摘要
小核核糖核蛋白(small nuclear ribonucleoprotein polypeptide A,SNRPA1)参与mRNA加工剪接体(splicesome)的组装,与多种肿瘤的发生有关,但在肝癌发生发展过程中的分子机制尚不明确。该研究利用基因芯片技术探究SNRPA1敲减后肝癌细胞信号通路关键基因的表达动态,及其在裸鼠肿瘤发生发展中的分子机制。研究结果显示,与对照组相比,SNRPA1基因敲减后的低表达组裸鼠的荷瘤细胞的生长受到显著抑制;基因芯片分析表明,SNRPA1的敲低导致462个基因的表达下调,262个基因的表达上调。qRT-PCR分析表明,FSTL1、FGF2、JAK2、WNT5A和PPM1A基因表达均有所降低,而Western blot分析进一步证实FSTL1、JAK2、WNT5A蛋白质表达的下调。以上结果可知,SNPRA1作为促癌基因,可能通过调控多种基因的表达及信号通路对肝细胞肝癌的发生和发展进行调控。
SNRPA1 (small nuclear ribonucleoprotein A) is involved in assembly of mRNA-processed splicesome and associated with tumorigenesis of many tumors.However,it’s function in the molecular mechanism for tumorigenicity of HCC (hepatocellular carcinoma) remains unclear.In this study,gene chip technology was used to explore the expression dynamics of key genes in HCC cell signaling pathway after SNRPA1 knockdown,and its molecular mechanism for regulating the development of HCC in nude mice.The results of optical in vivo imaging showed that the growth of SNRPA1 deleted HCC in nude mice was significantly inhibited compared with the control group.Gene chip analysis showed that knockdown of SNRPA1 led to 462 genes down-regulation and 262 genes up-regulation.qRT-PCR analysis showed that the expression of FSTL1,FGF2,JAK2,WNT5A and PPM1A were all decreased,while Western blot analysis further confirmed that the expression of FSTL1,JAK2,WNT5A were down-regulated.The above results show that SNPRA1,as a pro-oncogene,may be involved in the tumorigenicity and development of hepatocellular carcinoma through regulating multiple genes and signal pathways.
作者
冯璟
王俊平
柴宝峰
FENG Jing;WANG Junping;CHAI Baofeng(Institute of Loess Plateau,Shanxi University,Taiyuan 030006,China;Department of Gastroenterology,Affiliated People's Hospital of Shanxi Medical University,Shanxi Institute of Gastroenterology,Taiyuan 030012,China)
出处
《中国细胞生物学学报》
CAS
CSCD
2020年第5期839-848,共10页
Chinese Journal of Cell Biology
基金
国家自然科学基金(批准号:31772450)资助的课题。
