PYCR1 在 miR-488 的负调控下促进非小细胞肺癌的进展。
PYCR1 promotes the progression of non-small-cell lung cancer under the negative regulation of miR-488.
机构信息
Department of Respiration, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
Department of Respiration, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
出版信息
Biomed Pharmacother. 2019 Mar;111:588-595. doi: 10.1016/j.biopha.2018.12.089. Epub 2018 Dec 31.
PYCR1 is over-expressed in non-small-cell lung cancer (NSCLC) and its high expression accelerates the progression of NSCLC. However, the underlying mechanisms of PYCR1 in NSCLC progression remain poorly understood. Our study determined the mechanisms of PYCR1 in promotion of the occurrence and development of NSCLC in vitro and in vivo. Firstly, the expression patterns of PYCR1 in NSCLC tissues and cells were determined by RT-PCR, western blot and immunohistochemistry. Then, the effects of PYCR1 on cell proliferation and apoptosis were evaluated by CCK-8 and flow cytomery assays. Finally, we explored the up-regulatory microRNAs (miRs) of PYCR1 and determined if MAPK pathway involved in this process. PYCR1 expression was elevated in NSCLC tissue samples and cells, and the high expression of PYCR1 closely associated with patients' advanced clinical process and poor outcome. Up-regulation of PYCR1 significantly increased the expression of p38 and promoted its nuclear accumulation. Besides, PYCR1 expression was negatively regulated by miR-488, and up-regulation of miR-488 significantly inhibited cell proliferation and tumorigenesis and increased cell apoptosis, and decreased p38 expression and its nuclear accumulation, whereas up-regulation of PYCR1 rescued these results induced by miR-488 over-expression. Collectively, these data suggest the mechanism of PYCR1 in promotion of NSCLC progression. PYCR1 is negatively regulated by miR-488 and then promotes the occurrence and development of NSCLC and activates p38 MAPK pathway.
PYCR1 在非小细胞肺癌（NSCLC）中过表达，其高表达加速了 NSCLC 的进展。然而，PYCR1 在 NSCLC 进展中的潜在机制仍知之甚少。我们的研究确定了 PYCR1 在体外和体内促进 NSCLC 发生和发展的机制。首先，通过 RT-PCR、western blot 和免疫组织化学测定 NSCLC 组织和细胞中 PYCR1 的表达模式。然后，通过 CCK-8 和流式细胞术测定评估 PYCR1 对细胞增殖和凋亡的影响。最后，我们探讨了 PYCR1 的上调 microRNAs（miRs），并确定 MAPK 通路是否参与了这一过程。PYCR1 在 NSCLC 组织样本和细胞中的表达上调，并且 PYCR1 的高表达与患者的晚期临床过程和不良预后密切相关。PYCR1 的上调显著增加了 p38 的表达，并促进其核积累。此外，PYCR1 的表达受 miR-488 的负调控，miR-488 的上调显著抑制细胞增殖和肿瘤发生，增加细胞凋亡，并降低 p38 的表达及其核积累，而 PYCR1 的上调则挽救了由 miR-488 过表达引起的这些结果。总之，这些数据表明了 PYCR1 在促进 NSCLC 进展中的作用机制。PYCR1 受 miR-488 的负调控，从而促进 NSCLC 的发生和发展，并激活 p38 MAPK 通路。
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