Colorectal cancer (CRC) is a common malignancy. Many reports have implicated aberrant mitochondrial activity in the progression of CRC, with particular emphasis on the dysregulation of redox signaling and oxidative stress. In this study, we focused on manganese superoxide dismutase (MnSOD/SOD2), a key antioxidant enzyme, which maintains intracellular redox homeostasis. Current literature presents conflicting mechanisms for how SOD2 influences tumorigenesis and tumor progression. Here, we explored the role of SOD2 in CRC specifically. We found high levels of SOD2 expression in CRC tissues. We carried out a series of experiments to determine whether knockdown of SOD2 expression in CRC cell lines would reverse features of tumorigenesis. We found that reduced SOD2 expression decreased cell proliferation, migration, and invasion activity in CRC cells. Results from an additional series of experiments on mitochondrial function implicated a dual role for SOD2 in promoting CRC progression. First, proper level of SOD2 helped CRC cells maintain mitochondrial function by disposal of superoxide (O₂^.−). Second, over‐expression of SOD2 induced H₂O₂‐mediated tumorigenesis by upregulating AMPK and glycolysis. Our results indicate that SOD2 may promote the occurrence and development of CRC by regulating the energy metabolism mediated by AMPK signaling pathways.

中文翻译：

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SOD2 的氧化还原调节通过 AMPK 介导的能量代谢调节结直肠癌肿瘤发生。

结直肠癌（CRC）是一种常见的恶性肿瘤。许多报告表明线粒体活性异常与结直肠癌的进展有关，特别强调氧化还原信号传导和氧化应激的失调。在这项研究中，我们重点关注锰超氧化物歧化酶（MnSOD/SOD2），这是一种关键的抗氧化酶，可维持细胞内氧化还原稳态。目前的文献对于 SOD2 如何影响肿瘤发生和肿瘤进展提出了相互矛盾的机制。在这里，我们具体探讨了 SOD2 在 CRC 中的作用。我们发现 CRC 组织中 SOD2 表达水平较高。我们进行了一系列实验，以确定 CRC 细胞系中 SOD2 表达的敲低是否会逆转肿瘤发生的特征。我们发现 SOD2 表达减少会降低 CRC 细胞的增殖、迁移和侵袭活性。其他一系列关于线粒体功能的实验结果表明 SOD2 在促进 CRC 进展中具有双重作用。首先，适当水平的 SOD2 有助于 CRC 细胞通过处理超氧化物（O₂ ^.− )。其次，SOD2 的过度表达通过上调 AMPK 和糖酵解诱导 H ₂ O _{2介导的肿瘤发生。}我们的研究结果表明SOD2可能通过调节AMPK信号通路介导的能量代谢促进CRC的发生和发展。