Upregulation of the lncRNA Meg3 induces autophagy to inhibit tumorigenesis and progression of epithelial ovarian carcinoma by regulating activity of ATG3.
Upregulation of the lncRNA Meg3 induces autophagy to inhibit tumorigenesis and progression of epithelial ovarian carcinoma by regulating activity of ATG3.
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lncRNA Meg3上调诱导自噬通过调节ATG3活性抑制上皮性卵巢癌的发生和进展
DOI：
10.18632/oncotarget.15955
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发表时间：
2017-05-09
期刊：
影响因子：
--
通讯作者：
Zong ZH
中科院分区：
文献类型：
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作者：
Xiu YL;Sun KX;Chen X;Chen S;Zhao Y;Guo QG;Zong ZH
母系表达基因3（Meg 3）是一种长链非编码RNA，与多种恶性肿瘤的发生有关。然而，关于Meg 3在上皮性卵巢癌（EOC）中的作用知之甚少。在本研究中，我们发现Meg 3在上皮性卵巢癌中的表达较低，有可能被认为是卵巢癌的生物标志物。用Meg 3转染卵巢癌细胞系OVCAR 3和A2780后，检测表型变化和自噬相关分子。Meg 3的上调抑制细胞增殖，平板集落形成，诱导细胞周期停滞在G2期，并促进凋亡。透射电子显微镜观察自噬体。LC 3-II、ATG 3、LAMP 1的表达水平升高，而SQSTM 1/p62的表达水平下降。Meg 3的上调表达还通过上调ATG 3表达在异种移植小鼠模型中抑制体内肿瘤发生。RIP（核糖核蛋白免疫沉淀）和RNA下拉试验表明，Meg 3与ATG 3免疫共沉淀。此外，Meg 3保护ATG 3 mRNA免受放线菌素D处理后的降解。总之，我们的研究结果表明，lncRNA Meg 3作为一个肿瘤抑制剂在EOC中通过调节ATG 3活性和诱导自噬。
Maternally expressed gene 3 (Meg3), a long non-coding RNA, has been reported to be associated with the pathogenesis of multiple malignancies. However, little is known regarding the role of Meg3 in epithelial ovarian cancer (EOC). In this study, we found that the expression of Meg3 was lower in epithelial ovarian carcinoma, and has potential to be considered as a biomarker for ovarian cancer. After transfecting the ovarian cancer cell lines OVCAR3 and A2780 with Meg3, phenotypic changes and autophagy-related molecules were examined. Upregulation of Meg3 inhibited cell proliferation, plate colony formation, induced cell cycle arrest in G2 phases, and promoted apoptosis. Observation of autophagosomes was performed by transmission electron microscopy. The expression levels of LC3-II, ATG3, LAMP1 were elevated, while SQSTM1/p62 expression declined. Upregulated expression of Meg3 also suppressed tumorigenesis in vivo in a xenograft mouse model through upregulating ATG3 expression. RIP (ribonucleoprotein immunoprecipitation) and RNA pull-down assays showed that Meg3 was co-immunoprecipitated with ATG3. In addition, Meg3 protected ATG3 mRNA from degradation following treatment with actinomycin D. Overall, our results suggest that the lncRNA Meg3 acts as a tumor suppressor in EOC by regulating ATG3 activity and inducing autophagy.