Shang Bin, Lu Fengjuan, Jiang Shujuan, Xing Mengmeng, Mao Xinyu, Yang Guanghai, Zhang Hao
Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong Province, China.
Department of Respiratory and Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong Province, China.
Aging (Albany NY). 2023 Sep 18;15(18):9614-9632. doi: 10.18632/aging.205038.
Despite advancements in therapeutic options, the overall prognosis for non-small cell lung cancer (NSCLC) remains poor. Therefore, it is crucial to further explore the etiology and targets for novel treatments to effectively manage NSCLC. In this study, immunohistochemistry was used to analyze the expression of aldolase, fructose-bisphosphate C (ALDOC) protein in tumor tissues and adjacent non-malignant tissues from 79 NSCLC patients. Our findings revealed that ALDOC was overexpressed in NSCLC tissues. ALDOC expression was associated with lymph node metastasis, lymphatic metastasis and pathological stage. In addition, Kaplan-Meier analysis showed that higher ALDOC levels were indicative of a poorer prognosis. Additionally, we observed elevated ALDOC mRNA levels in NSCLC cell lines relative to normal cells. To investigate the functional roles of ALDOC, we infected cells with small interfering RNA against ALDOC, which led to attenuated proliferation and migration, as well as ameliorated apoptosis. Furthermore, through our investigations, we discovered that ubiquitin-conjugating enzyme E2N (UBE2N) acts as a downstream factor of ALDOC. ALDOC promoted NSCLC through affecting MYC-mediated UBE2N transcription and regulating the Wnt pathway. More importantly, we found that downregulation of UBE2N or the use of Wnt pathway inhibitor could reverse the promoting effects of ALDOC elevation on NSCLC development and . Based on these findings, our study highlights the potential of ALDOC as a future therapeutic target for NSCLC.
尽管治疗方案有所进步，但非小细胞肺癌（NSCLC）的总体预后仍然很差。因此，进一步探索其病因和新治疗靶点对于有效治疗NSCLC至关重要。在本研究中，采用免疫组织化学法分析了79例NSCLC患者肿瘤组织及癌旁非恶性组织中醛缩酶、果糖-1,6-二磷酸C（ALDOC）蛋白的表达。我们的研究结果显示，NSCLC组织中ALDOC过表达。ALDOC表达与淋巴结转移、淋巴转移及病理分期相关。此外，Kaplan-Meier分析表明，较高的ALDOC水平预示着较差的预后。另外，我们观察到NSCLC细胞系中ALDOC mRNA水平相对于正常细胞有所升高。为了研究ALDOC的功能作用，我们用针对ALDOC的小干扰RNA感染细胞，这导致细胞增殖和迁移减弱，以及细胞凋亡改善。此外，通过我们的研究，我们发现泛素结合酶E2N（UBE2N）是ALDOC的下游因子。ALDOC通过影响MYC介导的UBE2N转录和调节Wnt通路来促进NSCLC。更重要的是，我们发现下调UBE2N或使用Wnt通路抑制剂可以逆转ALDOC升高对NSCLC发展的促进作用。基于这些发现，我们的研究突出了ALDOC作为NSCLC未来治疗靶点的潜力。
