YBX1 Enhances Metastasis and Stemness by Transcriptionally Regulating MUC1 in Lung Adenocarcinoma

Abstract

Abnormal expression of the transcription factor Y-box-binding protein-1 (YBX1) is associated with the proliferation, migration, aggressiveness, and stem-like properties of various cancers. These characteristics contribute to the tumorigenesis and metastasis of cancer. We found that the expression levels of Mucin-1 (MUC1) and YBX1 were positively correlated in lung adenocarcinoma cells and lung adenocarcinoma tissue. Our retrospective cohort study of 176 lung adenocarcinoma patients after surgery showed that low expression of both YBX1 and MUC1 was an independent predictor of the prognosis and recurrence of lung adenocarcinoma. In lung adenocarcinoma cells, the silencing/overexpression of YBX1 caused a simultaneous change in MUC1, and MUC1 overexpression partially reversed the decreased tumor cell migration, aggressiveness, and stemness caused by YBX1 silencing. Moreover, chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays proved that MUC1 was the downstream target of YBX1 and that YBX1 bound to the -1480~-1476 position in the promoter region of MUC1 to regulate its transcription. Furthermore, in mouse xenograft models and a lung cancer metastasis model, MUC1, which is downstream of YBX1, partially reversed the decreased number and size of tumors caused by YBX1 silencing. In conclusion, our findings indicated a novel mechanism by which YBX1 promotes the stemness and metastasis of lung adenocarcinoma by targeting MUC1 and provided a combination approach for diagnosis different from traditional single tumor biomarkers to predict patient prognosis and provide clinical treatment targets.

YB-1 as an Oncoprotein: Functions, Regulation, Post-Translational Modifications, and Targeted Therapy

“…In melanoma, YB-1 promotes a highly invasive phenotype [ 60 ]. Additionally, YB-1 promotes the metastasis of liver cancer [ 61 ], gastric cancer [ 58 ], skin squamous cell carcinoma [ 62 ], spinal chordoma [ 46 ], ovarian cancer [ 63 ], prostate cancer [ 64 ], and lung adenocarcinoma [ 65 ]. Interestingly, one study showed that human YB-1 inhibited AKT-dependent oncogenic transformation in NIH3T3 [ 66 ].…”

Comprehensive Analysis of the Expression of the IGF2BPs gene family in Head and Neck Squamous Cell Carcinoma: Association with Prognostic Value and Tumor Immunity

“…IGF2BP1 stabilized the YBX1 by correlating with the Coding Region instability Determinant (CRD) 26 . Moreover, YBX1 was upregulated in lung adenocarcinoma and acted as an independent predictor of the prognosis and recurrence of lung adenocarcinoma 27 . The stabilization of YBX1 by IGF2BP1 may be a crucial mechanism in the onset and progression of the disease.…”

NCAPG stimulates lung adenocarcinoma cell stemness through aerobic glycolysis

“…The same number of cells (1000) were seeded into ultra‐low attachment culture dishes and cultured in RMPI‐1640 supplemented with 2% B27 (Thermo Fisher, USA), 20 ng/mL epidermal growth factor, and 10 ng/mL basic fibroblast growth factor (BD, USA) in 10% FBS for 10 days. Cell balls were observed with an inverted microscope and photographed, and the longest diameter was calculated by the scale size in the images using Image‐Pro Plus software 16 …”