Department of Oral and Maxillofacial Surgery, Hospital of Stomatology, Jilin University, Changchun, Jilin 130021, P.R. China.
Department of Orthodontics, Hospital of Stomatology, Jilin University, Changchun, Jilin 130021, P.R. China.
Oncol Rep. 2021 Mar;45(3):1094-1104. doi: 10.3892/or.2020.7908. Epub 2020 Dec 24.
Long non‑coding RNA (lncRNA) actin filament‑associated protein 1 antisense RNA 1 (AFAP1‑AS1) has been reported to serve important roles in multiple types of cancer. However, the biological function and underlying mechanism of AFAP1‑AS1 in oral squamous cell carcinoma (OSCC) remain largely unknown. The present study aimed to investigate the biological roles and clarify the potential mechanism of AFAP1‑AS1 in OSCC. The expression levels of AFAP1‑AS1 in OSCC tissues and cells were determined using reverse transcription‑quantitative PCR. Cell proliferation, colony formation, migration and invasion were analyzed using Cell Counting Kit‑8, colony formation, wound healing and Transwell invasion assays, respectively. The potential binding between AFAP1‑AS1 and microRNA (miR)‑145 was validated using dual luciferase reporter and RNA pull‑down assays. A xenograft tumor model was established to evaluate the effect of AFAP1‑AS1 in vivo. The results revealed that AFAP1‑AS1 expression levels were markedly upregulated in OSCC tissues and cells. In addition, patients with OSCC with high expression levels of AFAP1‑AS1 had a poor prognosis. Functionally, the knockdown of AFAP1‑AS1 in OSCC cells significantly inhibited cell proliferation, migration and invasion in vitro. Similarly, in vivo AFAP1‑AS1 knockdown prevented tumor growth and reduced tumor size and weight. Mechanistically, AFAP1‑AS1 was discovered to regulate the expression levels of Homeobox A1 (HOXA1) by competing with miR‑145. The inhibition of miR‑145 partially attenuated the inhibitory effects of AFAP1‑AS1 knockdown on OSCC cells. In conclusion, the findings of the present study suggested that AFAP1‑AS1 may promote the progression of OSCC by regulating the miR‑145/HOXA1 axis.
长链非编码 RNA（lncRNA）肌动蛋白丝相关蛋白 1 反义 RNA 1（AFAP1-AS1）已被报道在多种类型的癌症中发挥重要作用。然而，AFAP1-AS1 在口腔鳞状细胞癌（OSCC）中的生物学功能和潜在机制仍在很大程度上未知。本研究旨在探讨 AFAP1-AS1 在 OSCC 中的生物学作用，并阐明其潜在机制。采用逆转录-定量 PCR 检测 OSCC 组织和细胞中 AFAP1-AS1 的表达水平。通过细胞计数试剂盒-8 检测、集落形成实验、划痕愈合实验和 Transwell 侵袭实验分别分析细胞增殖、集落形成、迁移和侵袭能力。采用双荧光素酶报告基因和 RNA 下拉实验验证 AFAP1-AS1 与 microRNA（miR）-145 之间的潜在结合。建立异种移植肿瘤模型评估 AFAP1-AS1 在体内的作用。结果显示，AFAP1-AS1 在 OSCC 组织和细胞中的表达水平明显上调。此外，AFAP1-AS1 高表达的 OSCC 患者预后较差。功能上，OSCC 细胞中 AFAP1-AS1 的敲低显著抑制了细胞在体外的增殖、迁移和侵袭。同样，体内 AFAP1-AS1 敲低可防止肿瘤生长并减少肿瘤的大小和重量。机制上，发现 AFAP1-AS1 通过与 miR-145 竞争来调节同源盒 A1（HOXA1）的表达水平。miR-145 的抑制部分减弱了 AFAP1-AS1 敲低对 OSCC 细胞的抑制作用。综上所述，本研究结果表明，AFAP1-AS1 可能通过调节 miR-145/HOXA1 轴促进 OSCC 的进展。
