ALDOC promotes non-small cell lung cancer through affecting MYC-mediated UBE2N transcription and regulating Wnt/β-catenin pathway.
ALDOC promotes non-small cell lung cancer through affecting MYC-mediated UBE2N transcription and regulating Wnt/β-catenin pathway.
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DOI：
10.18632/aging.205038
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发表时间：
2023-09-18
期刊：
影响因子：
5.2
通讯作者：
Zhang, Hao
中科院分区：
文献类型：
--
作者：
Shang, Bin;Lu, Fengjuan;Jiang, Shujuan;Xing, Mengmeng;Mao, Xinyu;Yang, Guanghai;Zhang, Hao
尽管治疗方案取得了进展，但非小细胞肺癌（NSCLC）的总体预后仍然很差。因此，进一步探索新的治疗方法的病因和靶点以有效管理NSCLC至关重要。本研究采用免疫组织化学方法检测79例NSCLC患者癌组织及癌旁组织中醛缩酶、二磷酸果糖C（ALDOC）蛋白的表达。我们的研究结果显示ALDOC在NSCLC组织中过表达。ALDOC的表达与淋巴结转移、淋巴结转移及病理分期有关。此外，Kaplan-Meier分析显示，ALDOC水平越高，预后越差。此外，我们观察到NSCLC细胞系中ALDOC mRNA水平相对于正常细胞升高。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，这导致增殖和迁移减弱，以及凋亡改善。此外，通过我们的研究，我们发现泛素结合酶E2 N（UBE 2N）作为ALDOC的下游因子。ALDOC通过影响MYC介导的UBE 2N转录和调节Wnt通路促进NSCLC的发生。更重要的是，我们发现下调UBE 2N或使用Wnt通路抑制剂可以逆转ALDOC升高对NSCLC体外和体内发展的促进作用。基于这些发现，我们的研究强调了ALDOC作为NSCLC未来治疗靶点的潜力。
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 in vitro and in vivo. Based on these findings, our study highlights the potential of ALDOC as a future therapeutic target for NSCLC.
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DOI：
10.15252/embj.201797311
发表时间：
2018-02-15
期刊：
The EMBO journal
影响因子：
--
作者：
Glaeser K;Urban M;Fenech E;Voloshanenko O;Kranz D;Lari F;Christianson JC;Boutros M
通讯作者：
Boutros M
影响因子：
11.8
作者：
Krishnamurthy N;Kurzrock R
通讯作者：
Kurzrock R
影响因子：
5.2
作者：
Chang, Yu-Chan;Tsai, Hsing-Fang;Tsai, Wen-Chivan
通讯作者：
Tsai, Wen-Chivan
UBE2N的小分子抑制剂通过激活p53和JNK途径诱导神经母细胞瘤死亡。
影响因子：
9
作者：
通讯作者：
--
影响因子：
120.7
作者：
Kris, Mark G.;Johnson, Bruce E.;Berry, Lynne D.;Kwiatkowski, David J.;Iafrate, A. John;Wistuba, Ignacio I.;Varella-Garcia, Marileila;Franklin, Wilbur A.;Aronson, Samuel L.;Su, Pei-Fang;Shyr, Yu;Camidge, D. Ross;Sequist, Lecia V.;Glisson, Bonnie S.;Khuri, Fadlo R.;Garon, Edward B.;Pao, William;Rudin, Charles;Schiller, Joan;Haura, Eric B.;Socinski, Mark;Shirai, Keisuke;Chen, Heidi;Giaccone, Giuseppe;Ladanyi, Marc;Kugler, Kelly;Minna, John D.;Bunn, Paul A.
通讯作者：
Bunn, Paul A.