Long noncoding RNA DNAH17-AS1 promotes tumorigenesis and metastasis of non-small cell lung cancer via regulating miR-877-5p/CCNA2 pathway
Long noncoding RNA DNAH17-AS1 promotes tumorigenesis and metastasis of non-small cell lung cancer via regulating miR-877-5p/CCNA2 pathway
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DOI：
10.1016/j.bbrc.2020.09.047
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发表时间：
2020-12-10
影响因子：
3.1
通讯作者：
Jing, Rui-jun
中科院分区：
文献类型：
--
作者：
Du, Li-juan;Mao, Long-jun;Jing, Rui-jun
越来越多的研究表明，长链非编码RNA（lncRNA）可以作为重要的癌基因或肿瘤抑制因子发挥作用。本研究旨在探讨lncRNA DNAH 17反义RNA 1（DNAH 17-AS 1）对非小细胞肺癌（NSCLC）的调控作用及其分子机制。我们观察到DNAH 17-AS 1和CCNA 2 mRNA在NSCLC标本和细胞系中的表达明显上调，而miR-877- 5 p的表达显著降低。DNAH 17-AS 1可用于区分NSCLC标本与邻近非肿瘤组织。临床分析表明，高DNAH 17-AS 1与TNM分期、远处转移、总生存期和无病生存期缩短有关。功能分析表明，敲低DNAH 17-AS 1基因可抑制H1299和95 D细胞的增殖、迁移和侵袭，并促进细胞凋亡。在机械上，DNAH 17-AS 1充当miR-877- 5 p的竞争性内源RNA（ceRNA）以正回收CCNA 2。总之，我们鉴定了一种新的NSCLC相关lncRNA，DNAH 17-AS 1，其可以通过充当miR-877- 5 p的海绵来上调CCNA 2而发挥致癌功能。我们的研究为NSCLC进展提供了新的见解，并为NSCLC提供了前瞻性的治疗靶点。(C)2020爱思唯尔公司All rights reserved.
A growing number of studies have revealed that long noncoding RNAs (lncRNAs) can function as important oncogenes or tumor suppressors. This study aimed to investigate the regulatory role of lncRNA DNAH17 antisense RNA 1 (DNAH17-AS1) on non-small cell lung cancer (NSCLC) and the underlying molecular mechanisms. We observed that the expression of DNAH17-AS1 and CCNA2 mRNA was distinctly upregulated in NSCLC specimens and cell lines, while miR-877-5p expression was significantly decreased. DNAH17-AS1 could be used to distinguish NSCLC specimens from adjacent non-tumor tissues. Clinical assays revealed that high DNAH17-AS1 was associated with TNM stage, distant metastasis and shorter overall survival and disease-free survival. Functional assays indicated that knockdown of DNAH17-AS1 suppressed the proliferation, migration and invasion of H1299 and 95D cells, and promoted apoptosis. Mechanically, DNAH17-AS1 served as competing endogenous RNA (ceRNA) for miR-877-5p to positively recover CCNA2. Overall, we identified a novel NSCLC-related lncRNA, DNAH17-AS1 which may exert an oncogenic function via serving as a sponge for miR-877-5p to upregulate CCNA2. Our study presents novel insights into NSCLC progression and provided a prospective therapeutic target for NSCLC. (C) 2020 Elsevier Inc. All rights reserved.