Aim. The aim of this study was to investigate the effect and underlying pathway of pyrroline-5-carboxylate reductase-2 (PYCR2) on colorectal cancer (CRC). Methods. The Cancer Genome Atlas (TCGA) database was used to analyze PYCR2 expression levels and clinical information. Cell proliferation was evaluated using colony forming and EdU assay. Cell apoptosis rate was determined using flow cytometry. Cell migration and invasion were measured by performing a Transwell assay, and PYCR2, MMP-2, MMP-9, Bax, cleaved caspase-3, Bcl-2, cleaved PARP, p-PI3K, PI3K, p-AKT, AKT, p-mTOR, and mTOR protein levels were detected by Western blot. Results. A review of the TCGA database revealed that PYCR2 was highly expressed in CRC patients and that high PYCR2 expression was associated with advanced stage, adenocarcinoma, nodal metastasis, and poor survival rate. Moreover, PYCR2 knockdown reduced cell viability, proliferation, migration, and invasion and increased apoptosis. Additionally, PYCR2 knockdown increased Bax, cleaved caspase-3, and cleaved PARP levels and decreased Bcl-2, MMP-2, MMP-9, p-PI3K, p-AKT, and p-mTOR levels in CRC cells. Effects of silencing PYCR2 on proliferation, migration, invasion, apoptosis, and the PI3K/AKT/mTOR pathway in CRC cells were all reversed using a PI3K activator (740Y-P). Conclusion. PYCR2 was highly expressed in CRC, and its knockdown suppressed CRC tumorigenesis via inhibiting the activation of PI3K/AKT/mTOR pathway. This finding provides a new theoretical foundation for the treatment of CRC.

中文翻译：

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Pyrroline-5-Carboxylate Reductase-2 通过激活 PI3K/AKT/mTOR 通路促进结直肠癌进展

瞄准。本研究的目的是研究 pyrroline-5-carboxylate reductase-2 (PYCR2) 对结直肠癌 (CRC) 的影响和潜在途径。方法。癌症基因组图谱（TCGA）数据库用于分析 PYCR2 表达水平和临床信息。使用集落形成和EdU测定评估细胞增殖。使用流式细胞术测定细胞凋亡率。通过进行 Transwell 测定和 PYCR2、MMP-2、MMP-9、Bax、cleaved caspase-3、Bcl-2、cleaved PARP、p-PI3K、PI3K、p-AKT、AKT、p 来测量细胞迁移和侵袭Western blot检测-mTOR和mTOR蛋白水平。结果. 对 TCGA 数据库的回顾显示，PYCR2 在 CRC 患者中高表达，并且 PYCR2 高表达与晚期、腺癌、淋巴结转移和低生存率相关。此外，PYCR2 敲低降低了细胞活力、增殖、迁移和侵袭，并增加了细胞凋亡。此外，PYCR2 敲低增加了 CRC 细胞中的 Bax、cleaved caspase-3 和 cleaved PARP 水平，并降低了 Bcl-2、MMP-2、MMP-9、p-PI3K、p-AKT 和 p-mTOR 水平。使用 PI3K 激活剂 (740Y-P) 可逆转沉默 PYCR2 对 CRC 细胞增殖、迁移、侵袭、凋亡和 PI3K/AKT/mTOR 通路的影响。结论. PYCR2 在 CRC 中高表达，其敲低通过抑制 PI3K/AKT/mTOR 通路的激活来抑制 CRC 肿瘤发生。这一发现为CRC的治疗提供了新的理论基础。