To understand how upregulated isoglutaminyl cyclase (isoQC) is involved in the initiation of diseases such as cancer, we developed a human KYSE30 carcinoma cell model in which isoQC was stably overexpressed. GO and KEGG analysis of the DEGs (228) and DEPs (254) respectively implicated isoQC on the proliferation invasion and metastasis of cells and suggested that isoQC might participate in the regulation of MAPK, RAS, circadian rhythm, and related pathways. At the functional level, isoQC-overexpressing KYSE30 cells showed enhanced proliferation, migration, and invasion capacity. Next, we decided to study the precise effect of isoQC overexpression on JNK, p-JNK, AKT, p-AKT, ERK, p-ERK, and PER2, as RNA levels of these proteins are significantly correlated with signal levels indicated in RNA-Seq analysis, and these candidates are the top correlated DEPs enriched in RT-qPCR analysis. We saw that only p-ERK expression was inhibited, while PER2 was increased. These phenotypes were inhibited upon exposure to PER2 inhibitor KL044, which allowed for the restoration of p-ERK levels. These data support upregulated isoQC being able to promote cancer cell proliferation and migration in vitro, likely by helping to regulate the MAPK and RAS signaling pathways, and the circadian protein PER2 might be a potential mediator.

中文翻译：

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异谷氨酰胺环化酶过表达通过 MAPK 信号通路增强 KYSE30 癌细胞增殖和迁移

为了了解上调的异谷氨酰胺环化酶 (isoQC) 如何参与癌症等疾病的发生，我们开发了一种人类 KYSE30 癌细胞模型，其中 isoQC 稳定过表达。对DEGs（228）和DEPs（254）的GO和KEGG分析分别表明isoQC与细胞的增殖、侵袭和转移有关，提示isoQC可能参与MAPK、RAS、昼夜节律和相关通路的调节。在功能水平上，isoQC过表达的KYSE30细胞显示出增强的增殖、迁移和侵袭能力。接下来，我们决定研究 isoQC 过表达对 JNK、p-JNK、AKT、p-AKT、ERK、p-ERK 和 PER2 的精确影响，因为这些蛋白质的 RNA 水平与 RNA-中所示的信号水平显着相关。 Seq 分析，这些候选者是 RT-qPCR 分析中富集的最相关的 DEP。我们看到只有 p-ERK 表达受到抑制，而 PER2 表达增加。这些表型在暴露于 PER2 抑制剂 KL044 后受到抑制，从而恢复 p-ERK 水平。这些数据支持上调的 isoQC 能够在体外促进癌细胞增殖和迁移，可能是通过帮助调节 MAPK 和 RAS 信号通路，而昼夜节律蛋白 PER2 可能是一种潜在的介质。