Background

Pyrroline-5-carboxylate reductase 2 (PYCR2) expression is aberrantly upregulated in colon cancer. However, the functions and underlying mechanisms of PYCR2 in breast cancer remain elusive. The primary objective of the present study was to elucidate the function of PYCR2 in breast cancer and investigate whether PYCR2 may be transcriptionally regulated by c-Myc to activate the AKT signaling pathway.

Methods

Immunohistochemical analysis was performed to examine the expression of PYCR2 in breast cancer and adjacent non-cancerous tissues. Western blot and RT-qPCR were utilized to detect PYCR2 expression in breast cancer cells. Cellular functionalities were evaluated through Transwell assays in vitro and lung metastasis formation assays in vivo. Moreover, the impact of PYCR2 on the activation of AKT signaling was determined through western blot and immunohistochemistry analysis. The transcriptional regulation of PYCR2 expression by c-Myc was evaluated via both western blot analysis and luciferase gene reporter assay.

Results

PYCR2 overexpression was noted in breast cancer. Silencing PYCR2 expression attenuated the invasive and metastatic abilities of breast cancer cells. Furthermore, the activation of the AKT signaling pathway is indispensable for the promotion of invasion and metastasis mediated by PYCR2. Lastly, the binding of c-Myc to the promoter sequence of PYCR2 resulted in the upregulation of PYCR2 transcription.

Conclusion

Taken together, these results indicate that PYCR2 is transcriptionally regulated by c-Myc and promotes invasion and metastasis in breast cancer through the activation of the AKT pathway.

中文翻译：

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c-Myc诱导的PYCR2通过激活AKT信号通路促进乳腺癌的侵袭和转移

背景

吡咯啉-5-羧酸还原酶 2 (PYCR2) 表达在结肠癌中异常上调。然而，PYCR2 在乳腺癌中的功能和潜在机制仍不清楚。本研究的主要目的是阐明 PYCR2 在乳腺癌中的功能，并研究 PYCR2 是否可能受 c-Myc 转录调控以激活 AKT 信号通路。

方法

进行免疫组织化学分析以检查 PYCR2 在乳腺癌和邻近非癌组织中的表达。采用Western blot和RT-qPCR检测乳腺癌细胞中PYCR2的表达。通过体外Transwell实验和体内肺转移形成实验评估细胞功能。此外，通过蛋白质印迹和免疫组织化学分析确定了 PYCR2 对 AKT 信号传导激活的影响。通过蛋白质印迹分析和荧光素酶基因报告测定评估 c-Myc 对 PYCR2 表达的转录调节。

结果

PYCR2 在乳腺癌中过度表达。沉默 PYCR2 表达会减弱乳腺癌细胞的侵袭和转移能力。此外，AKT信号通路的激活对于促进PYCR2介导的侵袭和转移是必不可少的。最后，c-Myc 与 PYCR2 启动子序列的结合导致 PYCR2 转录上调。

结论

综上所述，这些结果表明 PYCR2 受 c-Myc 转录调控，并通过 AKT 通路的激活促进乳腺癌的侵袭和转移。