Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, NO. 188, Shizi Street, Suzhou, 215006, People's Republic of China.
Department of Thoracic Surgery, Shanghai Pudong New Area People's Hospital, Shanghai University of Medicine and Health Sciences, Shanghai, 201318, People's Republic of China.
World J Surg Oncol. 2022 May 21;20(1):162. doi: 10.1186/s12957-022-02599-x.
Non-small cell lung cancer (NSCLC) causes numerous deaths worldwide. however, biomarkers for NSCLC prognosis are scarce for its heterogeneity. Proteins containing the RING finger domain RING finger protein 180 (RNF180) is a key mediator for ubiquitination, which controls cell cycle and regulates progression in certain human tumors. However, the detailed function of RNF180 in NSCLC remains unclear. In the present study, we aimed to investigate the role of RNF180 and its molecule network in NSCLC.
Quantitative real-time polymerase chain reaction and immunohistochemical staining were used to analyze RNF180 levels. RNA interference and lentiviral-mediated vector transfections were performed to silence and overexpress RNF180 in NSCLC cells. Furthermore, Cell Counting Kit-8 was used for assessing biological function of RNF180 in cell proliferation and a xenograft model for examining its function in vivo. The activity of glycolysis was determined by examining the level of the extracellular acidification rate (ECAR).
RNF180 expression decreased in NSCLC tissues, and its expression was positively correlated with the survival rate of patients with NSCLC. Moreover, RNF180 overexpression suppressed the proliferation and glycolytic activities in NSCLC cells and restricted its tumorigenicity in vivo. Furthermore, RNF180 silencing promoted the proliferation and glycolysis metabolism of NSCLC cells, whereas C-myc inhibitor disrupted these effects. The underlying anti-oncogene of RNF180 involved in C-myc downregulation via ubiquitin-dependent degradation.
Together, these results firstly indicated the anti-tumor properties of RNF180 and its correlation with NSCLC progression, thereby endorsing the potential role of RNF180 as an efficient prognostic biomarker for tumor recurrence.
非小细胞肺癌（NSCLC）在全球范围内导致了大量死亡。然而，由于其异质性，NSCLC 的预后生物标志物仍然匮乏。含环指结构域的 RING finger 蛋白 180（RNF180）是泛素化的关键介质，可控制细胞周期并调节某些人类肿瘤的进展。然而，RNF180 在 NSCLC 中的详细功能仍不清楚。在本研究中，我们旨在研究 RNF180 及其分子网络在 NSCLC 中的作用。
使用定量实时聚合酶链反应和免疫组织化学染色来分析 RNF180 水平。通过 RNA 干扰和慢病毒介导的载体转染在 NSCLC 细胞中沉默和过表达 RNF180。此外，使用细胞计数试剂盒-8 评估 RNF180 在细胞增殖中的生物学功能，并用异种移植模型检验其在体内的功能。通过检测细胞外酸化率（ECAR）来确定糖酵解的活性。
RNF180 在 NSCLC 组织中的表达降低，其表达与 NSCLC 患者的生存率呈正相关。此外，RNF180 过表达抑制了 NSCLC 细胞的增殖和糖酵解活性，并限制了其在体内的致瘤性。进一步的研究表明，沉默 RNF180 促进了 NSCLC 细胞的增殖和糖酵解代谢，而 C-myc 抑制剂则破坏了这些作用。RNF180 的抑癌作用涉及通过泛素依赖性降解下调 C-myc。
总之，这些结果首次表明了 RNF180 的抗肿瘤特性及其与 NSCLC 进展的相关性，从而支持 RNF180 作为肿瘤复发有效预后生物标志物的潜在作用。
