Genetic Department, University of Medical Sciences, Ganjafrooz Street, Babol, Mazandaran, Iran.
Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan, Iran.
BMC Cancer. 2023 Jan 9;23(1):34. doi: 10.1186/s12885-022-10464-z.
All cell types express long non-coding RNAs (lncRNAs), which have the potential to play a role in carcinogenesis by altering the levels of their expression. Squamous cell carcinoma of the esophagus (ESCC) is a deadly disease with a poor prognosis and a high frequency of lymphatic metastases. Understanding the functional role and signaling pathways of two neighboring lncRNAs, CCAT1 and PVT1, in this oncogene's pathogenesis may help us determine ESCC. Furthermore, it is still unclear whether these lncRNAs are linked to the clinicopathological characteristics of patients with ESCC.
For this study, we used biopsy from the Imam Khomeini Cancer Institute's tumor bank in Tehran, Iran to obtain 40 ESCC tumor samples and their normal margin counterparts. The expression levels of the CCAT1, PVT1, and c-MYC genes were assessed using quantitative Real-Time RT-PCR. Additionally, demographic data and clinical-pathologic characteristics, such as tumor grade, tumor stage, lymph node, and metastasis, were taken into consideration. Graphpad prism version 8 was used for bioinformatics analyses.
Comparing ESCC tissues to non-tumor tissues, we found significant upregulation of PVT1, CCAT1, and c-MYC. Patients with ESCC who had increased PVT1 expression also had higher rates of advanced stage and lymph node metastasis, whereas increased CCAT1 expression was only linked to advanced stage and wasn't associated with lymph node metastasis. In predicting ESCC, CCAT1 (p < 0.05) was found to be an important factor. Overall survival was reduced by c-MYC and PVT1 overexpression (p < 0.001), according to Kaplan-Meier analysis. PVT1, CCAT1, and c-MYC were found to interact with 23 miRNAs with high and medium score classes, as shown in a bioinformatics study. We summarized the experimentally proven interactions between c-MYC, PVT1, and CCAT1 and other miRNAs, lncRNAs, and proteins.
This is the first report that CCAT1, PVT1 and c-MYC have been found to be up-regulated simultaneously in ESCC. It is possible that these genes may be involved in ESCC as a result of these findings. Therefore, as consequence, more research is needed to determine whether or not these lncRNAs play an oncogenic role in ESCC development and progression, as well as the regulatory mechanisms that control them.
所有细胞类型都表达长非编码 RNA（lncRNA），这些 RNA 有可能通过改变其表达水平在致癌作用中发挥作用。食管鳞状细胞癌（ESCC）是一种预后不良且淋巴转移频率较高的致命疾病。了解两个相邻 lncRNA，CCAT1 和 PVT1 在这个癌基因发病机制中的功能作用和信号通路，可能有助于我们确定 ESCC。此外，这些 lncRNA 是否与 ESCC 患者的临床病理特征有关仍不清楚。
在这项研究中，我们使用来自伊朗德黑兰伊玛目霍梅尼癌症研究所肿瘤库的活检组织获得了 40 例 ESCC 肿瘤样本及其正常边缘对照。使用定量实时 RT-PCR 评估 CCAT1、PVT1 和 c-MYC 基因的表达水平。此外，还考虑了人口统计学数据和临床病理特征，如肿瘤分级、肿瘤分期、淋巴结和转移。使用 Graphpad prism 版本 8 进行生物信息学分析。
与非肿瘤组织相比，我们发现 ESCC 组织中 PVT1、CCAT1 和 c-MYC 的表达显著上调。PVT1 表达增加的 ESCC 患者也具有较高的晚期分期和淋巴结转移率，而 CCAT1 表达增加仅与晚期分期相关，与淋巴结转移无关。在预测 ESCC 时，发现 CCAT1（p<0.05）是一个重要因素。根据 Kaplan-Meier 分析，c-MYC 和 PVT1 的过表达降低了总生存率（p<0.001）。生物信息学研究表明，CCAT1、PVT1 和 c-MYC 与 23 个具有高和中评分类别的 miRNA 相互作用。我们总结了 c-MYC、PVT1 和 CCAT1 与其他 miRNA、lncRNA 和蛋白质之间的实验证实的相互作用。
这是第一项报道表明 CCAT1、PVT1 和 c-MYC 在 ESCC 中同时被发现上调。这些发现提示这些基因可能参与 ESCC。因此，有必要进一步研究这些 lncRNA 是否在 ESCC 发展和进展中发挥致癌作用，以及控制它们的调节机制。
