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PYCR1 knockdown inhibits the proliferation, migration, and invasion by affecting JAK/STAT signaling pathway in lung adenocarcinoma.
Molecular Carcinogenesis ( IF 4.6 ) Pub Date : 2020-03-04 , DOI: 10.1002/mc.23174
Yawen Gao 1 , Lihua Luo 2 , Yangchun Xie 1 , Yu Zhao 3 , Jie Yao 4 , Xianling Liu 1
Affiliation  

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:

PYCR1敲低通过影响肺腺癌中的JAK / STAT信号通路来抑制增殖,迁移和侵袭。

肺腺癌(LUAD)作为非小细胞肺癌(NSCLC)的一种形式,是全世界诊断最频繁的肺癌。迄今为止,已经报道了一些生物标志物,可为指导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。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LUAD细胞系和患者组织中PYCR1表达的异常增加。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,LUAD患者中PYCR1过表达与预后不良有关。为了进一步研究PYCR1在LUAD中的功能,细胞计数试剂盒8,集落形成,刮擦伤口愈合,并进行Transwell测定。结果表明,敲除PYCR1可以抑制LUAD细胞系中的细胞增殖,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途径富集分析。在这些丰富的途径中,我们选择了JAK / STAT信号传导途径进行进一步分析。Western印迹分析的结果表明,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,该研究发掘了PYCR1基因敲低可以抑制肿瘤的生长并影响LUAD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。
更新日期:2020-04-13
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