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.

中文翻译：

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HELLS 作为预后不良的生物标志物，其下调保留了胰腺癌的恶性表型

SMARCAs 属于 SWI/SNF2 亚家族，由于其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，但我们对这些成员如何影响胰腺癌发生的理解非常有限，改进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、GEPIA、人类蛋白质图谱和 Kaplan-Meier 绘图仪研究了胰腺癌患者中 SMARCA 的转录和生存数据。我们通过功能实验进一步验证了显着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/SMARCA1 与患者的总生存期 (OS) 呈正相关。另一方面，SMARCA6（也称为HELLS）的mRNA表达与OS呈负相关。同时，SMARCA4/5/SMARCAL1与肿瘤分期和OS之间无显着相关性。HELLS的敲低损害了集落形成能力，并通过将细胞停滞在S期来抑制胰腺癌细胞增殖。数据挖掘分析和细胞功能研究表明，HELLS 在胰腺癌的发展和进展中发挥致癌作用，是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。HELLS的敲低损害了集落形成能力，并通过将细胞停滞在S期来抑制胰腺癌细胞增殖。数据挖掘分析和细胞功能研究表明，HELLS 在胰腺癌的发展和进展中发挥致癌作用，是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。HELLS的敲低损害了集落形成能力，并通过将细胞停滞在S期来抑制胰腺癌细胞增殖。数据挖掘分析和细胞功能研究表明，HELLS 在胰腺癌的发展和进展中发挥致癌作用，是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。