SMARCA

SMARCA
  • 文章类型: Journal Article
    SMARCAs,属于SWI/SNF2亚家族,由于它们对染色质重塑过程的调节,对细胞过程至关重要。尽管SMARCAs与各种癌症类型的肿瘤进展有关,我们对这些成员如何影响胰腺癌发生的理解非常有限,提高这一点需要生物信息学分析和生物学方法。
    为了解决这个问题,我们使用ONCOMINE研究了胰腺癌患者SMARCAs的转录和生存数据,GEPIA,人类蛋白质图谱,和Kaplan-Meier绘图仪.我们通过功能实验进一步验证了生物标志物在体外对胰腺癌的作用。
    Kaplan-Meier曲线和对数秩检验分析显示SMARCA1/2/3/SMARCAD1与患者总生存期(OS)呈正相关。另一方面,SMARCA6(又称HELLS)mRNA表达与OS呈负相关。同时,SMARCA4/5/SMARCAL1与肿瘤分期和OS无显著相关性。HELLS的击倒损害了集落形成能力,并通过将细胞阻滞在S期来抑制胰腺癌细胞的增殖。
    数据挖掘分析和细胞功能研究表明,HELLS在胰腺癌的发生发展中起着致癌作用。并作为胰腺癌预后不良的生物标志物。我们的工作为HELLS在胰腺癌中的进一步临床应用奠定了基础。
    SMARCAs, belonged to SWI/SNF2 subfamilies, are critical to cellular processes due to their modulation of chromatin remodeling processes. Although SMARCAs are implicated in the tumor progression of various cancer types, our understanding of how those members affect pancreatic carcinogenesis is quite limited and improving this requires bioinformatics analysis and biology approaches.
    To address this issue, we investigated the transcriptional and survival data of SMARCAs in patients with pancreatic cancer using ONCOMINE, GEPIA, Human Protein Atlas, and Kaplan-Meier plotter. We further verified the effect of significant biomarker on pancreatic cancer in vitro through functional experiment.
    The Kaplan-Meier curve and log-rank test analyses showed a positive correlation between SMARCA1/2/3/SMARCAD1 and patients\' overall survival (OS). On the other hand, mRNA expression of SMARCA6 (also known as HELLS) showed a negative correlation with OS. Meanwhile, no significant correlation was found between SMARCA4/5/SMARCAL1 and tumor stages and OS. The knockdown of HELLS impaired the colony formation ability, and inhibited pancreatic cancer cell proliferation by arresting cells at S phase.
    Data mining analysis and cell function research demonstrated that HELLS played oncogenic roles in the development and progression of pancreatic cancer, and serve as a poor prognostic biomarker for pancreatic cancer. Our work laid a foundation for further clinical applications of HELLS in pancreatic cancer.
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