Department of Oral and Maxillofacial Surgery, Changyi People's Hospital, Weifang 261300, Shandong, China.
Health Management Center, Shandong Provincial Qianfoshan Hospital, The First Affiliated Hospital of Shandong First Medical University, Jinan 250014, Shandong, China.
Oral Surg Oral Med Oral Pathol Oral Radiol. 2023 Feb;135(2):257-267. doi: 10.1016/j.oooo.2022.08.016. Epub 2022 Sep 7.
Ephrin receptor A2 (EphA2) was reported to be related to the tumorigenesis of salivary adenoid cystic carcinoma (SACC), which is a rare malignancy accounting for less than 1% of all oral and maxillofacial tumors. This research aimed to assess the molecular mechanisms of EphA2 in SACC.
The expression of long non-coding RNA human leukocyte antigen complex group 11 (HCG11), microRNA-1297 (miR-1297), and EphA2 in SACC cell lines compared with normal human salivary gland (HSG) cell line was measured by reverse transcription-quantitative polymerase chain reaction. EphA2 protein level was detected by western blot. 5-ethynyl-2'-deoxyuridine (EdU), colony formation, Transwell, and wounding healing experiments were applied to evaluate SACC cell proliferation, migration, and invasion. The relationship among HCG11, miR-1297, and EphA2 was confirmed by luciferase reporter, RNA pulldown, and RNA immunoprecipitation experiments.
HCG11 and EphA2 were downregulated while miR-1297 was upregulated in SACC cells. EphA2 overexpression suppressed SACC cell proliferation, migration, and invasion. HCG11 bound to miR-1297 to reduce the inhibition of miR-1297 on EphA2 expression. EphA2 knockdown reversed the suppression of HCG11 overexpression on SACC cell phenotypes.
This study identified the HCG11/miR-1297/EphA2 regulatory axis in SACC, which might provide novel therapeutic targets for SACC.
Eph 受体 A2（EphA2）被报道与唾液腺腺样囊性癌（SACC）的发生有关，SACC 是一种罕见的恶性肿瘤，占所有口腔颌面部肿瘤的比例不到 1%。本研究旨在评估 EphA2 在 SACC 中的分子机制。
通过逆转录定量聚合酶链反应测量 SACC 细胞系与正常人类唾液腺（HSG）细胞系中长链非编码 RNA 人类白细胞抗原复合物 11（HCG11）、miR-1297（miR-1297）和 EphA2 的表达。通过 Western blot 检测 EphA2 蛋白水平。应用 5-乙炔基-2'-脱氧尿苷（EdU）、集落形成、Transwell 和划痕愈合实验来评估 SACC 细胞的增殖、迁移和侵袭。通过荧光素酶报告、RNA 下拉和 RNA 免疫沉淀实验证实了 HCG11、miR-1297 和 EphA2 之间的关系。
SACC 细胞中 HCG11 和 EphA2 下调，而 miR-1297 上调。EphA2 过表达抑制 SACC 细胞增殖、迁移和侵袭。HCG11 与 miR-1297 结合，减少 miR-1297 对 EphA2 表达的抑制作用。EphA2 敲低逆转了 HCG11 过表达对 SACC 细胞表型的抑制作用。
本研究鉴定了 SACC 中的 HCG11/miR-1297/EphA2 调节轴，这可能为 SACC 提供新的治疗靶点。
