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AGAP2-AS1/miR-628-5p/FOXP2 feedback loop facilitates the growth of prostate cancer via activating WNT pathway.
Carcinogenesis ( IF 4.7 ) Pub Date : 2021-10-26 , DOI: 10.1093/carcin/bgab062
Xu Zhao 1, 2 , Yajun Liu 3 , Chenggong Luo 2, 4 , Yali Zuo 1
Affiliation  

Increasing studies have indicated the critical roles of long non-coding RNAs (lncRNAs) in the tumorigenesis of cancers. LncRNA AGAP2 antisense RNA 1 (AGAP2-AS1) can serve as an oncogenic role in some cancers, including prostate cancer (PCa). However, the underling mechanism of such lncRNA in PCa has not been fully studied. Therefore, it is meaningful to investigate the role and underlying mechanism of AGAP2-AS1 in PCa. AGAP2-AS1 was confirmed to be highly expressed in PCa cells. Functionally, AGAP2-AS1 silencing inhibited cell proliferation, migration, invasion and epithelial-mesenchymal transition process and induced apoptosis. According to mechanism assays, AGAP2-AS1 sponged miR-628-5p, which was found to restrain PCa cell growth. Besides, FOXP2 was identified as a target gene of miR-628-5p, and its expression was negatively regulated by miR-628-5p and positively modulated by AGAP2-AS1. Importantly, we found that FOXP2 could function as the upstream gene of AGAP2-AS1. Through rescue experiments, we discovered that FOXP2 up-regulation countered AGAP2-AS1 knockdown-mediated inhibition on PCa cell growth. Finally, it was found that AGAP2-AS1 could activate WNT pathway, and LiCl could reverse the influence of AGAP2-AS1 on PCa biological behaviors. To conclude, AGAP2-AS1/miR-628-5p/FOXP2 feedback loop facilitated PCa cell growth via activating WNT pathway.

中文翻译:

AGAP2-AS1/miR-628-5p/FOXP2 反馈环通过激活 WNT 通路促进前列腺癌的生长。

越来越多的研究表明长链非编码 RNA (lncRNA) 在癌症的肿瘤发生中的关键作用。LncRNA AGAP2 反义 RNA 1 (AGAP2-AS1) 可在某些癌症中发挥致癌作用,包括前列腺癌 (PCa)。然而,此类 lncRNA 在 PCa 中的潜在机制尚未得到充分研究。因此,研究AGAP2-AS1在PCa中的作用及其潜在机制具有重要意义。确认 AGAP2-AS1 在 PCa 细胞中高表达。在功能上,AGAP2-AS1 沉默抑制细胞增殖、迁移、侵袭和上皮-间质转化过程并诱导细胞凋亡。根据机制分析,AGAP2-AS1 海绵化 miR-628-5p,发现其抑制 PCa 细胞生长。此外,FOXP2 被鉴定为 miR-628-5p 的靶基因,其表达受 miR-628-5p 负调控,受 AGAP2-AS1 正调控。重要的是,我们发现 FOXP2 可以作为 AGAP2-AS1 的上游基因。通过救援实验,我们发现 FOXP2 上调抵消了 AGAP2-AS1 敲低介导的对 PCa 细胞生长的抑制。最后发现AGAP2-AS1可以激活WNT通路,LiCl可以逆转AGAP2-AS1对PCa生物学行为的影响。总之,AGAP2-AS1/miR-628-5p/FOXP2 反馈环通过激活 WNT 通路促进 PCa 细胞生长。发现AGAP2-AS1可以激活WNT通路,LiCl可以逆转AGAP2-AS1对PCa生物学行为的影响。总之,AGAP2-AS1/miR-628-5p/FOXP2 反馈环通过激活 WNT 通路促进 PCa 细胞生长。发现AGAP2-AS1可以激活WNT通路,LiCl可以逆转AGAP2-AS1对PCa生物学行为的影响。总之,AGAP2-AS1/miR-628-5p/FOXP2 反馈环通过激活 WNT 通路促进 PCa 细胞生长。
更新日期:2021-07-13
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