Yi Tiezhong, Song Yicun, Zuo Lingling, Wang Siyun, Miao Jintian
Department of Gynecology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Department of Pathology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.
Front Oncol. 2021 Jun 25;11:646217. doi: 10.3389/fonc.2021.646217. eCollection 2021.
Increasing researches emphasize the importance of long non-coding RNAs (lncRNAs) in the development of endometrial cancer (EC). There is wide recognition that LINC00470 is a critical participant in the tumorigenesis of cancers such as gastric cancer and glioblastoma, but its possible effects on EC progression remain to be explored.
We collected EC tissues and cells, where the expression of LINC00470 was determined, and followed by the Kaplan-Meier analysis of EC patient survival. We next examined the effect of LINC00470 and phosphatase and tensin homolog (PTEN) on EC cell migration, invasion, tube formation , and angiogenesis in mice xenografted with tumor after gain- or loss-of-function treatments. RNA pull-down, Co-IP, and ChIP experiments were performed to analyze the targeting relationships among LINC00470, MYC and DNMT3a.
LINC00470 was aberrantly upregulated in EC and its high expression correlated to prognosis of EC patients. LINC00470 promoted invasiveness, migration, and angiogenesis of EC cells, and facilitated tumorigenesis and metastasis , but those effects were reversed by up-regulating PTEN. Functionally, LINC00470 bound to MYC in EC and that LINC00470 stimulated the binding of MYC to DNMT3a, and thus recruited DNMT3a through MYC to promote PTEN methylation.
Our findings revealed that LINC00470 stimulated PTEN methylation to inhibit its expression by MYC-induced recruitment of DNMT3a, thus aggravating EC.
越来越多的研究强调长链非编码RNA（lncRNAs）在子宫内膜癌（EC）发生发展中的重要性。人们普遍认识到LINC00470是胃癌和胶质母细胞瘤等癌症肿瘤发生的关键参与者，但其对EC进展的可能影响仍有待探索。
我们收集了EC组织和细胞，检测LINC00470的表达，随后对EC患者生存情况进行Kaplan-Meier分析。接下来，在功能获得或缺失处理后，我们检测了LINC00470和磷酸酶及张力蛋白同源物（PTEN）对EC细胞迁移、侵袭、管形成以及小鼠肿瘤异种移植模型中血管生成的影响。进行RNA下拉、免疫共沉淀和染色质免疫沉淀实验，以分析LINC00470、MYC和DNMT3a之间的靶向关系。
LINC00470在EC中异常上调，其高表达与EC患者的预后相关。LINC00470促进EC细胞的侵袭性、迁移和血管生成，并促进肿瘤发生和转移，但上调PTEN可逆转这些作用。在功能上，LINC00470在EC中与MYC结合，并且LINC00470刺激MYC与DNMT3a的结合，从而通过MYC招募DNMT3a以促进PTEN甲基化。
我们的研究结果表明，LINC00470通过MYC诱导招募DNMT3a刺激PTEN甲基化以抑制其表达，从而加重EC。
