levine, Douglas A. ;
Carter, Scott L. ;
Getz, Gad ;
Stemke-Hale, Katherine ;
Mills, Gordon B. ;
Verhaak, Roel G. W. .
NATURE COMMUNICATIONS, 2013, 4
[66]   Gut microbiota modulate CD8+ T cell immunity in gastric cancer through Butyrate/GPR109A/HOPX [J].
Yu, Xiang ;
Ou, Jinzhou ;
Wang, Lingzhi ;
Li, Zhenyuan ;
Ren, Yingxin ;
Xie, Lang ;
Chen, Zhian ;
Liang, Junxian ;
Shen, Guodong ;
Zou, Zhaowei ;
Zhao, Cuiyin ;
Li, Guoxin ;
Hu, Yanfeng .
GUT MICROBES, 2024, 16 (01)
[67]   KNTC1 knockdown suppresses cell proliferation of colon cancer [J].
Zhang Zhengxiang ;
Tao Yunxiang ;
Liu Zhiping ;
Yang Zhimin .
3 BIOTECH, 2021, 11 (06)
[68]   MAGOH/MAGOHB Inhibits the Tumorigenesis of Gastric Cancer via Inactivation of b-RAF/MEK/ERK Signaling [J].
Zhou, Yong ;
Li, Zhongqi ;
Wu, Xuan ;
Tou, Laizhen ;
Zheng, Jingjing ;
Zhou, Donghui .
ONCOTARGETS AND THERAPY, 2020, 13 :12723-12735
[69]   Computational Study on the Effect of Inactivating/Activating Mutations on the Inhibition of MEK1 by Trametinib [J].
Zhu, Jingxuan ;
Li, Congcong ;
Yang, Hengzheng ;
Guo, Xiaoqing ;
Huang, Tianci ;
Han, Weiwei .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2020, 21 (06)