Esophageal squamous cell carcinoma (ESCC) is characterized by high morbidity and mortality. Circular RNAs (circRNAs) play an important role in tumor progression. We discovered an aberrantly expressed circRNA (hsa_circ_0021727) in patients with ESCC. However, the mechanism of action of hsa_circ_0021727 in tumors is unclear. The present study aimed to investigate the biological role of hsa_circ_0021727 and its mechanism in ESCC progression. We screened for the expression of hsa_circ_0021727 in ESCC patients. Patients with ESCC with high expression of hsa_circ_0021727 had shorter survival than those with low expression. Hsa_circ_0021727 promoted the proliferation, invasion, and migration of ESCC cells. However, miR-23b-5p inhibited this ability of hsa_circ_0021727. MiR-23b-5p acts by targeting TAK1-binding protein 1 (TAB1). Upregulation of TAB1 can activate the nuclear factor kappa B (NFκB) pathway. Hsa_circ_0021727 promoted ESCC progression by activating TAB1/NFκB pathway by sponging miR-23b-5p. In addition, in vivo experiments also confirmed that hsa_circ_0021727 could promote the proliferation, invasion, and migration of ESCC cells. In short, hsa_circ_0021727 promotes ESCC progression by targeting miR-23b-5p to activate the TAB1/NFκB pathway. These findings might provide potential targets to treat ESCC.

Background The RING finger (RNF) proteins are a large group of ubiquitin ligases whose aberrant expression is often associated with disease progression. This study examines the function of RNF protein 182 (RNF182) in lung adenocarcinoma (LUAD) cells and its impact on p65 and programmed death ligand 1 (PDL1) regulation. Methods Expression of RNF182, p65, and PDL1 in LUAD tissues and cells was measured using immunohistochemistry, reverse transcription quantitative polymerase chain reaction (RT‐qPCR), and/or western blot (WB) assays. LUAD cells were induced to overexpress RNF182 and p65, followed by cell counting kit‐8, colony formation, Transwell, and flow cytometry assays to evaluate the cells’ malignant phenotype. Coimmunoprecipitation and WB assays were used to verify RNF182's effect on p65 ubiquitination. Chromatin immunoprecipitation‐qPCR and luciferase assays were used to analyze p65's transcriptional regulation of PDL1. Coculture of LUAD with CD8+ cytotoxic T cells was performed to detect lactate dehydrogenase release and interferon‐γ and interleukin‐2 concentrations. LUAD cells were implanted in mice to analyze tumorigenicity. Results RNF182 was poorly expressed, while p65 and PDL1 were highly expressed in LUAD tissues and cells. RNF182 overexpression suppressed the malignant properties of LUAD cells, and it promoted p65 ubiquitination and protein degradation. p65 activated PDL1 transcription. Overexpression of RNF182 suppressed the PDL1 expression, increased the cytotoxicity in LUAD cells cocultured with CD8+ T cells, and suppressed the tumorigenesis of cancer cells in vivo. However, these tumor‐suppressive effects of RNF182 on LUAD cells were blocked by p65 restoration. Conclusion This research demonstrates that RNF182 induces p65 ubiquitination to suppress PDL1 transcription and immunosuppression in LUAD.

Background: The morbidity and mortality of esophageal squamous cell carcinoma (ESCC) remain high globally. Circular RNAs (circRNAs) play an important role in tumor progression. We discovered a novel aberrantly expressed circRNA (hsa_circ_0021727) in ESCC patients. However, the mechanism of hsa_circ_0021727 in tumors is still not elucidated. The purpose of this article is to investigate the biological role of hsa_circ_0021727 and its role in ESCC progression.Methods: Microarray analysis was used to screen diferentially expressed novel circRNAs.qRT-PCR,RNA-ISH and FISH were used to analyze the expression and localization of hsa_circ_0021727.MTT, colony formation, EdU, transwell assay, three-dimensional (3D) spheroid invasion assays and wound healing assays were used to describe biological effects on ESCC cells.Xenograft experiment and tail vein injection experiment were used to analyze tumor growth and metastasis in vivo.RNA-sequencing was used to identify hsa_circ_0021727 downstream targets.Western blot was used to detect the downstream protein expression of hsa_circ_0021727.RNA pulldown and dual luciferase experiments were used to evaluate the interaction of hsa_circ_0021727, miR-23b-5p and TAB1.Results: We screened a novel circRNA (hsa_circ_0021727) whose expression was upregulated in ESCC patients.ESCC patients with high expression of hsa_circ_0021727 had shorter survival time.Hsa_circ_0021727 promoted the proliferation, invasion and migration of ESCC cells. However, miR-23b-5p inhibited this ability of hsa_circ_0021727. MiR-23b-5p acts by targeting TAB1. In conclusion, hsa_circ_0021727 promoted ESCC progression by upregulating the expression of TAK1-binding protein 1(TAB1) via "sponge adsorption" of miR-23b-5p. In addition, in vivo experiments also confirmed that hsa_circ_0021727 can promote the proliferation, invasion and migration of ESCC cells.Conclusions：Hsa_circ_0021727 (circ_CD44) promotes ESCC progression by targeting miR-23b-5p to activate the TAB1/NFκB pathway.These findings may provide potential targets for the treatment of ESCC.