Noncoding RNAs-mediated Overexpression of KIF14 is Associated with Tumor Immune Infiltration and Unfavorable Prognosis in Lung Adenocarcinoma

Overview

Journal Aging (Albany NY)

Specialty Geriatrics

Date 2022 Oct 13

PMID 36227151

Authors

Hong Wang

Fangting Tang

Ping Tang

Liang Zhang

Qixin Gan

Yuejun Li

Affiliations

Soon will be listed here.

Abstract

Kinesin family member 14 (KIF14) is potentially oncogenic and acts as a chromokinesin via binding to microtubules and chromatin during the bipolar spindle formation. KIF14 overexpression is a significant prognostic biomarker in various cancers. However, the expression, prognosis, mechanism, and tumor immune regulation of KIF14 in lung adenocarcinoma (LUAD) remain obscure. Our results demonstrated that KIF14 was upregulated in a variety of cancers, including LUAD. High-expression of KIF14 in LUAD was associated with pathological tumor stage, N stage and unfavorable prognosis. Both univariate and multivariate Cox regression results demonstrated that KIF14 was a significant independent risk factor influencing the prognosis of LUAD patients. The most promising upstream ncRNA-associated pathway of KIF14 in LUAD was determined to be GSEC/TYMSOS-hsa-miR-101-3p axis according to the starBase and The Cancer Genome Atlas databases. Furthermore, upregulation of KIF14 in LUAD was positively correlated with tumor mutation burden, microsatellite instability, immune checkpoint-related gene expression, immune cell biomarkers, and tumor immune cell infiltration. This study reveals that ncRNAs-mediated overexpression of KIF14 is associated with tumor immune infiltration and unfavorable prognosis in LUAD.

Citing Articles

Targeting Kinesins for Therapeutic Exploitation of Chromosomal Instability in Lung Cancer.

Zhang C, Wu B, Thu K Cancers (Basel). 2025; 17(4).

PMID: 40002279 PMC: 11853690. DOI: 10.3390/cancers17040685.

IGF2BP1 promotes multiple myeloma with chromosome 1q gain via increasing CDC5L expression in an mA-dependent manner.

Xu J, Wang Y, Ren L, Li P, Liu P Genes Dis. 2024; 12(1):101214.

PMID: 39534570 PMC: 11554607. DOI: 10.1016/j.gendis.2024.101214.

Development of a cell adhesion-based prognostic model for multiple myeloma: Insights into chemotherapy response and potential reversal of adhesion effects.

Hu Q, Wang M, Wang J, Tao Y, Niu T Oncol Res. 2024; 32(4):753-768.

PMID: 38560563 PMC: 10972724. DOI: 10.32604/or.2023.043647.

Exploring diverse programmed cell-death patterns to develop a novel gene signature for predicting the prognosis of lung adenocarcinoma patients.

Ma Z, Wang Y, Yu Y, Fu F, Zhang Y J Thorac Dis. 2024; 16(2):911-923.

PMID: 38505063 PMC: 10944735. DOI: 10.21037/jtd-23-1275.

MiR-101: An Important Regulator of Gene Expression and Tumor Ecosystem.

Liu N, Yang C, Gao A, Sun M, Lv D Cancers (Basel). 2022; 14(23).

PMID: 36497343 PMC: 9739992. DOI: 10.3390/cancers14235861.

References

Xu H, Choe C, Shin S, Park S, Kim H, Jung S . Silencing of KIF14 interferes with cell cycle progression and cytokinesis by blocking the p27(Kip1) ubiquitination pathway in hepatocellular carcinoma. Exp Mol Med. 2014; 46:e97. PMC: 4044675. DOI: 10.1038/emm.2014.23. View

Theriault B, Pajovic S, Bernardini M, Shaw P, Gallie B . Kinesin family member 14: an independent prognostic marker and potential therapeutic target for ovarian cancer. Int J Cancer. 2011; 130(8):1844-54. DOI: 10.1002/ijc.26189. View

Siegel R, Miller K, Jemal A . Cancer statistics, 2020. CA Cancer J Clin. 2020; 70(1):7-30. DOI: 10.3322/caac.21590. View

Kornepati A, Vadlamudi R, Curiel T . Programmed death ligand 1 signals in cancer cells. Nat Rev Cancer. 2022; 22(3):174-189. PMC: 9989967. DOI: 10.1038/s41568-021-00431-4. View

Lou W, Wang W, Chen J, Wang S, Huang Y . ncRNAs-mediated high expression of SEMA3F correlates with poor prognosis and tumor immune infiltration of hepatocellular carcinoma. Mol Ther Nucleic Acids. 2021; 24:845-855. PMC: 8121632. DOI: 10.1016/j.omtn.2021.03.014. View

