KIF11 Serves as an Independent Prognostic Factor and Therapeutic Target for Patients With Lung Adenocarcinoma

Zhaodong Li; Bingxin Yu; Fangyuan Qi; Fan Li

doi:10.3389/fonc.2021.670218

KIF11 Serves as an Independent Prognostic Factor and Therapeutic Target for Patients With Lung Adenocarcinoma

Front Oncol. 2021 Apr 23:11:670218. doi: 10.3389/fonc.2021.670218. eCollection 2021.

Authors

Zhaodong Li¹, Bingxin Yu², Fangyuan Qi¹, Fan Li^{1

3

4

5

6}

Affiliations

¹ Department of Pathogenobiology, The Key Laboratory of Zoonosis, Chinese Ministry of Education, College of Basic Medicine, Jilin University, Changchun, China.
² Department of Ultrasonography, The Third Hospital of Jilin University, Changchun, China.
³ The Key Laboratory for Bionics Engineering, Ministry of Education, China, Jilin University, Changchun, China.
⁴ Engineering Research Center for Medical Biomaterials of Jilin Province, Jilin University, Changchun, China.
⁵ Key Laboratory for Biomedical Materials of Jilin Province, Jilin University, Changchun, China.
⁶ State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Urumqi, China.

Abstract

Background: Lung adenocarcinoma (LUAD) is challenging in clinical practice due to the poor understanding of molecular mechanisms and limited therapeutic targets. Herein, the work aimed to use bioinformatics to identify a promising molecular target for LUAD therapy.

Methods: Differentially expressed genes (DEGs) from the Cancer Genome Atlas (TCGA) dataset were used for a weighted gene co-expression network analysis (WGCNA) to screen the hub gene. After a prognostic estimation with meta-analysis and COX regression analysis, we performed a function analysis on the corresponding gene. The ESTIMATE and CIBERSORT methods were adopted to analyze the association of the hub gene with the tumor microenvironment (TME). A cohort of functional assays was conducted to establish the functional roles of the hub gene in A549 and PC-9 cells.

Results: Our screen identified KIF11 as a prognostic factor, which indicated the poor overall survival and the worse progression-free survival in LUAD patients. Additionally, KIF11 was primarily involved in cell cycle, TME alteration and tumor-infiltrating immune cells proportions. KIF11 knockdown exerted inhibitory effects on cell proliferation, migration, and invasion. Results of the flow cytometry analysis revealed that KIF11 knockdown induced a G2/M phase arrest and improved apoptosis in LUAD cells.

Conclusions: KIF11 is essential for LUAD cell proliferation and metastasis, and it may serve as an independent prognostic factor as well as a promising therapeutic target for LUAD patients.

Keywords: KIF11; bioinformatics; lung adenocarcinoma; prognosis; therapeutic target.