Department of Colorectal Surgery, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China.
Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, 310000, China.
Surg Oncol. 2019 Dec;31:67-74. doi: 10.1016/j.suronc.2019.09.009. Epub 2019 Sep 13.
The molecular mechanisms governing the metastasis of colorectal cancer (CRC) are incompletely understood. In the present study, we found NOVA1 to be expressed at higher levels in CRC cell lines and tissue samples, and this upregulation was positively correlated with TNM stage (p = 0.034), poor differentiation (p = 0.001), and lymph node metastasis (p = 0.008). Both overall survival (OS) and relapse-free survival (RFS) were both significantly decreased in patients with high NOVA1 expression relative to those with low expression. Through a multivariate analysis, we determined that NOVA1 independently predicted poor outcomes in those with CRC. In further functional studies, we found that NOVA1 expression controlled the proliferation and invasive characteristics of CRC cells via a mechanism wherein NOVA1 bound and stabilized the IL6 mRNA, enhancing IL-6/JAK2/STAT3 signaling to in turn upregulate matrix metalloproteinases (MMPs) 2, 7, and 9. NOVA1 therefore plays key functional roles in regulating CRC progression, and our results further indicate that it serve as a valuable prognostic biomarker and potentially a target for therapeutic treatment in individuals with CRC.
结直肠癌（CRC）转移的分子机制尚不完全清楚。在本研究中，我们发现 NOVA1 在 CRC 细胞系和组织样本中的表达水平更高，这种上调与 TNM 分期（p=0.034）、分化不良（p=0.001）和淋巴结转移（p=0.008）呈正相关。NOVA1 高表达的患者的总生存（OS）和无复发生存（RFS）均明显低于低表达的患者。通过多变量分析，我们确定 NOVA1 独立预测 CRC 患者预后不良。在进一步的功能研究中，我们发现 NOVA1 通过一种机制控制 CRC 细胞的增殖和侵袭特征，其中 NOVA1 结合并稳定 IL6 mRNA，增强 IL-6/JAK2/STAT3 信号通路，从而上调基质金属蛋白酶（MMPs）2、7 和 9。NOVA1 因此在调节 CRC 进展中发挥关键功能作用，我们的结果进一步表明，它可作为 CRC 患者有价值的预后生物标志物和潜在的治疗靶点。
