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整合生物信息学和实验分析表明,下调的CDC42EP3是卵巢癌的一种新的预后靶点及其在免疫浸润中的作用。

Integrative bioinformatics and experimental analysis revealed down-regulated CDC42EP3 as a novel prognostic target for ovarian cancer and its roles in immune infiltration.

作者信息

Yan Yuanliang, Liang Qiuju, Xu Zhijie, Yi Qiaoli

机构信息

Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, Hunan, China.

Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan, China.

出版信息

PeerJ. 2021 Sep 15;9:e12171. doi: 10.7717/peerj.12171. eCollection 2021.

Abstract

Ovarian cancer is a significant clinical challenge as no effective treatments are available to enhance patient survival. Recently, N6-methyladenosine (mA) RNA modification has been demonstrated to play a pivotal role in tumorigenesis and progression. However, the roles of mA target genes in ovarian cancer haven't been clearly illustrated. In this study, we presented a comprehensive bioinformatics and in vitro analysis to evaluate the roles of mA target genes. Cell division cycle 42 effector protein 3 (CDC42EP3), one probable m6A target gene, was identified to be down-regulated in ovarian cancer tissues and cells. Meanwhile, quantitative PCR (qPCR) and western blot were used to confirm the down-regulated CDC42EP3 in ovarian cancer cells A2780 and TOV112D. The biological function of CDC42EP3 in ovarian cancer was further validated with several algorithms, such as PrognoScan, K-M plotter, LinkedOmics and TISIDB. These findings indicated that lower expression of CDC42EP3 was correlated with poor prognosis in patients with ovarian cancer. In addition, CDC42EP3 expression was significantly associated with a diverse range of tumor-infiltrating immune cells, including natural killer cells (NK), T central memory cells (Tcm), T gamma delta cells (Tgd), etc. Taken together, this study uncovered the potential roles of mA target gene CDC42EP3 in the regulation of immune microenvironment in the ovarian cancer, and identified CDC42EP3 as a novel prognostic target.

摘要

卵巢癌是一项重大的临床挑战,因为目前尚无有效的治疗方法来提高患者生存率。最近,N6-甲基腺苷(m⁶A)RNA修饰已被证明在肿瘤发生和进展中起关键作用。然而,m⁶A靶基因在卵巢癌中的作用尚未得到明确阐明。在本研究中,我们进行了全面的生物信息学和体外分析,以评估m⁶A靶基因的作用。细胞分裂周期42效应蛋白3(CDC42EP3)是一个可能的m⁶A靶基因,被发现在卵巢癌组织和细胞中表达下调。同时,使用定量PCR(qPCR)和蛋白质免疫印迹法来证实卵巢癌细胞A2780和TOV112D中CDC42EP3的表达下调。通过PrognoScan、K-M plotter、LinkedOmics和TISIDB等多种算法进一步验证了CDC42EP3在卵巢癌中的生物学功能。这些发现表明,CDC42EP3表达降低与卵巢癌患者的不良预后相关。此外,CDC42EP3表达与多种肿瘤浸润免疫细胞显著相关,包括自然杀伤细胞(NK)、T中央记忆细胞(Tcm)、Tγδ细胞(Tgd)等。综上所述,本研究揭示了m⁶A靶基因CDC42EP3在卵巢癌免疫微环境调节中的潜在作用,并将CDC42EP3确定为一个新的预后靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd25/8449529/239de5d754d2/peerj-09-12171-g001.jpg

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