长链非编码 RNA LEMD1-AS1 通过增加 LEMD1 的表达并激活 PI3K-AKT 通路促进口腔鳞状细胞癌转移。
Long Noncoding RNA LEMD1-AS1 Increases LEMD1 Expression and Activates PI3K-AKT Pathway to Promote Metastasis in Oral Squamous Cell Carcinoma.
机构信息
Department of Oral and Maxillofacial Surgery, Center of Stomatology, Xiangya Hospital, Central South University, Changsha, China.
Research Center of Oral and Maxillofacial Tumor, Xiangya Hospital, Central South University, Changsha, China.
出版信息
Biomed Res Int. 2022 Aug 9;2022:3543948. doi: 10.1155/2022/3543948. eCollection 2022.
BACKGROUND
The survival rate of oral squamous cell carcinoma (OSCC) is only 50% due to a high incidence of metastasis. Long noncoding RNAs (lncRNAs) play a crucial role in OSCC genesis and progression, although their potential role in the metastasis of OSCC remains unclear.
METHODS
The transcriptome of 5 metastatic and 5 nonmetastatic OSCC samples were assessed by RNA sequencing. The biological functions and regulatory mechanisms of LEMD1-AS1 in OSCC were explored by in vitro and in vivo assays.
RESULTS
We identified 487 differentially expressed mRNAs (DEmRNAs) and 1507 differentially expressed lncRNAs (DElncRNAs) in OSCC with cervical lymph node (LN) metastasis relative to the nonmetastatic samples. In addition, both LEMD1-AS1 and its cognate LEMD1 were up-regulated in metastatic OSCC compared to nonmetastatic OSCC. Gain-of-function, loss-of-function, and rescue experiments indicated that LEMD1-AS1 upregulated LEMD1 to increase OSCC migration and invasion in vitro and in vivo. Mechanistically, LEMD1-AS1 stabilized LEMD1 and increased its mRNA and protein levels, and consequently activated the PI3K-AKT signaling pathway to facilitate OSCC metastasis.
CONCLUSIONS
We established the lncRNA-mRNA landscape of metastatic OSCC, which indicated that LEMD1-AS1 enhanced OSCC metastasis by stabilizing its antisense transcript LEMD1. Thus, LEMD1-AS1 is a potential biomarker for predicting metastasis, as well as a therapeutic target of OSCC.
背景
由于转移率高，口腔鳞状细胞癌（OSCC）的存活率仅为 50%。长链非编码 RNA（lncRNA）在 OSCC 的发生和发展中起着至关重要的作用，尽管它们在 OSCC 转移中的潜在作用尚不清楚。
方法
通过 RNA 测序评估了 5 个转移性和 5 个非转移性 OSCC 样本的转录组。通过体外和体内实验研究了 LEMD1-AS1 在 OSCC 中的生物学功能和调控机制。
结果
我们在 OSCC 伴颈部淋巴结（LN）转移的样本中鉴定出 487 个差异表达的 mRNAs（DEmRNAs）和 1507 个差异表达的 lncRNAs（DElncRNAs）。此外，与非转移性 OSCC 相比，转移性 OSCC 中 LEMD1-AS1 和其同源物 LEMD1 均上调。功能获得、功能丧失和挽救实验表明，LEMD1-AS1 上调 LEMD1 以增加 OSCC 在体外和体内的迁移和侵袭。在机制上，LEMD1-AS1 稳定 LEMD1，增加其 mRNA 和蛋白水平，进而激活 PI3K-AKT 信号通路，促进 OSCC 转移。
结论
我们建立了转移性 OSCC 的 lncRNA-mRNA 图谱，表明 LEMD1-AS1 通过稳定其反义转录本 LEMD1 增强 OSCC 转移。因此，LEMD1-AS1 是预测转移的潜在生物标志物，也是 OSCC 的治疗靶点。
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