AccScience Publishing / TD / Online First / DOI: 10.36922/td.2846
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ORIGINAL RESEARCH ARTICLE

Effect and mechanism of the PTMAP5–hsa-miR-22-3p–KIF2C regulatory axis on the occurrence and development of hepatocellular carcinoma

Qing Deng1 ,  Yuanchao Wei1 ,  Jiali Meng1 ,  Xiaolong Li2*
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1 Department of Clinical Medicine, Faculty of First Clinical Medical College, Guangxi Medical University, Nanning, Guangxi, China
2 Department of Cell Biology and Genetics, School of Preclinical Medicine, Key Laboratory of Longevity and Aging-related Diseases of Chinese Ministry of Education, Guangxi Medical University, Nanning, Guangxi, China
Tumor Discovery 2024, 3(3), 2846 https://doi.org/10.36922/td.2846
Submitted: 30 January 2024 | Accepted: 10 July 2024 | Published: 24 September 2024
© 2024 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Hepatocellular carcinoma (HCC), a primary liver cancer, is known for its high malignancy potential. Despite extensive research, the etiology of HCC remains elusive, with numerous molecular mechanisms yet to be deciphered. This study delves into the influence and mechanism of the PTMAP5–hsa-miR-22-3p–KIF2C regulatory axis in HCC pathogenesis. A comparative analysis of gene expression profiles between the GSE87630 and GSE45267 datasets unveiled a cohort of 346 differentially expressed genes. Protein–protein interaction networks were established using the STRING database, and key genes were identified through receiver operating characteristic curve analysis and LASSO regression analysis. The expression and prognostic value of these key genes were further evaluated using GEPIA and Kaplan–Meier analysis. Upstream miRNAs were predicted using the MiRTarBase and StarBase databases, facilitating the construction of the PTMAP5–hsa-miR-22-3p–KIF2C regulatory axis. Co-expression analysis of KIF2C was performed through UALCAN and StarBase, and the regulatory axis was found to play a pivotal role in HCC development through the cell cycle, oocyte meiosis, and FOXO signaling, as revealed by DAVID enrichment analysis. Furthermore, the expression and prognostic significance of KIF2C in various cancer types were assessed using TIMER and GEPIA, while TISIDB analysis revealed correlations between KIF2C expression and relevant major histocompatibility complex molecules, immunomodulators, chemokines, receptors, and immune variants in HCC. These findings also extended to HCC molecular subtypes. In conclusion, we constructed a novel PTMAP5–hsa-miR-22-3p–KIF2C regulatory subnetwork, which could provide valuable therapeutic targets and diagnostic markers for HCC.

Keywords
PTMAP5–hsa-miR-22-3p–KIF2C regulatory axis
Hepatocellular carcinoma
Bioinformatics
Receiver operating characteristic curve analysis
LASSO regression analysis
Funding
This research was funded by the Natural Science Foundation of Guangxi Province (grant number: 2017GXNSFAA198063) and the Basic Medical Science and Technology Innovation Training Fund Project of Guangxi Medical University (grant number: GXMUBMSTCF-G15).
Conflict of interest
The authors declare that they have no competing interests.
References
  1. World Health Organization. Cancer Today: Cancer Fact Sheets. Available from: https://gco.iarc.who.int/today/en/ fact-sheets-cancers [Last accessed on 2023 Dec 05].

 

  1. Kulik L, El-Serag HB. Epidemiology and management of hepatocellular carcinoma. Gastroenterology. 2019;156(2):477-491.e1. doi: 10.1053/j.gastro.2018.08.065

 

  1. EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol. 2018;69(1):182-236. doi: 10.1016/j.jhep.2018.03.019

 

  1. Barletta E, Tinessa V, Daniele B. Screening of hepatocellular carcinoma: Role of the alpha-fetoprotein (AFP) and ultrasonography. Recenti Prog Med. 2005;96(6):295-299.

