DLEU1 promotes cell survival by preventing DYNLL1 degradation in esophageal squamous cell carcinoma

• Published in: Journal of translational medicine 2022-05, Vol.20 (1), p.245-245, Article 245
• Main Authors: Li, Qihang, Zhang, Zhiyu, Jiang, HongChao, Hou, Jun, Chai, Yuhang, Nan, Hongxing, Li, Feng, Wang, Lianghai
• Format: Article
• Language: English
• Subjects: Apoptosis; BCL2; Biotechnology; Cell cycle; Cell death; Cell growth; Cell Line, Tumor; Cell survival; Cell Survival - genetics; Cisplatin; Cytoplasmic Dyneins - genetics; Development and progression; Dosage and administration; Esophageal cancer; Esophageal Neoplasms - genetics; Esophageal Neoplasms - pathology; Esophageal Squamous Cell Carcinoma - genetics; Esophageal Squamous Cell Carcinoma - pathology; Gene expression; Gene Expression Regulation, Neoplastic; Humans; Immunoprecipitation; Leukemia; lncRNA; Mass spectrometry; Medical prognosis; Non-coding RNA; Prevention; Proteasomes; Proteins; RNA polymerase; RNA, Long Noncoding - genetics; RNF114; Scientific imaging; Squamous cell carcinoma; Statistical analysis; Therapeutic targets; Tumors; Ubiquitination
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/s12967-022-03449-w

Emerging evidence has highlighted the critical roles of long noncoding RNAs (lncRNAs) in tumor development and progression. However, the biological functions and underlying mechanisms of DLEU1 in esophageal squamous cell carcinoma (ESCC) remain unclear. LncRNA expression in ESCC tissues was explored using lncRNA microarray datasets. The functional roles of DLEU1 in ESCC were demonstrated by a series of in vitro and in vivo experiments. RNA pull-down and immunoprecipitation assays were performed to demonstrate the potential mechanisms of DLEU1. In a screen for differentially expressed lncRNAs in ESCC, we determined that DLEU1 was one of the most overexpressed lncRNAs in ESCC tissues and that upregulated DLEU1 expression was associated with a worse prognosis. Functional assays showed that DLEU1 promoted tumor growth by inhibiting cell apoptosis. Mechanistically, DLEU1 could bind and stabilize DYNLL1 by interfering with RNF114-mediated ubiquitination and proteasomal degradation. The DLEU1/DYNLL1 axis subsequently upregulated antiapoptotic BCL2 and promoted cell survival. Furthermore, DLEU1 upregulation was at least partly facilitated by promoter hypomethylation. Notably, targeting DLEU1 sensitized ESCC cells to cisplatin-induced death. Our findings suggest that DLEU1-mediated stabilization of DYNLL1 is critical for cell survival and that the DLEU1/DYNLL1 axis may be a promising therapeutic target for ESCC.