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

Abstract

Background 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. Methods 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. Results 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. Conclusions 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.

Single-Cell Transcriptomic, hdWGCNA, and Machine Learning reveal the Role of DYNLL1 in Lung Adenocarcinoma within Epithelial Cells

“…DLEU1 stabilizes DYNLL1 by interfering with RNF114-mediated ubiquitination and proteasomal degradation of DYNLL1, subsequently upregulating the anti-apoptotic protein BCL2, thereby inhibiting cell apoptosis. This discovery not only reveals the significant biological function of DLEU1 in ESCC but also suggests that the DLEU1/DYNLL1 axis could be a promising target for ESCC treatment [42].Moreover, studies have found that DYNLL1 forms a complex with the mitochondrial cytochrome oxidase Cox4i1, crucial for clearing intracellular pathogens. The dissociation of the DYNLL1-Cox4i1 complex is key to releasing mitochondrial reactive oxygen species and regulating the intracellular proliferation of the bacterium Listeria monocytogenes.…”

Roles of long non‑coding RNAs in esophageal cell squamous carcinoma (Review)

“…This interaction promoted myeloid cell leukemia 1 (Mcl-1) splicing and facilitated Mcl-1L isoform switching, promoting proliferation, migration and invasion in TE-1 and KYSE170 cells, as well as inhibiting apoptosis ( 91 ). DLEU1 bound to dynein light chain LC8-type 1, inhibiting its ubiquitination and degradation by ring finger protein 114, thereby inhibiting apoptosis in KYSE410 and EC109 cells, promoting cisplatin/cis-diamminedichloroplatinum (CDDP) resistance and conferring resistance in CDX (KYSE410) cells ( 92 ). GK intronic transcript 1 bound to mitogen-activated protein kinase 1, preventing its interaction with dual specificity phosphatase 6 and activating the ERK/MAPK signaling pathway, promoting proliferation, invasion and migration in TE-1 and TE-10 cells, as well as being associated with clinical staging and prognosis ( 23 ).…”