Despite improvements in prognosis due to advances in treatment, including surgery, genetic screening, and molecular targeted therapy, the outcomes of ovarian cancer (OC) remain unsatisfactory. Internal mRNA modifications are extremely common in eukaryotes; N6-methyladenosine (m6A) alteration has significant effects on mRNA stability and translation, and it is involved in the pathophysiology of numerous diseases related to cancer. Bioinformatics analysis, quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of vir-like m6A methyltransferase associated (KIAA1429) in OC tissues and cell lines. Several different cell models and animal models were established to determine the role of KIAA1429 in glucose metabolism reprogramming and the underlying molecular mechanism of OC. The mechanism of oncology functional assays, co-immunoprecipitation and a luciferase reporter gene was employed to ascertain how KIAA1429 interacts with important molecular targets. We reported that KIAA1429 was overexpressed in OC and predicted a poor prognosis. Functionally, KIAA1429 promoted cell growth by inducing proliferation and inhibiting necrosis. Mechanistically, KIAA1429 promoted tumor progression and glycolysis via stabilizing ENO1 mRNA in a way dependent on m6A. Furthermore, we investigated that the SPI1 transcription factor is the main transcription factor that regulates KIAA1429 transcription in OC. Our findings revealed that SPI1/KIAA1429/ENO1 signaling is a novel molecular axis and raises awareness of the vital functions of the changes in KIAA1429 and m6A changes in the metabolic reprogramming of OC. These results identified new potential biomarkers and treatment targets for OC.

中文翻译：

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N6-甲基腺苷甲基转移酶KIAA1429通过增强ENO1表达促进卵巢癌有氧糖酵解和进展

尽管手术、基因筛查和分子靶向治疗等治疗方法的进步改善了预后，但卵巢癌（OC）的治疗结果仍然不令人满意。内部 mRNA 修饰在真核生物中极其常见；N6-甲基腺苷 (m6A) 改变对 mRNA 稳定性和翻译具有显着影响，并且参与多种癌症相关疾病的病理生理学。采用生物信息学分析、实时定量聚合酶链反应和Western blotting检测OC组织和细胞系中vir样m6A甲基转移酶相关蛋白（KIAA1429）的表达。建立了几种不同的细胞模型和动物模型来确定 KIAA1429 在葡萄糖代谢重编程中的作用以及 OC 的潜在分子机制。采用肿瘤功能测定、免疫共沉淀和荧光素酶报告基因的机制来确定 KIAA1429 如何与重要的分子靶标相互作用。我们报道 KIAA1429 在 OC 中过度表达并预测预后不良。从功能上讲，KIAA1429 通过诱导增殖和抑制坏死来促进细胞生长。从机制上讲，KIAA1429 通过以依赖于 m6A 的方式稳定 ENO1 mRNA，促进肿瘤进展和糖酵解。此外，我们研究发现SPI1转录因子是OC中调节KIAA1429转录的主要转录因子。我们的研究结果表明，SPI1/KIAA1429/ENO1 信号传导是一种新型分子轴，提高了人们对 OC 代谢重编程中 KIAA1429 变化和 m6A 变化的重要功能的认识。这些结果确定了 OC 的新潜在生物标志物和治疗靶点。