School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Cas Key Laboratory of Bio-medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, China.
Bioengineered. 2021 Dec;12(2):9473-9483. doi: 10.1080/21655979.2021.1995574.
-methyladenosine (mA) has been involved in diverse biological processes in cancer, but its function and clinical value in clear cell renal cell carcinoma (ccRCC) remain largely unknown. In this study, we found that 1453 mA-modified differentially expressed genes (DEGs) of ccRCC were mainly enriched in cell cycle, PI3K-AKT, and p53 signaling pathways. Then we constructed a co-expression network of the 1453 mA-modified DEGs and identified a most clinically relevant module, where NUF2, CDCA3, CKAP2L, KIF14, and ASPM were hub genes. NUF2, CDCA3, and KIF14 could combine with a major RNA mA methyltransferase METTL14, serving as biomarkers for ccRCC. Real-time quantitative PCR assay confirmed that NUF2, CDCA3, and KIF14 were highly expressed in ccRCC cell lines and ccRCC tissues. Furthermore, these three genes were modified by mA and negatively regulated by METTL14. This study revealed that NUF2, CDCA3, and KIF14 were mA-modified biomarkers, representing a potential diagnostic, prognostic, and therapeutic target for ccRCC. mA: -methyladenosine; ccRCC: clear cell renal cell carcinoma; DEGs: differentially expressed genes; NUF2: NUF2 component of NDC80 kinetochore complex; CDCA3: cell division cycle associated 3; CKAP2L: cytoskeleton associated protein 2 like; KIF14: kinesin family member 14; ASPM: assembly factor for spindle microtubules; METTL14: methyltransferase 14; OS: overall survival; FPKM: fragments per kilobase million; GEO: gene expression omnibus; TCGA: the Cancer Genome Atlas; RMA: robust multi-array average expression measure; WGCNA: weighted gene co-expression network analysis; GO: gene ontology; KEGG: kyoto encyclopedia of genes and genomes; ROC: receiver operating characteristic curve; AUC: area under the curve; RIP: RNA immunoprecipitation; qPCR: real-time quantitative PCR.
m6A 修饰在癌症的多种生物学过程中发挥作用，但在透明细胞肾细胞癌（ccRCC）中的功能和临床价值仍知之甚少。在本研究中，我们发现 1453 个 m6A 修饰的 ccRCC 差异表达基因（DEGs）主要富集在细胞周期、PI3K-AKT 和 p53 信号通路中。然后，我们构建了 1453 个 m6A 修饰的 DEGs 的共表达网络，并确定了一个最具临床相关性的模块，其中 NUF2、CDCA3、CKAP2L、KIF14 和 ASPM 是枢纽基因。NUF2、CDCA3 和 KIF14 可以与主要的 RNA m6A 甲基转移酶 METTL14 结合，作为 ccRCC 的生物标志物。实时定量 PCR 检测证实，NUF2、CDCA3 和 KIF14 在 ccRCC 细胞系和 ccRCC 组织中高表达。此外，这三个基因均被 m6A 修饰，并受到 METTL14 的负调控。本研究表明，NUF2、CDCA3 和 KIF14 是 m6A 修饰的生物标志物，代表了 ccRCC 的潜在诊断、预后和治疗靶点。
