Chen Changxuan, Wang Kaizhen, Wang Qian, Wang Xin
Tengzhou Central People's Hospital, Department of Urology, Jining Medical College, Tengzhou, China.
Tengzhou Central People's Hospital, Department of Traumatology, Jining Medical College, Tengzhou, China.
Braz J Med Biol Res. 2018;51(6):e7080. doi: 10.1590/1414-431x20187080. Epub 2018 Apr 23.
Prostate cancer (PCa) is the second leading cause of cancer death in men. Irradiation is one of the available options for treatment of PCa, however, approximately 10-45% of PCa are resistant to irradiation. We aimed to explore the role of long non-coding RNA highly upregulated in liver cancer (HULC) in the sensitivity of PCa cells to irradiation. Survival rate, cell apoptosis, cycle, expressions of related proteins, and caspase-3 activity were assessed to explore the effects of HULC on sensitivity of PCa cells to irradiation. Expression of HULC in DU-145, PC3, LNCaP, and RWPE-1 cells was determined and the influence of HULC on DU-145 cells was explored. Then, PC3 cells aberrantly expressing HULC were implanted into NOD-SCID mice for tumor xenograft study. Changes of autophagy after aberrant expression of HULC in vivo and in vitro were tested. Furthermore, the interacted protein of HULC and involved signaling pathway were investigated. In PC3 and LNCaP cells under irradiation, survival rate and cell cycle were decreased and apoptosis was increased by HULC knockdown. HULC knockdown arrested PC3 cells at G0/G1 phase. DU-145 was sensitive to irradiation, and resistance to irradiation of DU-145 cells was enhanced by HULC overexpression. Moreover, HULC knockdown enhanced the sensitivity of PC3 xenografts to irradiation. HULC knockdown promoted autophagy through interaction with Beclin-1 and inhibition of mTOR, resulting in increased apoptosis. HULC knockdown improved sensitivity of PCa cells to irradiation both in vivo and in vitro. HULC suppressed Beclin-1 phosphorylation, thereby reduced autophagy, involving the mTOR pathway.
前列腺癌（PCa）是男性癌症死亡的第二大主要原因。放射治疗是PCa的可用治疗选择之一，然而，约10 - 45%的PCa对放射治疗具有抗性。我们旨在探讨肝癌中高度上调的长链非编码RNA（HULC）在PCa细胞对放射治疗敏感性中的作用。评估存活率、细胞凋亡、细胞周期、相关蛋白表达和半胱天冬酶-3活性，以探讨HULC对PCa细胞放射治疗敏感性的影响。测定HULC在DU-145、PC3、LNCaP和RWPE-1细胞中的表达，并探讨HULC对DU-145细胞的影响。然后，将异常表达HULC的PC3细胞植入NOD-SCID小鼠进行肿瘤异种移植研究。检测HULC在体内和体外异常表达后的自噬变化。此外，研究了HULC的相互作用蛋白和涉及的信号通路。在照射条件下，PC3和LNCaP细胞中，HULC敲低可降低存活率和细胞周期，增加细胞凋亡。HULC敲低使PC3细胞停滞在G0/G1期。DU-145对放射治疗敏感，HULC过表达增强了DU-145细胞对放射治疗的抗性。此外，HULC敲低增强了PC3异种移植瘤对放射治疗的敏感性。HULC敲低通过与Beclin-1相互作用并抑制mTOR促进自噬，导致细胞凋亡增加。HULC敲低在体内和体外均提高了PCa细胞对放射治疗的敏感性。HULC抑制Beclin-1磷酸化，从而减少自噬，涉及mTOR通路。
