Expression and clinical significance of FOXL2NB in colorectal cancer

doi:10.16352/j.issn.1001-6325.2023.06.0909

Abstract

Abstract: Objective To analyze the forkhead box L2 neighbor (FOXL2NB) expression in colorectal cancer (CRC) and its potential clinical significance, and to explore the role of FOXL2NB in CRC cells. Methods Real time qPCR and Western blot were used to analyze the expression of FOXL2NB in CRC tissues and cells. Transwell and CCK-8 assay were used to investigate the effect of FOXL2NB on the proliferation and migration in SW620 cell line. Kaplan-Meier and multivariate Cox regression analysis were used to evaluate the prognostic significance of FOXL2NB in CRC patients. CIBERSORT R package was used to calculate the correlation between FOXL2NB expression and immune cell infiltration in CRC tissues. limma R package was used to calculate the genes that significantly correlated with FOXL2NB expression. Results The mRNA and protein levels of FOXL2NB were significantly increased in CRC cell lines and tissues (P＜ 0.05). High level of FOXL2NB was associated with shorter overall survival and progression free survival in CRC patients (P＜ 0.05), which could be used as an independent risk factor for CRC prognosis (HR=2.27, 95% CI=1.78-2.9, P＜ 0.001). FOXL2NB knockdown inhibited the migration and proliferation of CRC cells. Cell adhesion molecules and tumor immune-related pathways were significantly enriched in CRC with high FOXL2NB expression, CD8⁺ T cells and activated dendritic cells were significantly increased, while M0 macrophages were significantly decreased. FOXL2NB expression was positively correlated with SCRT2, MGAT5B, SELENOV, FOXB1, KCNA4, LRRC14B and SLC32A1 genes. Conclusions FOXL2NB is highly expressed in CRC and potentially predicts poor prognosis. FOXL2NB might promote CRC cell proliferation and migration.

Key words: colorectal cancer, forkhead box, FOXL2NB, cell adhesion, tumor immunity

CLC Number:

R735.7

DU Feng, CHEN Yiyang, ZHANG Nan, XU Junxuan, NING Tingting, ZHU Shengtao, ZHANG Shutian. Expression and clinical significance of FOXL2NB in colorectal cancer[J]. Basic & Clinical Medicine, 2023, 43(6): 909-915.

References 12

[1]	Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: Globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. Cancer J Clin, 2021,71:209-249.
[2]	Ciardiello F, Ciardiello D, Martini G, et al. Clinical management of metastatic colorectal cancer in the era of precision medicine[J]. CA Cancer J Clin, 2022,72:372-401.
[3]	Gauthier L, Morel A, Anceriz N, et al. Multifunctional natural killer cell engagers targeting nkp46 trigger protective tumor immunity[J]. Cell, 2019,177:1701-1713.
[4]	Laissue P. The forkhead-box family of transcription factors: key molecular players in colorectal cancer pathogenesis[J]. Mol Cancer, 2019,18:5.doi:10.1186/s12943-019-0938-x
[5]	Zaiss D, Coffer PJ. Forkhead box transcription factors as context-dependent regulators of lymphocyte homeostasis[J]. Nat Rev Immunol, 2018,18:703-715.
[6]	Yoshida Y, Wang IC, Yoder HM, et al. The forkhead box M1 transcription factor contributes to the development and growth of mouse colorectal cancer[J]. Gastroenterology, 2007,132:1420-1431.
[7]	Du F, Qiao C, Li X, et al. Forkhead box K2 promotes human colorectal cancer metastasis by upregulating ZEB1 and EGFR[J]. Theranostics, 2019,9:3879-3902.
[8]	Liu J, Zhang Z, Li X, et al. Forkhead box C1 promotes colorectal cancer metastasis through transactivating ITGA7 and FGFR4 expression[J]. Oncogene, 2018,37:5477-5491.
[9]	Dai Y, Jiang Z, Qiu Y, et al. Identification of key carcinogenic genes in colon adenocarcinoma[J]. Iran J Public Health, 2022,51:364-374.
[10]	Fang Z, Huang H, Wang L, et al. Identification of the alpha linolenic acid metabolism-related signature associated with prognosis and the immune microenvironment in nasopharyngeal carcinoma[J]. Front Endocrinol (Lausanne), 2022,13:968984.doi:10.3389/fendo.2022.968984
[11]	Tian S, Meng G, Zhang W. A six-mRNA prognostic model to predict survival in head and neck squamous cell carcinoma[J]. Cancer Manag Res, 2019,11:131-142.
[12]	Egen JG, Ouyang W, Wu LC. Human anti-tumor immunity: Insights from immunotherapy clinical trials[J]. Immunity, 2020,52:36-54.

