Abstract
Background
There is growing evidence showing that 6-phosphofructo-2-kinase (PFKFB3) plays crucial roles in different types of human cancers, including LUAD; however, the specific mechanism by which PFKFB3 plays a role in LUAD remains unclear.
Methods
We investigated the expression of PFKFB3 and explored the underlying mechanism as well as the correlation with immune markers using several online datasets, such as Tumor Immune Estimate Resource (TIMER), UALCAN, and the Cancer Genome Atlas (TCGA) databases, miRWalk, Targetscan, MiRDB and starBase database. Western blot and immunohistochemistry analysis were performed to verify the corresponding outcomes.
Results
It was shown that the mRNA expression of PFKFB3 was lower in LUAD than in the normal tissues, while its protein expression was not consistent with the mRNA level. The expression of PFKFB3 was correlated with clinicopathological parameters and several signaling pathways. The potential long chain (lnc)RNA/microRNA/PFKFB3 axis and the possible mechanism by which tumor progression in LUAD is promoted was predicted. We obtained the LINC01798/LINC02086/AP000845.1/HAGLR-miR-17-5p-PFKFB3 axis after comprehensive analyses of expression, correlation, and survival. Moreover, the expression of PFKFB3 was positively correlated with immune cells and immune checkpoint expression, including PD-1, PD-L1 and CTLA-4.
Conclusion
The present study demonstrated that noncoding RNAs mediated the upregulation of PFKFB3 and was associated with a poor prognosis and immune tumor infiltration in LUAD.
Data Sharing Statement
The databases presented in this study were obtained from online repositories. All the data could be retrieved from following databases: TCGA (https://portal.gdc.cancer.gov/), TIMER (https://cistrome.shinyapps.io/timer/), UALCAN (http://ualcan.path.uab.edu/), GEPIA (http://gepia.cancer-pku.cn/), LinkedOmics (http://www.linkedomics.org/), miRWalk (http://mirwalk.umm.uni-heidelberg.de/), Targetscan (http://www.targetscan.org/), MiRDB (http://www.mirdb.org/) and Starbase (https://starbase.sysu.edu.cn/).
Ethics Approval and Consent to Participate
All patients consented to the use of their biological material for research in written form. The Ethics Committee of Affiliated Hospital of Nantong University approved our study.
Acknowledgments
We thank Taoming Mo for his contributions to the revision of the manuscript.
Author Contributions
All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approve of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.
Disclosure
The authors declare that there are no competing interests.