Department of Biology, Azad University, Ashkezar Branch, Yazd, Iran.
Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, Devon, UK.
Int J Exp Pathol. 2023 Jun;104(3):107-116. doi: 10.1111/iep.12467. Epub 2023 Feb 2.
Incomplete knowledge of the molecular basis of colorectal cancer, with subsequent limitations in early diagnosis and effective treatment, has contributed to this form of malignancy becoming the second most common cause of cancer-related death worldwide. With the advances in high-throughput profiling techniques and the availability of public data sets such as The Cancer Genome Atlas Program (TCGA), a broad range of coding transcripts have been profiled and their underlying modes of action have been mapped. However, there is still a huge gap in our understanding of noncoding RNA dysregulation. To this end, we used a bioinformatics approach to shortlist and evaluate yet-to be-profiled long noncoding RNAs (lncRNAs) in colorectal cancer. We analysed the TCGA RNA-seq data and followed this by validating the expression patterns using a qPCR technique. Analysing in-house clinical samples, the real-time PCR method revealed that the shortlisted lncRNAs, that is MER1 Repeat Containing Imprinted Transcript 1 (MIMT1) and Non-Protein Coding RNA 1550 (LINC01550), were down-regulated in colorectal cancer tumours compared with the paired adjacent normal tissues. Mechanistically, the in silico results suggest that LINC01550 could form a complex competitive endogenous RNA (ceRNA) network leading to the subsequent regulation of colorectal cancer-related genes, such as CUGBP Elav-Like Family Member (CELF2), Polypyrimidine Tract Binding Protein 1 (PTBP1) and ELAV Like RNA Binding Protein 1 (ELAV1). The findings of this work indicate that MIMT1 and LINC01550 could be novel tumour suppressor genes that can be studied further to assess their roles in regulating the cancer signalling pathway(s).
对结直肠癌分子基础的不完全了解，继而导致早期诊断和有效治疗受到限制，这使得这种恶性肿瘤成为全球癌症相关死亡的第二大常见原因。随着高通量分析技术的进步和公共数据集（如癌症基因组图谱计划（TCGA））的出现，广泛的编码转录本已经被分析，其潜在的作用模式也已经被绘制出来。然而，我们对非编码 RNA 失调的理解仍然存在很大的差距。为此，我们使用生物信息学方法来筛选和评估结直肠癌中尚未进行分析的长链非编码 RNA（lncRNA）。我们分析了 TCGA 的 RNA-seq 数据，然后使用 qPCR 技术验证表达模式。通过分析内部临床样本，实时 PCR 方法显示，在所筛选的 lncRNA 中，即 MER1 重复内含子转录物 1（MIMT1）和非蛋白编码 RNA1550（LINC01550），在结直肠癌肿瘤中与配对的相邻正常组织相比表达下调。从机制上讲，计算机模拟结果表明，LINC01550 可能形成一个复杂的竞争性内源 RNA（ceRNA）网络，从而导致结直肠癌相关基因的后续调节，如 CUGBP 埃拉样家族成员（CELF2）、多嘧啶 tract 结合蛋白 1（PTBP1）和埃拉样 RNA 结合蛋白 1（ELAV1）。这项工作的结果表明，MIMT1 和 LINC01550 可能是新的肿瘤抑制基因，可以进一步研究它们在调节癌症信号通路中的作用。
