Department of Oral and Maxillofacial Surgery, Xiangya Stomatological Hospital, Central South University, Changsha, Hunan, China.
Department of Oncology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
J Oral Pathol Med. 2020 Oct;49(9):865-875. doi: 10.1111/jop.13047. Epub 2020 Jun 20.
Non-coding RNAs play a critical role in the occurrence and development of oral cancer. The present study is aimed to identify long non-coding RNA (lncRNA) that might be novel effective targets for the treatments of oral cancer and the underlying mechanism.
The microarray profiling and RNA-sequencing analysis were performed to identify lncRNAs related to oral cancer development, and lncRNA DNM3OS was selected. DNM3OS knockdown was generated in cancer cell lines, and the specific effects of DNM3OS knockdown on cell phenotype were examined. DNM3OS targeted miRNA and miRNA targeted downstream mRNA were selected, the predicted bindings were verified, and the specific effects of miRNA on oral cancer cells were examined. Finally, the dynamic effects of DNM3OS and miRNA on target mRNA expression and oral cancer cell phenotype were examined.
DNM3OS was upregulated in oral cancer tissues and cells. DNM3OS knockdown in CAL27 and SCC-9 cells inhibited cell viability and migration. DNM3OS targeted miR-204-5p to inhibit miR-204-5p expression. miR-204-5p overexpression suppressed oral cancer cell aggressiveness. miR-204-5p targeted HIP1 to inhibit HIP1 expression. HIP1 knockdown inhibited oral cancer cell viability and migration. The effects of DNM3OS knockdown were significantly reversed by miR-204-5p inhibition. Within oral carcinoma tissue samples, expression of DNM3OS and HIP1 was increased whereas the miR-204-5p expression was downregulated; miR-204-5p had a negative correlation with DNM3OS and HIP1, respectively, while DNM3OS and HIP1 were positively correlated with each other.
Long non-coding RNA DNM3OS, miR-204-5p, and HIP1 form an axis that modulates oral cancer cell viability and migration.
非编码 RNA 在口腔癌的发生和发展中起着关键作用。本研究旨在鉴定可能成为口腔癌治疗新靶点的长非编码 RNA（lncRNA）及其潜在机制。
通过微阵列分析和 RNA 测序分析，鉴定与口腔癌发生发展相关的 lncRNA，选择 lncRNA DNM3OS。在癌细胞系中进行 DNM3OS 敲低，检测 DNM3OS 敲低对细胞表型的具体影响。选择 DNM3OS 靶向的 miRNA 和 miRNA 靶向的下游 mRNA，预测结合并检测 miRNA 对口腔癌细胞的具体影响。最后，检测 DNM3OS 和 miRNA 对靶 mRNA 表达和口腔癌细胞表型的动态影响。
DNM3OS 在口腔癌组织和细胞中上调。CAL27 和 SCC-9 细胞中 DNM3OS 敲低抑制细胞活力和迁移。DNM3OS 靶向 miR-204-5p 抑制 miR-204-5p 表达。miR-204-5p 过表达抑制口腔癌细胞侵袭性。miR-204-5p 靶向 HIP1 抑制 HIP1 表达。HIP1 敲低抑制口腔癌细胞活力和迁移。miR-204-5p 抑制可显著逆转 DNM3OS 敲低的作用。在口腔癌组织样本中，DNM3OS 和 HIP1 的表达增加，而 miR-204-5p 的表达下调；miR-204-5p 与 DNM3OS 和 HIP1 分别呈负相关，而 DNM3OS 和 HIP1 呈正相关。
长非编码 RNA DNM3OS、miR-204-5p 和 HIP1 形成轴，调节口腔癌细胞活力和迁移。
