长链非编码 RNA FOXP4-AS1 受 PAX5 激活，并通过与 miR-3184-5p 结合来上调 FOXP4，从而促进前列腺癌的生长。

LncRNA FOXP4-AS1 is activated by PAX5 and promotes the growth of prostate cancer by sequestering miR-3184-5p to upregulate FOXP4.

机构信息

Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.

Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.

出版信息

Cell Death Dis. 2019 Jun 17;10(7):472. doi: 10.1038/s41419-019-1699-6.

Prostate cancer (PCa) is one of the major men malignancies worldwide. Long noncoding RNAs (lncRNAs) have been reported as essential regulators in human cancers, including PCa. In the present study, lncRNA forkhead box P4 antisense RNA 1 (FOXP4-AS1) was found to be highly expressed in TCGA PCa samples. Upregulation of FOXP4-AS1 was further validated in 64 PCa tissues and predicted poor prognosis in patients with PCa. Functionally, high FOXP4-AS1 level was associated with increased cell proliferation and decreased cell apoptosis, indicating that FOXP4-AS1 exerted oncogenic functions in the tumorigenesis of PCa. Furthermore, FOXP4-AS1 was located in the cytoplasm of PCa cell lines and positively regulated FOXP4. LncRNAs can exert their functions by cooperating with their nearby genes. Mechanistically, FOXP4-AS1 post-transcriptionally regulated FOXP4 by acting as a competing endogenous RNA (ceRNA) in PCa to sponge miR-3184-5p. Considering the upregulation of both FOXP4-AS1 and its nearby gene FOXP4, we further detected the coactivator of FOXP4-AS1 and FOXP4. Mechanism analysis indicated that paired box 5 (PAX5) transcriptionally activated FOXP4-AS1 and FOXP4 in PCa. Collectively, we determined that PAX5-induced upregulation of FOXP4-AS1/FOXP4 axis promoted tumorigenesis of PCa.

前列腺癌（PCa）是全球男性主要的恶性肿瘤之一。长链非编码 RNA（lncRNA）已被报道为包括 PCa 在内的人类癌症的重要调控因子。在本研究中，发现叉头框蛋白 P4 反义 RNA 1（FOXP4-AS1）在 TCGA PCa 样本中高度表达。FOXP4-AS1 的上调在 64 例 PCa 组织中得到进一步验证，并预测 PCa 患者预后不良。功能上，高 FOXP4-AS1 水平与细胞增殖增加和细胞凋亡减少有关，表明 FOXP4-AS1 在 PCa 的肿瘤发生中发挥致癌作用。此外，FOXP4-AS1 位于 PCa 细胞系的细胞质中，并正向调节 FOXP4。lncRNA 可以通过与附近基因合作发挥其功能。从机制上讲，FOXP4-AS1 通过作为 PCa 中的竞争性内源 RNA（ceRNA）来反式调节 FOXP4。考虑到 FOXP4-AS1 和其附近基因 FOXP4 的上调，我们进一步检测了 FOXP4-AS1 和 FOXP4 的共激活子。机制分析表明，配对盒 5（PAX5）在 PCa 中转录激活 FOXP4-AS1 和 FOXP4。综上所述，我们确定 PAX5 诱导的 FOXP4-AS1/FOXP4 轴的上调促进了 PCa 的肿瘤发生。