Title:YBX1, Targeted By Microrna-382-5p, Promotes Laryngeal Squamous Cell
Carcinoma Progression via Modulating RAS/MAPK Signaling
Volume: 19
Issue: 2
Author(s): Wen Zeng, Yiyun Pan, Hailong Chen, Xianhua Lei and Xiangmin Zhang*
Affiliation:
- Department of Head and Neck Surgery, Ganzhou Cancer Hospital, Jiangxi Province, People’s Republic of China
- Department of Otolaryngology,
Longgang E.N.T hospital & Shenzhen Key Laboratory of E.N.T, Institute of E.N.T Shenzhen, Guangdong Province, People’s
Republic of China
Keywords:
Laryngeal cancer, squamous cell carcinoma, microRNA, Y-box binding protein-1, Ras signaling, mitogenactivated protein kinase.
Abstract:
Background: Laryngeal squamous cell carcinoma (LSCC) is the most common cancer
of head and neck cancer. Y-box binding protein-1 (YBX1) has tumor-promoting effects in some
types of cancers. However, its role in LSCC remains unknown. This study set out to identify the
role of YBX1 in LSCC.
Methods: Bioinformatics analysis of the Gene Expression Omnibus (GEO) database and our cohort
data were used to explore the association of YBX1 expression with clinicopathological factors
in LSCC. Then, cells with stably or transiently transfected with plasmid or siRNA were constructed
to assess the effect of loss and gain of YBX1 on the biological phenotypes of LSCC cells
in vitro. In addition, subcutaneous xenograft and orthotopic liver tumor mouse models were constructed
for validation. The interrogated miRNA databases and subsequent luciferase reporter assays
were used to confirm the miR-382-5p target of YBX1. At last, KEGG enrichment annotation
from TGCA data was used for downstream analyses of miR-382-5p/YBX1 and verified by PCR
and Western immunoblotting.
Results: The results showed that significant upregulation of YBX1 in LSCC tumors was correlated
with advanced TNM stage and poor prognosis. Knockdown of YBX1 markedly impaired the
proliferative, invasive, and migratory activity of Tu212 cells. We confirmed that miR-382-5p targets
YBX1 to mediate LSCC progression both in vitro and in vivo. We further confirmed that
miR-382-5p/YBX1 modulated the Ras/MAPK signaling axis to regulate the progression of LSCC.
Conclusion: Together, our results indicated that YBX1 is an important promoter of LSCC progression.
And miR-382-5p/YBX1/RAS/MAPK signaling pathway can be perceived as a promising
target in the treatment of LSCC.
