Identification and Experimental Validation of Prognostic miRNA Signature and Ferroptosis-Related Key Genes in Cervical Squamous Cell Carcinoma

被引:2
作者
Guo, Yan [1 ]
Han, Yana [1 ]
Zhang, Junjie [2 ]
Zhou, Yanbin [3 ]
Wei, Meiyan [1 ]
Yu, Lijun [1 ]
机构
[1] Shanxi Med Univ, Hosp 1, Dept Gynecol, Taiyuan, Peoples R China
[2] Shanxi Med Univ, Hosp 2, Dept Neurosurg, Taiyuan, Peoples R China
[3] Shanxi Med Univ, Hosp 1, Dept Teaching Affairs Sect, Taiyuan, Peoples R China
关键词
cervical squamous cell carcinoma; ferroptosis-related genes; miRNA signatures; prognostic biomarkers; BREAST-CANCER; EXPRESSION; MICRORNAS;
D O I
10.1002/cam4.70415
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
ObjectivesThis study aimed to investigate the prognostic value of miRNAs and ferroptosis-related genes in cervical squamous cell carcinoma.MethodsWe mined data from public databases for differentially expressed miRNAs, ferroptosis-related genes, and clinical parameters and constructed a prognostic risk model. The predictive performance of the model was evaluated using survival and receiver operating characteristic curve analyses. We combined the clinicopathological features to construct a nomogram and evaluated its efficacy using calibration and clinical decision curves. The correlation between miRNA characteristics, risk score, and the tumor microenvironment was also studied. Next, consensus and key genes were screened, and their biological functions were analyzed using KEGG, GO, GSEA, and drug sensitivity analysis. Finally, the expression of miRNAs and key genes was detected using qRT-PCR and western blotting to verify the prediction results.ResultsSeven miRNA signatures (miR-100-3p, miR-301a-5p, miR-331-3p, miR-425-5p, miR-502-3p, miR-505-5p, and miR-629-3p) were generated, and prognostic risk and nomogram models were successfully constructed. These models exhibited good accuracy. miRNA signatures correlated with the tumor microenvironment. Twelve consensus genes and three key genes (SLC2A1, ANO6, and TXNIP) were screened and their biofunctional diversity was identified using various analytical methods. qRT-PCR and western blotting were used to verify the expression of miR-301a-5p, miR-505-5p, SLC2A1, and TXNIP in cervical squamous carcinoma. The results were consistent with those of bioinformatics analyses.ConclusionsSeven miRNAs may serve as prognostic biomarkers of cervical squamous cell carcinoma. SLC2A1, ANO6, and TXNIP are associated with cervical squamous cell carcinoma and may serve as ferroptosis-related markers of the disease.
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页数:15
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共 45 条
[1]   Predicting effective microRNA target sites in mammalian mRNAs [J].
Agarwal, Vikram ;
Bell, George W. ;
Nam, Jin-Wu ;
Bartel, David P. .
ELIFE, 2015, 4
[2]   Regulatory Mechanism of MicroRNA Expression in Cancer [J].
Ali Syeda, Zainab ;
Langden, Siu Semar Saratu' ;
Munkhzul, Choijamts ;
Lee, Mihye ;
Song, Su Jung .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2020, 21 (05)
[3]   Glucose transporters in cancer - from tumor cells to the tumor microenvironment [J].
Ancey, Pierre-Benoit ;
Contat, Caroline ;
Meylan, Etienne .
FEBS JOURNAL, 2018, 285 (16) :2926-2943
[4]   Gene Ontology: tool for the unification of biology [J].
Ashburner, M ;
Ball, CA ;
Blake, JA ;
Botstein, D ;
Butler, H ;
Cherry, JM ;
Davis, AP ;
Dolinski, K ;
Dwight, SS ;
Eppig, JT ;
Harris, MA ;
Hill, DP ;
Issel-Tarver, L ;
Kasarskis, A ;
Lewis, S ;
Matese, JC ;
Richardson, JE ;
Ringwald, M ;
Rubin, GM ;
Sherlock, G .
NATURE GENETICS, 2000, 25 (01) :25-29
[5]   Facilitative glucose transporters: Implications for cancer detection, prognosis and treatment [J].
Barron, Carly C. ;
Bilan, Philip J. ;
Tsakiridis, Theodoros ;
Tsiani, Evangelia .
METABOLISM-CLINICAL AND EXPERIMENTAL, 2016, 65 (02) :124-139
[6]   MicroRNAs: Target Recognition and Regulatory Functions [J].
Bartel, David P. .
CELL, 2009, 136 (02) :215-233
[7]   Ferroptosis in Cancer Cell Biology [J].
Bebber, Christina M. ;
Mueller, Fabienne ;
Clemente, Laura Prieto ;
Weber, Josephine ;
von Karstedt, Silvia .
CANCERS, 2020, 12 (01)
[8]   GLUT1 biological function and inhibition: research advances [J].
Cao, Shuang ;
Chen, Yongshou ;
Ren, Yixin ;
Feng, Yingqi ;
Long, Sihui .
FUTURE MEDICINAL CHEMISTRY, 2021, 13 (14) :1227-1243
[9]   The cBio Cancer Genomics Portal: An Open Platform for Exploring Multidimensional Cancer Genomics Data [J].
Cerami, Ethan ;
Gao, Jianjiong ;
Dogrusoz, Ugur ;
Gross, Benjamin E. ;
Sumer, Selcuk Onur ;
Aksoy, Buelent Arman ;
Jacobsen, Anders ;
Byrne, Caitlin J. ;
Heuer, Michael L. ;
Larsson, Erik ;
Antipin, Yevgeniy ;
Reva, Boris ;
Goldberg, Arthur P. ;
Sander, Chris ;
Schultz, Nikolaus .
CANCER DISCOVERY, 2012, 2 (05) :401-404
[10]   miRNA Targeting: Growing beyond the Seed [J].
Chipman, Laura B. ;
Pasquinelli, Amy E. .
TRENDS IN GENETICS, 2019, 35 (03) :215-222