Lung adenocarcinoma (LUAD), as a form of non‐small cell lung cancer (NSCLC), is the most frequently diagnosed lung cancer worldwide. To date, a few biomarkers have been reported to provide valuable information in guiding LUAD treatment. The aim of our study was to explore the functional role of pyrroline‐5‐carboxylate reductase 1 (PYCR1) in LUAD. Based on Oncomine database, we found that PYCR1 was highly expressed in LUAD tissues. We also confirmed an abnormal increase of PYCR1 expression in LUAD cell lines and patients' tissues. Through Kaplan‐Meier plotter database, we further studied the prognostic values of PYCR1. The outcomes indicated that overexpressed PYCR1 associated with poor prognosis among LUAD patients. To further study the function of PYCR1 in LUAD, cell counting kit‐8, colony‐forming, scratch wound healing, and Transwell assays were conducted. The results suggested that knockdown of PYCR1 curbed cell proliferation, migration, and invasion in LUAD cell lines. Subsequently, we identified 50 top genes positively and negatively correlated with PYCR1 in LUAD, and conducted biological pathway enrichment analysis of these genes. Among those enriched pathways, we selected JAK/STAT signaling pathway for further analysis. The results of Western blot assays revealed that PYCR1 knockdown significantly increased the expression of Bcl‐2 and c‐Myc, and the phosphorylation level of JAK2 and STAT3. Taken together, this study unearthed that PYCR1 knockdown could inhibit tumor growth and affect the JAK/STAT signaling pathway in LUAD. This study may contribute to a better understanding of PYCR1 in LUAD and provide a potential biomarker for cancer prognosis.

中文翻译：

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PYCR1敲低通过影响JAK/STAT信号通路抑制肺腺癌的增殖、迁移和侵袭。


肺腺癌（LUAD）是非小细胞肺癌（NSCLC）的一种形式，是全世界最常诊断的肺癌。迄今为止，据报道一些生物标志物可以为指导 LUAD 治疗提供有价值的信息。我们研究的目的是探讨吡咯啉-5-羧酸还原酶 1 (PYCR1) 在 LUAD 中的功能作用。基于Oncomine数据库，我们发现PYCR1在LUAD组织中高表达。我们还证实 LUAD 细胞系和患者组织中 PYCR1 表达异常增加。通过Kaplan-Meier绘图仪数据库，我们进一步研究了PYCR1的预后价值。结果表明，PYCR1 过度表达与 LUAD 患者预后不良相关。为了进一步研究 PYCR1 在 LUAD 中的功能，进行了细胞计数试剂盒 8、集落形成、划痕愈合和 Transwell 测定。结果表明，PYCR1 的敲除抑制了 LUAD 细胞系的细胞增殖、迁移和侵袭。随后，我们在LUAD中鉴定了50个与PYCR1正相关和负相关的顶级基因，并对这些基因进行了生物通路富集分析。在这些富集的通路中，我们选择JAK/STAT信号通路进行进一步分析。 Western blot检测结果显示，PYCR1敲低显着增加了Bcl-2和c-Myc的表达，以及JAK2和STAT3的磷酸化水平。综上所述，本研究发现 PYCR1 敲低可以抑制肿瘤生长并影响 LUAD 中的 JAK/STAT 信号通路。这项研究可能有助于更好地了解 LUAD 中的 PYCR1，并为癌症预后提供潜在的生物标志物。