Long Noncoding RNA FAM225A Promotes Nasopharyngeal Carcinoma Tumorigenesis and Metastasis by Acting as ceRNA to Sponge miR-590-3p/miR-1275 and Upregulate ITGB3
Long Noncoding RNA FAM225A Promotes Nasopharyngeal Carcinoma Tumorigenesis and Metastasis by Acting as ceRNA to Sponge miR-590-3p/miR-1275 and Upregulate ITGB3
复制标题
长非编码RNA FAM225A通过作为ceRNA海绵miR-590-3p/miR-1275并上调ITGB3促进鼻咽癌肿瘤发生和转移
DOI：
10.1158/0008-5472.can-19-0799
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发表时间：
2019-09-15
期刊：
影响因子：
11.2
通讯作者：
Sun, Ying
中科院分区：
文献类型：
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作者：
Zheng, Zi-Qi;Li, Zhi-Xuan;Sun, Ying
长链非编码RNA（lncRNA）在肿瘤的发生和发展中起重要作用。然而，lncRNA的临床意义及其在鼻咽癌（NPC）发生中的调控机制在很大程度上是未知的。在此，基于微阵列分析，我们鉴定了384个失调的lncRNA，其中，FAM 225 A是NPC中上调最多的lncRNA之一。FAM 225 A与NPC的生存率显著相关。N（6）-甲基腺苷（m6 A）在FAM 225 A中高度富集并增强其RNA稳定性。FAM 225 A作为一种致癌lncRNA，促进NPC细胞增殖、迁移、侵袭、肿瘤生长和转移。FAM 225 A作为竞争性内源性RNA（ceRNA）作用于miR-590- 3 p和miR-1275，导致其靶整合素β 3（ITGB 3）上调，并激活FAK/PI 3 K/Akt信号传导，从而促进NPC细胞增殖和侵袭。总之，我们的研究揭示了一个潜在的ceRNA调控途径，其中FAM 225 A通过与miR-590- 3 p和miR-1275结合来调节ITGB 3的表达，最终促进NPC的肿瘤发生和转移。这些发现证实了lncRNA FAM 225 A在鼻咽癌（NPC）中的临床意义以及参与NPC发展和进展的调控机制，提供新的预后指标和有希望的治疗靶点。
Long noncoding RNAs (lncRNA) play important roles in the tumorigenesis and progression of cancers. However, the clinical significance of lncRNAs and their regulatory mechanisms in nasopharyngeal carcinogenesis (NPC) are largely unknown. Here, based on a microarray analysis, we identified 384 dysregulated lncRNAs, of which, FAM225A was one of the most upregulated lncRNAs in NPC. FAM225A significantly associated with poor survival in NPC. N(6)-Methyladenosine (m6A) was highly enriched within FAM225A and enhanced its RNA stability. FAM225A functioned as an oncogenic lncRNA that promoted NPC cell proliferation, migration, invasion, tumor growth, and metastasis. Mechanistically, FAM225A functioned as a competing endogenous RNA (ceRNA) for sponging miR-590-3p and miR-1275, leading to the upregulation of their target integrin beta 3 (ITGB3), and the activation of FAK/PI3K/Akt signaling to promote NP Ccell proliferation and invasion. In summary, our study reveals a potential ceRNA regulatory pathway in which FAM225A modulates ITGB3 expression by binding to miR-590-3p and miR-1275, ultimately promoting tumorigenesis and metastasis in NPC.Significance: These findings demonstrate the clinical significance of the lncRNA FAM225A in nasopharyngeal carcinoma (NPC) and the regulatory mechanism involved in NPC development and progression, providing a novel prognostic indicator and promising therapeutic target.