Department of Breast Surgery, Henan Provincial People's Hospital/People's Hospital of Zhengzhou University, Zhengzhou, Henan 450003, P.R. China.
Oncol Rep. 2020 Oct;44(4):1511-1523. doi: 10.3892/or.2020.7699. Epub 2020 Jul 20.
The high metastatic rate of breast cancer is the significant cause of its poor prognosis. The long noncoding RNA (lncRNA) proliferating cell nuclear antigen pseudogene 1 (PCNAP1) plays important roles in the initiation and progression of cancers; however, its regulatory function and molecular mechanism in breast cancer metastasis remains unknown. Therefore, we investigated the roles of lncRNA PCNAP1 in breast cancer metastasis by modulating the microRNA (miR)‑340‑5p/SOX4 axis using quantitative real‑time PCR, in vivo mouse models, nucleo‑cytoplasmic separation, western blot analysis, scratch assays, Transwell assays, luciferase reporter assays and MS2‑RIP, in vitro and in vivo. lncRNA PCNAP1 was found to be upregulated in human breast cancer tissues, and high lncRNA PCNAP1 levels predicted poor overall survival. Function assays showed that knockdown of lncRNA PCNAP1 suppressed the migration and invasion of breast cancer cells in vitro and in vivo. Mechanistically, lncRNA PCNAP1 functioned as a competing endogenous (ce)RNA for miR‑340‑5p to facilitate the expression of its target gene SRY‑box transcription factor 4 (SOX4), promoting migration and invasion of breast cancer cells. Overall, we found that lncRNA PCNAP1 predicted a poor prognosis in breast cancer and promoted cancer metastasis via miR‑340‑5p‑dependent upregulation of SOX4 expression. These results suggest that lncRNA PCNAP1 has potential as an alternative therapeutic target to suppress breast cancer metastasis.
乳腺癌的高转移率是其预后不良的重要原因。长链非编码 RNA（lncRNA）增殖细胞核抗原假基因 1（PCNAP1）在癌症的发生和发展中发挥重要作用；然而，其在乳腺癌转移中的调控功能和分子机制尚不清楚。因此，我们通过调节 microRNA（miR）-340-5p/ SOX4 轴，使用定量实时 PCR、体内小鼠模型、核质分离、western blot 分析、划痕实验、Transwell 实验、荧光素酶报告实验和 MS2-RIP，研究了 lncRNA PCNAP1 在乳腺癌转移中的作用，在体外和体内。发现 lncRNA PCNAP1 在人乳腺癌组织中上调，高 lncRNA PCNAP1 水平预示着总体生存率差。功能测定表明，lncRNA PCNAP1 的敲低抑制了乳腺癌细胞在体外和体内的迁移和侵袭。机制上，lncRNA PCNAP1 作为 miR-340-5p 的竞争性内源性（ce）RNA 发挥作用，促进其靶基因 SRY-盒转录因子 4（SOX4）的表达，从而促进乳腺癌细胞的迁移和侵袭。总的来说，我们发现 lncRNA PCNAP1 预测乳腺癌预后不良，并通过 miR-340-5p 依赖性上调 SOX4 表达促进癌症转移。这些结果表明，lncRNA PCNAP1 具有作为抑制乳腺癌转移的替代治疗靶点的潜力。
