Jiang Xiulin, Yuan Yixiao, Tang Lin, Wang Juan, Liu Qianqian, Zou Xiaolan, Duan Lincan
Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming, China.
Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming, China
Front Cell Dev Biol. 2021 Nov 10;9:765772. doi: 10.3389/fcell.2021.765772. eCollection 2021.
Growing evidence has demonstrated that UBE2C plays a critical role in cancer progression, but there is no study focusing on the prognosis, upstream regulation mechanism, and immunological roles of UBE2C across diverse tumor types. In this study, we found that UBE2C was elevated in this human pan-cancer analysis, and high expression of UBE2C was correlated with poor prognosis. In addition, UBE2C expression was markedly associated with tumor mutation burden (TMB), microsatellite instability (MSI), immune cell infiltration, and diverse drug sensitivities. Finally, we showed that the METTL3/SNHG1/miRNA-140-3p axis could potentially regulate UBE2C expression. N(6)-Methyladenosine (m6A) modifications improved the stability of methylated SNHG1 transcripts by decreasing the rate of RNA degradation, which lead to upregulation of SNHG1 in non-small cell lung cancer (NSCLC). functional experiments showed that SNHG1, as a competing endogenous RNA, sponges miR-140-3p to increase UBE2C expression in NSCLC cell lines. Our study elucidates the clinical importance and regulatory mechanism of the METTL3/SNHG1/miRNA-140-3p/UBE2C axis in NSCLC and provides a prognostic indicator, as well as a promising therapeutic target for patients with NSCLC.
越来越多的证据表明,UBE2C在癌症进展中起着关键作用,但尚无针对UBE2C在不同肿瘤类型中的预后、上游调控机制及免疫作用的研究。在本研究中,我们发现在这项泛癌分析中UBE2C水平升高,且UBE2C高表达与预后不良相关。此外,UBE2C表达与肿瘤突变负荷(TMB)、微卫星不稳定性(MSI)、免疫细胞浸润及多种药物敏感性显著相关。最后,我们表明METTL3/SNHG1/miRNA-140-3p轴可能调控UBE2C表达。N6-甲基腺苷(m6A)修饰通过降低RNA降解速率提高了甲基化SNHG1转录本的稳定性,导致非小细胞肺癌(NSCLC)中SNHG1上调。功能实验表明,SNHG1作为一种竞争性内源RNA,在NSCLC细胞系中通过吸附miR-140-3p来增加UBE2C表达。我们的研究阐明了METTL3/SNHG1/miRNA-140-3p/UBE2C轴在NSCLC中的临床重要性和调控机制,并为NSCLC患者提供了一个预后指标以及一个有前景的治疗靶点。