Zhang Wenyuan, Liu Qionghong, Zhao Jun, Wang Tiejun, Wang Jinshan
Department of Urology, East Hospital, Ji'an Hospital, Jiangxi, 343000, People's Republic of China.
Department of Urology, East Hospital, Tongji University School of Medicine, Shanghai, 200123, People's Republic of China.
Cancer Manag Res. 2021 Jun 28;13:5091-5100. doi: 10.2147/CMAR.S310529. eCollection 2021.
Long noncoding RNAs (lncRANs) as suppressive or oncogenic genes have been substantiated in prostate cancer (PCa). In the current study, the role and molecular mechanism of lncRNA AATBC in the progression of PCa was evaluated.
LncRNA AATBC and miR-1245b-5p expression were evaluated using RT-qPCR. CCK-8, colony-formation, apoptosis and transwell assay were used to analyze the in vitro role. The xenograft model was used to explore the in vivo role. Bioinformatics analysis and a dual luciferase assay, RIP and RNA pull down were used to confirm the interaction between lncRNA AATBC and 1245b-5p, as well as 1245b-5p and CASK.
Firstly, we certified that the expression of AATBC was augmented in PCa, and knockdown of AATBC could significantly inhibit the growth of PCa in vitro and in vivo. Mechanistically, our results manifested that AATBC could directly bind to miR-1245b-5p. In addition, miR-1245b-5p played cancer-suppressive role in PCa cells. Moreover, CASK was attested as the target of miR-1245b-5p, and CASK was demonstrated to exert as oncogene in the progression of PCa. Finally, rescue assays illustrated that miR-1245b-5p downregulation or CASK restoration could greatly resist the restrained effects of AATBC knockdown on PCa progression.
AATBC could accelerate the progression of PCa through regulating miR-1245b-5p/CASK axis, which provided a potential therapeutic target for PCa treatment.
长链非编码RNA(lncRNA)作为抑癌或致癌基因在前列腺癌(PCa)中已得到证实。在本研究中,评估了lncRNA AATBC在PCa进展中的作用及分子机制。
采用RT-qPCR评估lncRNA AATBC和miR-1245b-5p的表达。使用CCK-8、集落形成、凋亡和Transwell实验分析其体外作用。采用异种移植模型探索其体内作用。通过生物信息学分析、双荧光素酶实验、RNA免疫沉淀(RIP)和RNA下拉实验证实lncRNA AATBC与1245b-5p之间的相互作用,以及1245b-5p与钙/钙调蛋白依赖性丝氨酸蛋白激酶(CASK)之间的相互作用。
首先,我们证实AATBC在PCa中表达上调,敲低AATBC可显著抑制PCa在体外和体内的生长。机制上,我们的结果表明AATBC可直接与miR-1245b-5p结合。此外,miR-1245b-5p在PCa细胞中发挥抑癌作用。而且,CASK被证实为miR-1245b-5p的靶标,并且CASK在PCa进展中被证明发挥癌基因作用。最后,挽救实验表明miR-1245b-5p下调或CASK恢复可极大地抵抗AATBC敲低对PCa进展的抑制作用。
AATBC可通过调节miR-1245b-5p/CASK轴加速PCa的进展,这为PCa治疗提供了一个潜在的治疗靶点。