Department of Oncology, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China.
Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
Mol Carcinog. 2020 May;59(5):503-511. doi: 10.1002/mc.23174. Epub 2020 Mar 4.
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.
肺腺癌（LUAD）是一种非小细胞肺癌（NSCLC），是全球最常见的肺癌类型。迄今为止，已有一些生物标志物被报道可提供有价值的信息，以指导 LUAD 的治疗。本研究旨在探索吡咯啉-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。我们还证实了 PYCR1 在 LUAD 细胞系和患者组织中的异常表达增加。通过 Kaplan-Meier plotter 数据库，我们进一步研究了 PYCR1 的预后价值。结果表明，PYCR1 过表达与 LUAD 患者的不良预后相关。为了进一步研究 PYCR1 在 LUAD 中的功能，我们进行了细胞计数试剂盒-8（cell counting kit-8，CCK-8）、集落形成、划痕愈合和 Transwell 测定。结果表明，PYCR1 敲低可抑制 LUAD 细胞系的细胞增殖、迁移和侵袭。随后，我们鉴定了与 LUAD 中 PYCR1 呈正相关和负相关的 50 个 top 基因，并对这些基因进行了生物途径富集分析。在那些富集的途径中，我们选择 JAK/STAT 信号通路进行进一步分析。Western blot 分析结果表明，PYCR1 敲低显著增加了 Bcl-2 和 c-Myc 的表达，以及 JAK2 和 STAT3 的磷酸化水平。总之，本研究揭示了 PYCR1 敲低可抑制 LUAD 中的肿瘤生长并影响 JAK/STAT 信号通路。本研究可能有助于更好地理解 LUAD 中的 PYCR1，并为癌症预后提供潜在的生物标志物。
