Ma Xiulong, Wang Zhongwei, Ren Hongtao, Bao Xing, Zhang Yang, Wang Baofeng, Ruan Dongli
Department of Radiation Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China.
Department of Urology, Xijing Hospital, Air Force Military Medical University, Xi'an, Shaanxi 710032, People's Republic of China.
Cancer Manag Res. 2020 Sep 22;12:8833-8845. doi: 10.2147/CMAR.S244123. eCollection 2020.
Long non-coding RNAs (lncRNAs) function as a class of significant mediators in prostate cancer (PCa), and this study mainly discussed the molecular mechanism of lncRNA growth arrest-specific 5 (GAS5) in PCa progression and radiosensitivity.
GAS5 and microRNA-320a (miR-320a) levels were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability and migration were severally examined through 3-(4, 5-dimethylthiazol-2-y1)-2, 5-diphenyl tetrazolium bromide (MTT) and transwell assays. PCa cells were treated with X-ray irradiation. Cell survival and apoptosis rate were assayed using colony formation assay and flow cytometry, respectively. The apoptosis-related protein and Rab GTPase 21 () protein levels were measured by Western blot. The relation between miR-320a and GAS5 or was assessed via the dual-luciferase reporter assay. The effect of GAS5 on radiosensitivity of PCa in vivo was evaluated by xenotransplantation assay.
GAS5 was down-regulated in PCa tissues and cells. GAS5 overexpression suppressed cell viability and migration while facilitated radiosensitivity of PCa cells. GAS5 was a molecular sponge of miR-320a. The effects of GAS5 up-regulation on PCa cells were accomplished by sponging miR-320a. MiR-320a targeted and GAS5 up-regulated expression via targeting miR-320a. knockdown reversed the effects of miR-320a inhibition on PCa cells. GAS5 promoted the radiosensitivity of PCa by the miR-320a/ axis in vivo.
Collectively, GAS5 restrained tumor development and expedited the radiosensitivity in PCa by the miR-320a/ axis, which provided a molecular regulatory mechanism of GAS5/miR-320a/ in PCa development and radioresistance.
长链非编码RNA（lncRNAs）在前列腺癌（PCa）中作为一类重要的调节因子发挥作用，本研究主要探讨lncRNA生长停滞特异性5（GAS5）在PCa进展和放射敏感性中的分子机制。
通过定量实时聚合酶链反应（qRT-PCR）测定GAS5和微小RNA-320a（miR-320a）水平。分别通过3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）和Transwell实验检测细胞活力和迁移能力。对PCa细胞进行X射线照射处理。分别使用集落形成实验和流式细胞术检测细胞存活率和凋亡率。通过蛋白质免疫印迹法检测凋亡相关蛋白和Rab GTPase 21（）蛋白水平。通过双荧光素酶报告基因实验评估miR-320a与GAS5或之间的关系。通过异种移植实验评估GAS5对PCa体内放射敏感性的影响。
GAS5在PCa组织和细胞中表达下调。GAS5过表达抑制细胞活力和迁移，同时提高PCa细胞的放射敏感性。GAS5是miR-320a的分子海绵。上调GAS5对PCa细胞的影响是通过吸附miR-320a实现的。miR-320a靶向，GAS5通过靶向miR-320a上调表达。敲低可逆转抑制miR-320a对PCa细胞的影响。在体内，GAS5通过miR-320a/轴促进PCa的放射敏感性。
总体而言，GAS5通过miR-320a/轴抑制PCa肿瘤发展并提高其放射敏感性，这为GAS5/miR-320a/在PCa发展和放射抗性中的分子调控机制提供了依据。
