Sun Baolan, Xia Zhengting, Cai Fuying, Wang Pengbo, Xu Meiyu, Wu Youjia
Department of Pediatrics, Affiliated Hospital of Nantong University.
Department of Pediatrics, People's Hospital of Yangzhong City, Yangzhong, The People's Republic of China.
J Pediatr Hematol Oncol. 2018 Nov;40(8):588-593. doi: 10.1097/MPH.0000000000001198.
Our previous work showed that a proliferation-inducing ligand (APRIL) was involved in the development of acute lymphoblastic leukemia (ALL) in children. However, the precise role of APRIL in ALL remains unknown. To investigate this issue, we silenced and overexpressed APRIL in Nalm-6 ALL cells using short hairpin RNA targeting the APRIL gene and recombinant human APRIL, respectively, and evaluated the effects on cell proliferation, apoptosis, and migration. APRIL mRNA and APRIL and matrix metalloproteinase-2 protein levels were evaluated by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) and western blott, respectively. We found that APRIL expression was reduced by shRNA-mediated knockdown in Nalm-6 cells; this was associated with a decrease in cell proliferation (P<0.05). APRIL knockdown increased apoptosis (P<0.01) but suppressed cell migration along with matrix metalloproteinase-2 protein level. Overexpressing recombinant human APRIL had the opposite effects in each case (P<0.05). These results demonstrate a link between APRIL expression and ALL development and suggest that APRIL is a potential therapeutic target for ALL treatment.
我们之前的研究表明，增殖诱导配体（APRIL）参与儿童急性淋巴细胞白血病（ALL）的发展。然而，APRIL在ALL中的具体作用仍不清楚。为了研究这个问题，我们分别使用靶向APRIL基因的短发夹RNA和重组人APRIL，在Nalm-6 ALL细胞中沉默和过表达APRIL，并评估其对细胞增殖、凋亡和迁移的影响。分别通过半定量逆转录-聚合酶链反应（RT-PCR）和蛋白质印迹法评估APRIL mRNA以及APRIL和基质金属蛋白酶-2蛋白水平。我们发现，shRNA介导的Nalm-6细胞中APRIL表达降低；这与细胞增殖减少相关（P<0.05）。APRIL敲低增加了细胞凋亡（P<0.01），但抑制了细胞迁移以及基质金属蛋白酶-2蛋白水平。在每种情况下，过表达重组人APRIL都产生相反的效果（P<0.05）。这些结果证明了APRIL表达与ALL发展之间的联系，并表明APRIL是ALL治疗的潜在靶点。
