Hu Kai, Yu Huomei, Liu Shiyan, Liao Deyu, Zhang Yan
Key Laboratory of Diagnostic Medicine of the Chinese Ministry of Education, School of Clinical Diagnostic and Laboratory Medicine, Chongqing Medical University, Chongqing, Yuzhong, China.
Front Mol Biosci. 2022 Sep 6;9:946507. doi: 10.3389/fmolb.2022.946507. eCollection 2022.
Regulator of chromatin condensation 1 (RCC1) is the major guanine nucleotide exchange factor of RAN GTPase, which plays a key role in various biological processes such as cell cycle and DNA damage repair. Small nucleolar RNA host gene 3 (SNHG3) and small nucleolar RNA host gene12 are long-stranded non-coding RNAs (lncRNAs) and are located on chromatin very close to the sequence of Regulator of chromatin condensation 1. Many studies have shown that they are aberrantly expressed in tumor tissues and can affect the proliferation and viability of cancer cells. Although the effects of Regulator of chromatin condensation 1/small nucleolar RNA host gene 3/small nucleolar RNA host gene12 on cellular activity have been reported, respectively, their overall analysis on the pan-cancer level has not been performed. Here, we performed a comprehensive analysis of Regulator of chromatin condensation 1/small nucleolar RNA host gene 3/small nucleolar RNA host gene12 in 33 cancers through the Cancer Genome Atlas and Gene Expression Database. The results showed that Regulator of chromatin condensation 1/small nucleolar RNA host gene 3/small nucleolar RNA host gene12 were highly expressed in a variety of tumor tissues compared to normal tissues. The expression of Regulator of chromatin condensation 1/small nucleolar RNA host gene 3/small nucleolar RNA host gene12 in BRCA, LGG and LIHC was associated with TP53 mutations. In addition, Regulator of chromatin condensation 1/small nucleolar RNA host gene 3/small nucleolar RNA host gene12 expression was closely associated with the prognosis of patients with multiple tumors. Immunocorrelation analysis indicated that Regulator of chromatin condensation 1/small nucleolar RNA host gene 3/small nucleolar RNA host gene12 showed a correlation with multiple immune cell infiltration. The results of enrichment analysis suggested that Regulator of chromatin condensation 1/small nucleolar RNA host gene 3/small nucleolar RNA host gene12 was involved in the regulation of cell cycle, apoptosis and other pathways. We found that these effects were mainly mediated by Regulator of chromatin condensation 1, while the trend of small nucleolar RNA host gene 3/small nucleolar RNA host gene12 regulation was also consistent with regulator of chromatin condensation 1. The important role played by Regulator of chromatin condensation 1 in tumor diseases was further corroborated by the study of adjacent lncRNAs.These findings provide new and comprehensive insights into the role of Regulator of chromatin condensation 1/small nucleolar RNA host gene 3/small nucleolar RNA host gene12 in tumor development and show their potential as clinical monitoring and therapy.
染色质凝聚调节因子1（RCC1）是RAN GTP酶的主要鸟嘌呤核苷酸交换因子，在细胞周期和DNA损伤修复等多种生物学过程中起关键作用。小核仁RNA宿主基因3（SNHG3）和小核仁RNA宿主基因12是长链非编码RNA（lncRNA），位于染色质上，与染色质凝聚调节因子1的序列非常接近。许多研究表明，它们在肿瘤组织中异常表达，可影响癌细胞的增殖和活力。虽然分别报道了染色质凝聚调节因子1/小核仁RNA宿主基因3/小核仁RNA宿主基因12对细胞活性的影响，但尚未在泛癌水平上对它们进行整体分析。在此，我们通过癌症基因组图谱和基因表达数据库对33种癌症中的染色质凝聚调节因子1/小核仁RNA宿主基因3/小核仁RNA宿主基因12进行了综合分析。结果显示，与正常组织相比，染色质凝聚调节因子1/小核仁RNA宿主基因3/小核仁RNA宿主基因12在多种肿瘤组织中高表达。染色质凝聚调节因子1/小核仁RNA宿主基因3/小核仁RNA宿主基因12在乳腺癌、低级别胶质瘤和肝细胞癌中的表达与TP53突变有关。此外，染色质凝聚调节因子1/小核仁RNA宿主基因3/小核仁RNA宿主基因12的表达与多种肿瘤患者的预后密切相关。免疫相关性分析表明，染色质凝聚调节因子1/小核仁RNA宿主基因3/小核仁RNA宿主基因12与多种免疫细胞浸润相关。富集分析结果表明，染色质凝聚调节因子1/小核仁RNA宿主基因3/小核仁RNA宿主基因12参与细胞周期、凋亡等途径的调控。我们发现这些作用主要由染色质凝聚调节因子1介导，而小核仁RNA宿主基因3/小核仁RNA宿主基因12的调控趋势也与染色质凝聚调节因子1一致。对相邻lncRNA的研究进一步证实了染色质凝聚调节因子1在肿瘤疾病中所起的重要作用。这些发现为染色质凝聚调节因子1/小核仁RNA宿主基因3/小核仁RNA宿主基因12在肿瘤发生发展中的作用提供了新的全面见解，并显示出它们作为临床监测和治疗手段的潜力。