 

  1. Prensner JR, Chinnaiyan AM. The emergence of lncRNAs in cancer biology. Cancer Discov. 2011;1(5):391-407. doi: 10.1158/2159-8290.CD-11-0209

 

  1. Mighell AJ, Smith NR, Robinson PA, Markham AF. Vertebrate pseudogenes. FEBS Lett. 2000;468(2-3):109-114. doi: 10.1016/s0014-5793(00)01199-6

 

  1. Ling H, Vincent K, Pichler M, et al. Junk DNA and the long non-coding RNA twist in cancer genetics. Oncogene. 2015;34(39):5003-5011. doi: 10.1038/onc.2014.456

 

  1. Nakamura-García AK, Espinal-Enríquez J. Pseudogenes in cancer: State of the art. Cancers (Basel). 2023;15(16):4024. doi: 10.3390/cancers15164024

 

  1. Meng J, Wei Y, Deng Q, Li L, Li X. Study on the expression of TOP2A in hepatocellular carcinoma and its relationship with patient prognosis. Cancer Cell Int. 2022;22(1):29. doi: 10.1186/s12935-021-02439-0

 

  1. Barrett T, Wilhite SE, Ledoux P, et al. NCBI GEO: Archive for functional genomics data sets--update. Nucleic Acids Res. 2013;41(Database issue):D991-D995. doi: 10.1093/nar/gks1193

 

  1. Huang HY, Lin YCD, Cui S, et al. miRTarBase update 2022: An informative resource for experimentally validated miRNA-target interactions. Nucleic Acids Res. 2022;50(D1):D222-D230. doi: 10.1093/nar/gkab1079

 

  1. Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z. GEPIA: A web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 2017;45(W1):W98-W102. doi: 10.1093/nar/gkx247

 

  1. Chandrashekar DS, Karthikeyan SK, Korla PK, et al. UALCAN: An update to the integrated cancer data analysis platform. Neoplasia. 2022;25:18-27. doi: 10.1016/j.neo.2022.01.001

 

  1. Sherman BT, Hao M, Qiu J, et al. DAVID: A web server for functional enrichment analysis and functional annotation of gene lists (2021 update). Nucleic Acids Res. 2022;50(W1):W216-W221. doi: 10.1093/nar/gkac194

 

  1. Li JH, Liu S, Zhou H, Qu LH, Yang JH. starBase v2.0: Decoding miRNA-ceRNA, miRNA-ncRNA and protein- RNA interaction networks from large-scale CLIP-Seq data. Nucleic Acids Res. 2014;42(Database issue):D92-D97. doi: 10.1093/nar/gkt1248

 

  1. Ru B, Wong CN, Tong Y, et al. TISIDB: An integrated repository portal for tumor-immune system interactions. Bioinformatics. 2019;35(20):4200-4202. doi: 10.1093/bioinformatics/btz210

 

  1. Zhou JW, Wang H, Sun W, Han NN, Chen L. ASPM is a predictor of overall survival and has therapeutic potential in endometrial cancer. Am J Transl Res. 2020;12(5):1942-1953.

 

  1. Li L, Kong XA, Zang M, et al. Hsa_circ_0003732 promotes osteosarcoma cells proliferation via miR-545/CCNA2 axis. Biosci Rep. 2020;40(6):BSR20191552. doi: 10.1042/BSR20191552

 

  1. Li J, Chen Y, Wang X, Wang C. CDCA2 triggers in vivo and in vitro proliferation of hepatocellular carcinoma by activating the AKT/CCND1 signaling. J BUON. 2021;26(3):882-888.

 

  1. Liao W, Liu W, Liu X, et al. Upregulation of FAM83D affects the proliferation and invasion of hepatocellular carcinoma. Oncotarget. 2015;6(27):24132-24147. doi: 10.18632/oncotarget.4432

 

  1. Chen J, Li S, Zhou S, et al. Kinesin superfamily protein expression and its association with progression and prognosis in hepatocellular carcinoma. J Cancer Res Ther. 2017;13(4):651-659. doi: 10.4103/jcrt.JCRT_491_17

 

  1. Huang P, Gu Y, Guo L, Zou X, Yi L, Wu G. Bioinformatics analysis and screening of potential target genes related to the lung cancer prognosis. Med Princ Pract. 2023. doi: 10.1159/000533891

 