[1]	LU Huiying, WANG Jianguo. Downregulation of demethylase FTO inhibits proliferation of human liver cancer cell line HepG2 [J]. Basic & Clinical Medicine, 2024, 44(2): 185-191.
[2]	ZHANG Hailing, YANG Yu, ZHOU Qianqian, WANG Yuanjin, WANG Ting. Neutrophil NETs treated with microcystin-LR promote migration of colorectal cancer cell [J]. Basic & Clinical Medicine, 2023, 43(6): 967-973.
[3]	ZHANG Yanping, YAO Liuxu, DING Qiannan, HUANG Zeyong, LI Yuhong, HUANG Suqin. Influencing factors and the clinical significance of tumorigenesis rate in PDX model of colorectal cancer [J]. Basic & Clinical Medicine, 2023, 43(4): 596-602.
[4]	ZOU Jie, ZHANG Dede, TAO Yi, ZHAO Jing, WANG Qiong, XU Naijia. Puerarin attenuates the inflammatory response of vascular endothelial cells in KKAy mice [J]. Basic & Clinical Medicine, 2023, 43(3): 433-437.
[5]	WANG Fangfang, CAO Huiyuan, WANG Jing, WANG Ning, HUANG Guoliang. Up-regulation of miR-200c-5p inhibits proliferation of human colorectal cancer cell line SW480 [J]. Basic & Clinical Medicine, 2023, 43(2): 241-245.
[6]	YAO Liuxu, LI Yuhong, JIANG Zongming. Research progress of exosome lncRNA in liquid biopsy of colorectal cancer [J]. Basic & Clinical Medicine, 2023, 43(2): 317-321.
[7]	YU Hong, DING Lijie, LIU Houcong, WANG Jidong, DU Jihui. Detection and clinical application of VAR2 synthetic peptide specific binding to circulating tumor cells [J]. Basic & Clinical Medicine, 2023, 43(11): 1662-1667.
[8]	HOU Xinran, HOU Jingya, ZHANG Yaru, LI Haili. Research progress on the role of forkhead box protein M1 in brain glioma [J]. Basic & Clinical Medicine, 2023, 43(10): 1604-1607.
[9]	MENG Xuanyu, LIU Dihui, JIANG Shuo, GUAN Yaqun, LIANG Xiaodi. FOXP1 expression is increased after Stau1 knockdown of murine preadipocyte cell line 3T3-L1 [J]. Basic & Clinical Medicine, 2023, 43(1): 130-136.
[10]	ZHUANG Zhicheng, GUAN Guoxian. Ferroptosis in the treatment of colorectal cancer [J]. Basic & Clinical Medicine, 2023, 43(1): 174-177.
[11]	XIE Si-an, CHEN Yi-yang, XU Jun-xuan, NING Ting-ting, ZHANG Nan, ZHU Sheng-tao, ZHANG Shu-tian. Effect of PTOV1 expression on prognosis of colorectal cancer patients [J]. Basic & Clinical Medicine, 2022, 42(8): 1176-1181.
[12]	ZHANG Jian, ZHANG Tong, WANG Hong-wei, ZHANG Ji-hong, ZHANG Bao-zhen, DONG Xin-min. Up-regulation of miR-433 expression inhibits proliferation of colorectal cancer cell line in vitro [J]. Basic & Clinical Medicine, 2021, 41(8): 1127-1132.
[13]	YANG Xu-dong, YU Hong-liang, LI Jing, ZHAO Chun-hua. Macrophage J774A.1 exosome promotes the proliferation and migration of colorectal cancer cell lines MC38 and CT26 [J]. Basic & Clinical Medicine, 2021, 41(6): 799-804.
[14]	ZHOU Di-xia, LYU Hai-dong. Long non-coding RNA MCM3AP-AS1 targeted miR-876-5p promotes the proliferation and migration of colorectal cancer cell lines [J]. Basic & Clinical Medicine, 2021, 41(2): 225-232.
[15]	HUANG Bo, CHENG Bi-heng, XIE Mei-ting, LIU Shan-shan, WEI Min. FOXM1 promotes proliferation, migration and invasion of endometrial cancer cell line HEC-1B [J]. Basic & Clinical Medicine, 2021, 41(12): 1780-1785.