Yin Yang 1-stimulated long noncoding RNA bladder cancer-associated transcript 1 upregulation facilitates esophageal carcinoma progression via the microRNA-5590-3p/programmed cell death-ligand 1 pathway

Abstract

Esophageal carcinoma (EC) is a common gastrointestinal malignancy that poses a threat to public health worldwide. Long noncoding RNA (lncRNA) bladder cancer-associated transcript 1 (BLACAT1) exerts a tumorigenic role in several malignant tumors; nevertheless, its function in EC remains largely unknown. Besides, programmed cell death-ligand 1 (PD-L1), an oncogene in numerous human cancers, has been identified as a therapeutic target for EC. Therefore, we intended to explore the potential regulatory network involving BLACAT1 and PD-L1 in EC. In this study, we observed increased BLACAT1 and PD-L1 levels in EC tissues and EC cell lines. Moreover, YY1 could activate BLACAT1 transcription in EC cells (TE-1 and EC9706). In addition, in vitro and in vivo experiments demonstrated that BLACAT1 facilitated EC cell proliferation and metastasis and EC tumor growth. Also, the effects of BLACAT1 silencing on EC cell functions were partially reversed by PD-L1 overexpression. Besides, it was identified that BLACAT1 competed with PD-L1 to bind to miR-5590-3p in EC cells. Furthermore, miR-5590-3p suppression could abrogate the functional effects of BLACAT1 knockdown on EC cells; while PD-L1 silencing partly abolished the promoting effects of miR-5590-3p suppression on the biological functions of EC cells. To sum up, YY1-induced BLACAT1 accelerated EC progression via regulating the miR-5590-3p/PD-L1 axis.

MicroRNAs as regulators of immune checkpoints in cancer immunotherapy: targeting PD-1/PD-L1 and CTLA-4 pathways

“…Also, BLACAT1 promotes the growth, expansion, and metastasis of esophageal cancer cells by competing with PD-L1 to bind to miR-5590-3p in these cells. Moreover, the study found that silencing PD-L1 partially reversed the promoting effects of BLACAT1 [ 144 ].…”

Crosstalk between YY1 and lncRNAs in cancer: A review

“…in esophageal squamous cell carcinoma, YY1 has been confirmed to bind to the hypomethylation promoter region of ESCCAL-1, [ 54 ] and YY1-induced BLACAT1 was able to compete with PD-L1 for binding to miR-5590-3p in esophageal cancer cells. [ 55 ] FOXP4-AS1 can up-regulate FOXP4 expression and promote the proliferation of esophageal squamous cell carcinoma by sponging miR-3184-5p, and YY1 can promote the activation transcription of FOXP4-AS1. [ 56 ] YY1 promotes the progress of laryngeal squamous cell carcinoma and telomerase activity by inhibiting the stability of GAS5-dependent p53 or reducing the stability of p53 by binding to P300.…”