  1. Guo J, Zhang W, Sun L, et al. KIF2C accelerates the development of non-small cell lung cancer and is suppressed by miR-186-3p via the AKT-GSK3β-β-catenin pathway. Sci Rep. 2023;13(1):7288. doi: 10.1038/s41598-023-30073-5

 

  1. Huang X, Zhao F, Wu Q, et al. KIF2C facilitates tumor growth and metastasis in pancreatic ductal adenocarcinoma. Cancers (Basel). 2023;15(5):1502. doi: 10.3390/cancers15051502

 

  1. Li X, Huang W, Huang W, et al. Kinesin family members KIF2C/4A/10/11/14/18B/20A/23 predict poor prognosis and promote cell proliferation in hepatocellular carcinoma. Am J Transl Res. 2020;12(5):1614-1639.

 

  1. Shen T, Yang L, Zhang Z, et al. KIF20A affects the prognosis of bladder cancer by promoting the proliferation and metastasis of bladder cancer cells. Dis Markers. 2019;2019:4863182. doi: 10.1155/2019/4863182

 

  1. Keyhanian K, Lage JM, Chernetsova E, Sekhon H, Eslami Z, Islam S. Combination of MCM2 with Ki67 and p16 immunohistochemistry can distinguish uterine leiomyosarcomas. Int J Gynecol Pathol. 2020;39(4):354-361. doi: 10.1097/PGP.0000000000000616

 

  1. Liu Z, Li J, Chen J, et al. MCM family in HCC: MCM6 indicates adverse tumor features and poor outcomes and promotes S/G2 cell cycle progression. BMC Cancer. 2018;18(1):200. doi: 10.1186/s12885-018-4056-8

 

  1. Blackledge NP, Fursova NA, Kelley JR, Huseyin MK, Feldmann A, Klose RJ. PRC1 catalytic activity is central to polycomb system function. Mol Cell. 2020;77(4):857-874.e9. doi: 10.1016/j.molcel.2019.12.001

 

  1. Del Re M, Bertolini I, Crucitta S, et al. Overexpression of TK1 and CDK9 in plasma-derived exosomes is associated with clinical resistance to CDK4/6 inhibitors in metastatic breast cancer patients. Breast Cancer Res Treat. 2019;178(1):57-62. doi: 10.1007/s10549-019-05365-y

 

  1. Zhou F, Wang M, Aibaidula M, et al. TPX2 promotes metastasis and serves as a marker of poor prognosis in non-small cell lung cancer. Med Sci Monit. 2020;26:e925147. doi: 10.12659/MSM.925147

 

  1. Li K, Zhang R, Wei M, et al. TROAP promotes breast cancer proliferation and metastasis. Biomed Res Int. 2019;2019:6140951. doi: 10.1155/2019/6140951

 

  1. Wang-Bishop L, Chen Z, Gomaa A, et al. Inhibition of AURKA reduces proliferation and survival of gastrointestinal cancer cells with activated KRAS by preventing activation of RPS6KB1. Gastroenterology. 2019;156(3):662-675.e7. doi: 10.1053/j.gastro.2018.10.030

 

  1. Wang L, Zhang J, Wan L, Zhou X, Wang Z, Wei W. Targeting Cdc20 as a novel cancer therapeutic strategy. Pharmacol Ther. 2015;151:141-151. doi: 10.1016/j.pharmthera.2015.04.002

 

  1. Sun J, Huang J, Lan J, et al. Overexpression of CENPF correlates with poor prognosis and tumor bone metastasis in breast cancer. Cancer Cell Int. 2019;19:264. doi: 10.1186/s12935-019-0986-8

 

  1. Kang DH, Woo J, Kim H, et al. Prognostic relevance of HJURP expression in patients with surgically resected colorectal cancer. Int J Mol Sci. 2020;21(21):7928. doi: 10.3390/ijms21217928

 

  1. Sun X, Chen P, Chen X, et al. KIF4A enhanced cell proliferation and migration via Hippo signaling and predicted a poor prognosis in esophageal squamous cell carcinoma. Thorac Cancer. 2021;12(4):512-524. doi: 10.1111/1759-7714.13787

 

  1. Wang D, Li Q, Li Y, Wang H. The role of MCM5 expression in cervical cancer: Correlation with progression and prognosis. Biomed Pharmacother. 2018;98:165-172. doi: 10.1016/j.biopha.2017.12.006

