Silencing of UAP1L1 inhibits proliferation and induces apoptosis in esophageal squamous cell carcinoma

• Published in: Molecular carcinogenesis 2021-03, Vol.60 (3), p.179-187
• Main Authors: Xiao, Xiaoxiong, Jiang, Lei, Hu, Huoli, Huang, Yunhe, Yang, Lun, Jiao, Yang, Wei, Guangxia
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; Aged; AKT protein; Animals; Apoptosis; Apoptosis - genetics; BAX protein; CD40 antigen; CD40L protein; Cell Line, Tumor; Cell Movement - genetics; Cell Proliferation - genetics; DIABLO protein; ESCC; Esophageal cancer; Esophageal Neoplasms - genetics; Esophageal Neoplasms - pathology; Esophageal Squamous Cell Carcinoma - genetics; Esophageal Squamous Cell Carcinoma - pathology; Esophagus; FasL protein; Female; Gene Expression Regulation, Neoplastic; Gene Silencing; Humans; Male; MAP kinase; Mice; Mice, Nude; Middle Aged; migration; N-Acetylglucosamine; Nucleotidyltransferases - genetics; Nucleotidyltransferases - metabolism; p53 Protein; proliferation; Squamous cell carcinoma; Tumors; UAP1L1; Up-Regulation; Xenograft Model Antitumor Assays; Xenografts
• ISSN: 0899-1987; 1098-2744
• DOI: 10.1002/mc.23278

Esophageal squamous cell carcinoma (ESCC) is recognized as one of the malignant tumors with poor prognosis. UAP1L1 (UDP‐N‐acetylglucosamine‐1‐like‐1) affects numerous biological processes, which is a key regulator of the development of malignant tumors. The biological function and molecular mechanism of UAP1L1 in ESCC were explored in this study. The relationship between UAP1L1 and ESCC was analyzed by immunohistochemical staining, revealing the high expression of UAP1L1 in ESCC. Importantly, the increased expression of UAP1L1 indicated the deterioration of patients’ condition, which has clinical significance. Furthermore, the loss‐of‐function assays demonstrated that knockdown of UAP1L1 inhibited the progression of ESCC on suppressing proliferation, hindering migration, and enhancing apoptosis in vitro. Moreover, the apoptosis of ESCC cells was induced by knockdown of UAP1L1 via regulating a variety of apoptosis‐related proteins, such as upregulation of Bax, CD40, CD40L, Fas, FasL, IGFBP‐6, p21, p27, p53, and SMAC. Additionally, further investigation indicated that UAP1L1 by affecting the PI3K/Akt, CCND1, and MAPK promotes the progression of ESCC. In vivo xenograft model further confirmed that knockdown of UAP1L1 inhibited the development of ESCC. In conclusion, UAP1L1 was involved in the development and progression of ESCC, which may provide a powerful target for future molecular therapies.