Long non‑coding RNA FEZF1‑AS1 facilitates non‑small cell lung cancer progression via the ITGA11/miR‑516b‑5p axis.
Long non‑coding RNA FEZF1‑AS1 facilitates non‑small cell lung cancer progression via the ITGA11/miR‑516b‑5p axis.
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DOI：
10.3892/ijo.2020.5142
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发表时间：
2020-12
影响因子：
5.2
通讯作者：
Xing L
中科院分区：
文献类型：
--
作者：
Song H;Li H;Ding X;Li M;Shen H;Li Y;Zhang X;Xing L
长非编码RNA(LncRNAs)已成为癌症发生发展过程中的关键分子。FEZ家族锌指1反义RNA1(FEZF1-AS1)是一种新的参与肿瘤发生发展的转录因子RNA，是一种潜在的肿瘤生物标志物。然而，FEZF1-AS1在非小细胞肺癌(NSCLC)中的临床意义和分子机制尚不清楚。在本研究中，利用Arraystar Human LncRNA微阵列筛选FEZF1-AS1基因，发现FEZF1-AS1基因在NSCLC组织中表达上调，并与NSCLC患者的总生存期呈负相关。功能丧失分析显示，抑制FEZF1-AS1使细胞增殖和迁移减少，并使细胞停滞在G2/M期。在机制上，N6-甲基腺苷(M6A)修饰影响FEZF1-AS1的表达。由于FEZF1-AS1主要定位于非小细胞肺癌细胞的胞浆部分，推测其可能参与竞争的内源性RNA调控网络，从而影响非小细胞肺癌的预后。通过整合Arraystar人基因芯片数据和miRNA生物信息学分析，发现ITGA11的表达随着FEZF1-AS1的缺失而降低，随着FEZF1-AS1的表达增强而增加，并且microRNA(MiR)-516b-5p抑制FEZF1-AS和ITGA11的表达水平。RNA结合蛋白免疫沉淀和RNA下拉实验进一步证明FEZF1-AS1能与miR-516b-5p结合，荧光素酶报告基因分析表明ITGA11是miR-516b-5p的直接靶点。总之，本研究结果表明FEZF1-AS1通过调节ITGA11/miR-516b-5p轴在非小细胞肺癌中表达上调并发挥癌基因的作用，提示FEZF1-AS1可能是NSCLC一个潜在的预后生物标志物和治疗靶点。
Long non-coding RNAs (lncRNAs) have emerged as key players in the development and progression of cancer. FEZ family zinc finger 1 antisense RNA 1 (FEZF1-AS1) is a novel lncRNA that is involved in the development of cancer and acts as a potential biomarker for cancer. However, the clinical significance and molecular mechanism of FEZF1-AS1 in non-small cell lung cancer (NSCLC) remains uncertain. In the present study, FEZF1-AS1 was selected using Arraystar Human lncRNA microarray and was identified to be upregulated in NSCLC tissues and negatively associated with the overall survival of patients with NSCLC. Loss-of-function assays revealed that FEZF1-AS1 inhibition decreased cell proliferation and migration, and arrested cells at the G2/M cell cycle phase. Mechanistically, FEZF1-AS1 expression was influenced by N6-methyladenosine (m6A) modification. Since FEZF1-AS1 was mainly located in the cytoplasmic fraction of NSCLC cells, it was hypothesized that it may be involved in competing endogenous RNA regulatory network to impact the prognosis of NSCLC. Via integrating Arraystar Human mRNA microarray data and miRNA bioinformatics analysis, it was revealed that ITGA11 expression was decreased with loss of FEZF1-AS1 and increased with gain of FEZF1-AS1 expression, and microRNA (miR)-516b-5p inhibited the expression levels of both FEZF1-AS and ITGA11. RNA-binding protein immunoprecipitation and RNA pulldown assays further demonstrated that FEZF1-AS1 could bind to miR-516b-5p and that ITGA11 was a direct target of miR-516b-5p by luciferase reporter assay. Overall, the present findings demonstrated that FEZF1-AS1 was upregulated and acted as an oncogene in NSCLC by regulating the ITGA11/miR-516b-5p axis, suggesting that FEZF1-AS1 may be a potential prognostic biomarker and therapeutic target for NSCLC.
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影响因子：
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