The aberrant expression of human sirtuin 2 (SIRT2) has been detected in various types of cancer; however, the biological roles, underlying mechanisms and clinical significance of SIRT2 dysregulation in human colorectal cancer (CRC) remain unclear. The results of this study demonstrate that compared with paired normal tissues, SIRT2 expression is significantly decreased in CRC tissues. SIRT2 loss has been correlated with clinicopathological characteristics, including distant metastasis, lymph node metastasis and American Joint Committee on Cancer (AJCC) stage; this loss serves as an independent factor that indicates a poor prognosis for patients with CRC. Further gain‐ and loss‐of‐function analyses have demonstrated that SIRT2 suppresses CRC cell proliferation and metastasis both in vivo and in vitro. Mechanistically, miR‐212‐5p was identified to directly target the SIRT2 3′‐untranslated region (3′‐UTR), leading to SIRT2 down‐regulation. The ectopic expression of SIRT2 reverses the effect of miR‐212‐5p overexpression on CRC cell colony formation, invasion, migration and proliferation. Clinically, an inverse correlation was found between miR‐212‐5p and SIRT2 expression. High miR‐212‐5p expression has been found to result in a poor prognosis and aggressive clinicopathological characteristics in patients with CRC. Taken together, these results suggest that SIRT2, targeted by miR‐212‐5p, acts as a tumour suppressor in CRC and that the miR‐212‐5p/SIRT2 axis is a promising prognostic factor and potential therapeutic target in CRC.

中文翻译：

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SIRT2是miR-212-5p的直接靶标，可抑制结直肠癌细胞的增殖和转移。

已经在各种类型的癌症中检测到人类sirtuin 2（SIRT2）的异常表达。然而，SIRT2失调在人类大肠癌（CRC）中的生物学作用，潜在机制和临床意义仍不清楚。这项研究的结果表明，与成对的正常组织相比，SIRT2在CRC组织中的表达明显降低。SIRT2丢失与临床病理特征有关，包括远处转移，淋巴结转移和美国癌症联合委员会（AJCC）分期；这种丢失是表明CRC患者预后不良的独立因素。进一步的功能获得和丧失功能分析表明，SIRT2在体内和体外均能抑制CRC细胞的增殖和转移。机械上，miR-212-5p被确定为直接靶向SIRT2 3'-非翻译区（3'-UTR），从而导致SIRT2下调。SIRT2的异位表达逆转了miR-212-5p过表达对CRC细胞集落形成，侵袭，迁移和增殖的影响。临床上，发现miR-212-5p与SIRT2表达呈反相关。已发现高表达miR‐212‐5p会导致CRC患者预后不良和侵袭性的临床病理特征。综上所述，这些结果表明，以miR-212-5p为靶标的SIRT2在CRC中起着肿瘤抑制作用，而miR-212-5p / SIRT2轴在CRC中是有希望的预后因素和潜在的治疗靶标。SIRT2的异位表达逆转了miR-212-5p过表达对CRC细胞集落形成，侵袭，迁移和增殖的影响。临床上，发现miR-212-5p与SIRT2表达呈反相关。已发现高表达miR‐212‐5p会导致CRC患者预后不良和侵袭性的临床病理特征。综上所述，这些结果表明，以miR-212-5p为靶标的SIRT2在CRC中起着肿瘤抑制作用，而miR-212-5p / SIRT2轴在CRC中是有希望的预后因素和潜在的治疗靶标。SIRT2的异位表达逆转了miR-212-5p过表达对CRC细胞集落形成，侵袭，迁移和增殖的影响。临床上，发现miR-212-5p与SIRT2表达呈反相关。已发现高表达miR‐212‐5p会导致CRC患者预后不良和侵袭性的临床病理特征。综上所述，这些结果表明，以miR-212-5p为靶标的SIRT2在CRC中起着肿瘤抑制作用，而miR-212-5p / SIRT2轴在CRC中是有希望的预后因素和潜在的治疗靶标。已发现高表达miR‐212‐5p会导致CRC患者预后不良和侵袭性的临床病理特征。综上所述，这些结果表明，以miR-212-5p为靶标的SIRT2在CRC中起着肿瘤抑制作用，而miR-212-5p / SIRT2轴在CRC中是有希望的预后因素和潜在的治疗靶标。已发现高表达miR‐212‐5p会导致CRC患者预后不良和侵袭性的临床病理特征。综上所述，这些结果表明，以miR-212-5p为靶标的SIRT2在CRC中起着肿瘤抑制作用，而miR-212-5p / SIRT2轴在CRC中是有希望的预后因素和潜在的治疗靶标。