Xu Q, Chen Y . An Aging-Related Gene Signature-Based Model for Risk Stratification and Prognosis Prediction in Lung Adenocarcinoma. Front Cell Dev Biol. 2021; 9:685379. PMC: 8283194. DOI: 10.3389/fcell.2021.685379. View

Klimaszewska-Wisniewska A, Neska-Dlugosz I, Buchholz K, Durslewicz J, Grzanka D, Kasperska A . Prognostic Significance of KIF11 and KIF14 Expression in Pancreatic Adenocarcinoma. Cancers (Basel). 2021; 13(12). PMC: 8234517. DOI: 10.3390/cancers13123017. View

Benoit M, Asenjo A, Paydar M, Dhakal S, Kwok B, Sosa H . Structural basis of mechano-chemical coupling by the mitotic kinesin KIF14. Nat Commun. 2021; 12(1):3637. PMC: 8206134. DOI: 10.1038/s41467-021-23581-3. View

Sezer A, Kilickap S, Gumus M, Bondarenko I, Ozguroglu M, Gogishvili M . Cemiplimab monotherapy for first-line treatment of advanced non-small-cell lung cancer with PD-L1 of at least 50%: a multicentre, open-label, global, phase 3, randomised, controlled trial. Lancet. 2021; 397(10274):592-604. DOI: 10.1016/S0140-6736(21)00228-2. View

10.

Powles T, van der Heijden M, Castellano D, Galsky M, Loriot Y, Petrylak D . Durvalumab alone and durvalumab plus tremelimumab versus chemotherapy in previously untreated patients with unresectable, locally advanced or metastatic urothelial carcinoma (DANUBE): a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol. 2020; 21(12):1574-1588. DOI: 10.1016/S1470-2045(20)30541-6. View

11.

Chew Y, Cross R . Molecular Motors: Kif14's Disordered Dongle. Curr Biol. 2020; 30(17):R988-R991. DOI: 10.1016/j.cub.2020.06.095. View

12.

Liu J, Li D, Zhang X, Li Y, Ou J . Histone Demethylase Promotes Cervical Cancer Malignancy Through the /KIF14/Hedgehog Axis. Onco Targets Ther. 2020; 13:11957-11973. PMC: 7682655. DOI: 10.2147/OTT.S276559. View

13.

Liu M, Li J, Huang Z, Li Y . Gastric cancer risk-scoring system based on analysis of a competing endogenous RNA network. Transl Cancer Res. 2022; 9(6):3889-3902. PMC: 8798172. DOI: 10.21037/tcr-19-2977. View

14.

Wu Q, Luo X, Terp M, Li Q, Li Y, Shen L . DDX56 modulates post-transcriptional Wnt signaling through miRNAs and is associated with early recurrence in squamous cell lung carcinoma. Mol Cancer. 2021; 20(1):108. PMC: 8393456. DOI: 10.1186/s12943-021-01403-w. View

15.

Grant M, Herbst R, Goldberg S . Selecting the optimal immunotherapy regimen in driver-negative metastatic NSCLC. Nat Rev Clin Oncol. 2021; 18(10):625-644. DOI: 10.1038/s41571-021-00520-1. View

16.

Li T, Fan J, Wang B, Traugh N, Chen Q, Liu J . TIMER: A Web Server for Comprehensive Analysis of Tumor-Infiltrating Immune Cells. Cancer Res. 2017; 77(21):e108-e110. PMC: 6042652. DOI: 10.1158/0008-5472.CAN-17-0307. View

17.

Basavarajappa H, Corson T . KIF14 as an oncogene in retinoblastoma: a target for novel therapeutics?. Future Med Chem. 2012; 4(17):2149-52. DOI: 10.4155/fmc.12.158. View

18.

Wang Q, Wang L, Li D, Deng J, Zhao Z, He S . Kinesin family member 14 is a candidate prognostic marker for outcome of glioma patients. Cancer Epidemiol. 2012; 37(1):79-84. DOI: 10.1016/j.canep.2012.08.011. View

19.

Corson T, Zhu C, Lau S, Shepherd F, Tsao M, Gallie B . KIF14 messenger RNA expression is independently prognostic for outcome in lung cancer. Clin Cancer Res. 2007; 13(11):3229-34. DOI: 10.1158/1078-0432.CCR-07-0393. View

20.

Mizuno H, Kitada K, Nakai K, Sarai A . PrognoScan: a new database for meta-analysis of the prognostic value of genes. BMC Med Genomics. 2009; 2:18. PMC: 2689870. DOI: 10.1186/1755-8794-2-18. View