 

  1. Gong C, Ai J, Fan Y, et al. NCAPG promotes the proliferation of hepatocellular carcinoma through PI3K/AKT signaling. Onco Targets Ther. 2019;12:8537-8552. doi: 10.2147/OTT.S217916

 

  1. Meng C, Zou Y, Hong W, Bao C, Jia X. Estrogen-regulated PTTG1 promotes breast cancer progression by regulating cyclin kinase expression. Mol Med. 2020;26(1):33. doi: 10.1186/s10020-020-00161-7

 

  1. Liu T, Zhang H, Yi S, Gu L, Zhou M. Mutual regulation of MDM4 and TOP2A in cancer cell proliferation. Mol Oncol. 2019;13(5):1047-1058. doi: 10.1002/1878-0261.12457

 

  1. Agarwal S, Behring M, Kim HG, et al. TRIP13 promotes metastasis of colorectal cancer regardless of p53 and microsatellite instability status. Mol Oncol. 2020;14(12): 3007-3029. doi: 10.1002/1878-0261.12821

 

  1. Yin H, Wang X, Zhang X, et al. UBE2T promotes radiation resistance in non-small cell lung cancer via inducing epithelial-mesenchymal transition and the ubiquitination-mediated FOXO1 degradation. Cancer Lett. 2020;494: 121-131. doi: 10.1016/j.canlet.2020.06.005

 

  1. Lou W, Liu J, Gao Y, et al. MicroRNA regulation of liver cancer stem cells. Am J Cancer Res. 2018;8(7):1126-1141.

 

  1. Lou W, Liu J, Gao Y, et al. MicroRNAs in cancer metastasis and angiogenesis. Oncotarget. 2017;8(70):115787-115802. doi: 10.18632/oncotarget.23115

 

  1. Cai G, Wu D, Wang Z, et al. Collapsin response mediator protein-1 (CRMP1) acts as an invasion and metastasis suppressor of prostate cancer via its suppression of epithelial-mesenchymal transition and remodeling of actin cytoskeleton organization. Oncogene. 2017;36(4):546-558. doi: 10.1038/onc.2016.227

 

  1. Kazazian K, Go C, Wu H, et al. Plk4 promotes cancer invasion and metastasis through Arp2/3 complex regulation of the actin cytoskeleton. Cancer Res. 2017;77(2):434-447. doi: 10.1158/0008-5472.CAN-16-2060

 

  1. Chen YG, Satpathy AT, Chang HY. Gene regulation in the immune system by long noncoding RNAs. Nat Immunol. 2017;18(9):962-972. doi: 10.1038/ni.3771

 

  1. Ghafouri-Fard S, Taheri M. Long non-coding RNA signature in gastric cancer. Exp Mol Pathol. 2020;113:104365. doi: 10.1016/j.yexmp.2019.104365

 

  1. Hu PA, Miao YY, Yu S, Guo N. Long non-coding RNA SNHG5 promotes human hepatocellular carcinoma progression by regulating miR-363-3p/RNF38 axis. Eur Rev Med Pharmacol Sci. 2020;24(7):3592-3604. doi: 10.26355/eurrev_202004_20821

 

  1. Locy H, de Mey S, de Mey W, De Ridder M, Thielemans K, Maenhout SK. Immunomodulation of the tumor microenvironment: Turn foe into friend. Front Immunol. 2018;9:2909. doi: 10.3389/fimmu.2018.02909

 

  1. Mooradian MJ, Sullivan RJ. Immunomodulatory effects of current cancer treatment and the consequences for follow-up immunotherapeutics. Future Oncol. 2017;13(18):1649-1663. doi: 10.2217/fon-2017-0117

 

  1. Petitprez F, Meylan M, de Reyniès A, Sautès-Fridman C, Fridman WH. The tumor microenvironment in the response to immune checkpoint blockade therapies. Front Immunol. 2020;11:784. doi: 10.3389/fimmu.2020.00784
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Tumor Discovery, Electronic ISSN: 2810-9775 Print ISSN: 3060-8597, Published by AccScience Publishing
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