Medical Biochemistry Department, Faculty of Medicine,Tanta University, Tanta, Egypt.
Histopathology Depatment, Faculty of medicine, Tanta University, Tanta, Egypt.
Mol Biol Rep. 2019 Feb;46(1):657-667. doi: 10.1007/s11033-018-4521-0. Epub 2018 Nov 27.
Colorectal cancer (CRC) is among the leading causes of cancer-related mortality worldwide. Compelling evidence suggests that long non-coding RNA (lncRNAs) can control carcinogenesis by regulating various aspects of cell biology. However, limited number of CRC-related lncRNAs has been well characterized. This study was undertaken to investigate the expression pattern of the novel lncRNA-CCHE1 in CRC patients and to examine its correlation with clinicopathological features, ERK/COX-2 pathway and some cell proliferation markers in order to gain biological insights on its role in CRC pathogenesis. Colon cancer specimens with their adjacent non-cancerous tissues were taken from 60 patients with primary CRC. LncRNA-CCHE1 relative expression was assessed using quantitative real-time RT-PCR. P-ERK ½ and cyclin D1 levels were estimated by ELISA. COX-2 and proliferating cell nuclear antigen (PCNA) expression were assessed immunohistochemically. lncRNA-CCHE1 expression was upregulated in CRC tissues compared to adjacent non-cancerous tissues, and was significantly associated with larger tumor size, less differentiated histology, advanced dukes' stage, positive lymph node involvement and vascular invasion. It also showed a significant positive correlation with the expression of p-ERK1/2, COX-2 as well as cyclin D1and PCNA (as markers for cell proliferation). These findings signify that lncRNA-CCHE1 is a key oncogene possibly involved in CRC development and progression by modulating ERK/COX-2 pathway and cell proliferation activity. Our study also provides a rationale for potential use of lncRNA-CCHE1 as a novel prognostic marker, and opens the door for the development of lncRNA-CCHE1-directed therapeutic approaches for CRC patients.
结直肠癌(CRC)是全球癌症相关死亡率的主要原因之一。有强有力的证据表明,长链非编码 RNA(lncRNA)可以通过调节细胞生物学的各个方面来控制癌变。然而,具有明确特征的 CRC 相关 lncRNA 的数量有限。本研究旨在调查新型 lncRNA-CCHE1 在 CRC 患者中的表达模式,并研究其与临床病理特征、ERK/COX-2 通路和一些细胞增殖标志物的相关性,以深入了解其在 CRC 发病机制中的作用。从 60 名原发性 CRC 患者的结肠癌标本及其相邻非癌组织中获取 lncRNA-CCHE1 相对表达量,采用实时定量 RT-PCR 进行评估。通过 ELISA 估计 P-ERK ½和细胞周期蛋白 D1 水平。通过免疫组化评估 COX-2 和增殖细胞核抗原(PCNA)的表达。与相邻非癌组织相比,CRC 组织中 lncRNA-CCHE1 的表达上调,且与肿瘤较大、组织分化较差、 Dukes 分期较晚、淋巴结阳性转移和血管侵犯有关。它还与 p-ERK1/2、COX-2 以及细胞周期蛋白 D1和 PCNA(作为细胞增殖的标志物)的表达呈显著正相关。这些发现表明,lncRNA-CCHE1 是一种关键的癌基因,可能通过调节 ERK/COX-2 通路和细胞增殖活性,参与 CRC 的发生和发展。我们的研究还为将 lncRNA-CCHE1 作为一种新的预后标志物的潜在应用提供了依据,并为开发针对 CRC 患者的 lncRNA-CCHE1 靶向治疗方法开辟了道路。