Long noncoding RNA CDKN2B‐AS1 silencing protects against esophageal cancer cell invasion and migration by inactivating the TFAP2A/FSCN1 axis

Abstract

Esophageal cancer (EC) is the most aggressive malignancy in the gastrointestinal tract.Long noncoding RNA cyclin-dependent kinase inhibitor 2 B antisense RNA 1 (CDKN2B-AS1) is implicated in EC development. However, the specific mechanisms involved remain poorly defined. Therefore, this research aimed to explore the mechanism of action of CDKN2B-AS1 in EC. Quantitative real-time polymerase chain reaction was conducted to measure CDKN2B-AS1 expression in EC cells and western blotting was utilized to evaluate transcription factor AP-2 alpha (TFAP2A) and fascin actin-bundling protein 1 (FSCN1) expression. After gain-of-function and loss-of-function assays, cell proliferation, migration, invasion, apoptosis, and apoptosis-related protein expression were assessed using cell counting kit-8, scratch tests, Transwell assays, flow cytometry, and western blotting, respectively. The binding relationship between CDKN2B-AS1 and TFAP2A was assessed by RNA immunoprecipitation and RNA pull-down assays. The binding relationship between TFAP2A and FSCN1 was evaluated using dual-luciferase reporter and chromatin immunoprecipitation assays. Tumor xenografts from nude mice were used for in vivo verification. CDKN2B-AS1, TFAP2A, and FSCN1 were upregulated in EC cells. Mechanistically, CDKN2B-AS1 transcriptionally activated FSCN1 by recruiting TFAP2A to the FSCN1 promoter. Silencing CDKN2B-AS1 or TFAP2A suppressed EC cell proliferative, migrating, and invasive properties and augmented apoptosis. TFAP2A was bound to CDKN2B-AS1 and the FSCN1 promoter. Overexpression of TFAP2A or FSCN1 abolished the effects of CDKN2B-AS1-silencing on EC cell function. CDKN2B-AS1 silencing curtailed tumorigenesis in nude mice, which was nullified by the upregulation of TFAP2A or FSCN1. Our findings demonstrated the antioncogenic effects of silencing CDKN2B-AS1 in EC through inactivation of the TFAP2A/FSCN1 axis.

Potential prognosis and immunotherapy predictor TFAP2A in pan-cancer

“…TFAP2A expression is significantly higher in most cancer types except ACC, PRAD, Sarcoma (SARC), Testicular germ cell tumors (TGCT), and THCA, which is consistent with the analysis from the TIMER2 database and those in previous studies, such as in CHOL, Esophageal cancer (EC), Gastric cancer (GC), HNSC, Non-small cell lung cancers (NSCLC), OC, etc. [32,[37][38][39][40][41], suggests TFAP2A indeed promote oncogenesis and tumor progression. As we know, proteoforms are molecular actuators of gene function, so we explored the HPA database to obtain Immunohistochemistry (IHC) images.…”

TFAP2A promotes cervical cancer via a positive feedback pathway with PD‑L1

“…In nasopharyngeal carcinoma, TFAP2A overexpression has been shown to be positively associated with tumor stage, local infiltration and a decreased overall survival, and TFAP2 silencing results in a slower proliferation of cancer cells ( 8 ). The silencing of TFAP2A has been shown to inhibit the proliferation, migration and invasiveness of esophageal cancer cells, and to enhance apoptosis ( 28 ). The increased expression of TFAP2A has been demonstrated in gallbladder cancer, and its inhibition reduces the proliferation, migration and invasion of gallbladder cancer cells ( 29 ).…”