Aksoy Asude, Tektemur Ahmet, Melek Elif, Kayfeci Mustafa, Uslu Muhammed F, Cosar Ugurcan, Onalan Ebru
Department of Medical Oncology, Medical Faculty, Firat University, Elazig, Turkey.
Department of Medical Biology and Genetics, Medical Faculty, Firat University, Elazig, Turkey.
Contemp Oncol (Pozn). 2020;24(4):241-246. doi: 10.5114/wo.2020.102826. Epub 2021 Jan 4.
The impaired balance between cell proliferation and cell death, followed the inability to receive the death signals, cells push towards the neoplasia pathway. Fibulin 1 (FBLN1) plays a role as a co-factor in the mechanism of action of a protease such as a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS-1), which has important roles in angiogenesis, can also act as both tumor suppressor gene (TSG) and an oncogene in the main constituent of the extra-cellular matrix. This preliminary study has investigated the effects of silencing FBLN1 with siRNA on autophagy, proliferation, apoptosis pathways in the MSM cell line.
It was transfected siRNA specific to FBLN1 incubated MSM SPC212 cells, and compared with negative control siRNAs by a real-time polymerase chain reaction. It was determined apoptosis, proliferation, autophagy-related genes in mRNA levels.
It was observed that increased anti-apoptosis genes, such as , and , anti-apoptotic gene, reduced . Proliferation induced through while increased genes. Autophagy increased via increasing genes while decreased via suppressed , and genes by silencing FBLN1 with siRNAs ( < 0.05).
Proliferation can be induction with silencing of FBLN1 with siRNA in processing mechanism MSM. It was concluded that FBLN1 could be act as pleiotropic on autophagy, and apoptosis pathways in proliferation processing for MSM. Therefore we think that FBLN1 acts like a TSG. FBLN1 can be considered as a targeted treatment option in advanced stage MSM.
细胞增殖与细胞死亡之间的平衡受损,继之无法接收死亡信号,细胞便会朝着肿瘤形成途径发展。纤连蛋白1(FBLN1)在诸如含血小板反应蛋白基序的解聚素和金属蛋白酶(ADAMTS-1)等蛋白酶的作用机制中作为辅助因子发挥作用,ADAMTS-1在血管生成中具有重要作用,在细胞外基质的主要成分中也可同时作为肿瘤抑制基因(TSG)和癌基因。本初步研究调查了用小干扰RNA(siRNA)沉默FBLN1对MSM细胞系自噬、增殖、凋亡途径的影响。
用针对FBLN1的siRNA转染培养的MSM SPC212细胞,并通过实时聚合酶链反应与阴性对照siRNA进行比较。测定mRNA水平上凋亡、增殖、自噬相关基因。
观察到抗凋亡基因如 、 和 增加,抗凋亡基因 减少。 诱导增殖,同时 基因增加。自噬通过增加 基因而增加,而通过沉默FBLN1的siRNA抑制 、 和 基因导致自噬减少( < 0.05)。
在MSM的作用机制中,用siRNA沉默FBLN1可诱导增殖。得出结论,FBLN1在MSM增殖过程中的自噬和凋亡途径中可能具有多效性。因此我们认为FBLN1起着肿瘤抑制基因的作用。FBLN1可被视为晚期MSM的靶向治疗选择。