FOXD2-AS1 promotes malignant cell behavior in oral squamous cell carcinoma via the miR-378 g/CRABP2 axis

• Published in: BMC oral health 2024-05, Vol.24 (1), p.625-13, Article 625
• Main Authors: Guo, Shaoyong, Huang, Bixia, You, Zhisong, Luo, Zhenzhi, Xu, Da, Zhang, Jieru, Lin, Jialin
• Format: Article
• Language: English
• Subjects: Apoptosis; Apoptosis - genetics; Bioinformatics; Biomarkers; Cancer therapies; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; Cell growth; Cell Line, Tumor; Cell migration; Cell Movement - genetics; Cell proliferation; Cell Proliferation - genetics; ceRNA network; Chemotherapy; Development and progression; DNA nucleotidylexotransferase; DNA polymerases; Functional experiments; Gene expression; Gene Expression Regulation, Neoplastic; Genes; Genetic transcription; Humans; Immunoprecipitation; Invasion; lncRNA; Luciferase; Malignancy; Medical prognosis; MicroRNA; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; Migration; miRNA; Mouth Neoplasms - genetics; Mouth Neoplasms - metabolism; Mouth Neoplasms - pathology; Non-coding RNA; Oral cancer; Oral carcinoma; Oral cavity; Oral squamous cell carcinoma; Protein binding; Quality of life; Radiation therapy; Reagents; Retinoic acid; Reverse transcription; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Scientific equipment and supplies industry; Squamous cell carcinoma; Surgery; Tumors; Wound healing
• ISSN: 1472-6831; 1472-6831
• DOI: 10.1186/s12903-024-04388-2

Oral squamous cell cancer (OSCC) is a prevalent malignancy in oral cavity, accounting for nearly 90% of oral malignancies. It ranks sixth among the most common types of cancer worldwide and is responsible for approximately 145,000 deaths each year. It is widely accepted that noncoding RNAs participate cancer development in competitive regulatory interaction, knowing as competing endogenous RNA (ceRNA) network, whereby long non-coding RNA (lncRNA) function as decoys of microRNAs to regulate gene expression. LncRNA FOXD2-AS1 was reported to exert an oncogenic role in OSCC. Nevertheless, the ceRNA network mediated by FOXD2-AS1 was not investigated yet. This study aimed to explore the effect of FOXD2-AS1 on OSCC cell process and the underlying ceRNA mechanism. FOXD2-AS1 expression in OSCC cells were determined via reverse transcription and quantitative polymerase chain reaction. Short hairpin RNA targeting FOXD2-AS1 was transfected into OSCC cells to silence FOXD2-AS1 expression. Then, loss-of-function experiments (n = 3 each assay) were performed to measure cell proliferation, apoptosis, migration, and invasion using colony formation, TdT-mediated dUTP Nick-End Labeling, wound healing and Transwell assays, respectively. RNA binding relation was verified by RNA immunoprecipitation and luciferase reporter assays. Rescue experiments were designed to validate whether FOXD2-AS1 affects cell behavior via the gene cellular retinoic acid binding protein 2 (CRABP2). Statistics were processed by GraphPad Prism 6.0 Software and SPSS software. FOXD2-AS1 was significantly upregulated in Cal27 and SCC9 cells (6.8 and 6.4 folds). In response to FOXD2-AS1 knockout, OSCC cell proliferation, migration and invasion were suppressed (approximately 50% decrease) while OSCC cell apoptosis was enhanced (more than two-fold increase). FOXD2-AS1 interacted with miR-378 g to alter CRABP2 expression. CRABP2 upregulation partly rescued (*p