Biotechnology Graduate Program, American University in Cairo, New Cairo, Egypt.
Department of Chemistry and American University in Cairo, New Cairo, Egypt.
OMICS. 2021 May;25(5):302-312. doi: 10.1089/omi.2020.0231. Epub 2021 Apr 22.
Colorectal cancer (CRC) is the third leading cause of death worldwide, comprising nearly 8% of cancer-related deaths per year. In South Korea, for example, CRC is the second most common cancer in men, and third in women. This study reports on the association of CRC with genetic variations in long noncoding RNAs, activators, and inhibitors of a cell proliferation pathway. Five normal colon mucosa tissue samples and their matched five-stage IV CRC samples were evaluated (dataset Gene Expression Omnibus accession: GSE50760). We identified more than 5000 differentially expressed genes (DEGs). The Wnt pathway had the greatest portion of DEGs, including activators, inhibitors, and associated long noncoding RNAs (lncRNAs), suggesting the importance of Wnt pathway in CRC. The following genes were aberrantly expressed: , , , , , , , , and . Notably, is known to silence , and inhibits the Wnt ligands to negatively regulate the pathway. The lncRNA positively regulates , while positively regulates and . We note that HOTAIR was unable to silence . and were found to be upregulated, which may explain the high expression of the targets. Furthermore, 10 single-nucleotide polymorphisms (SNPs) were identified in five of the candidate genes above. A possible novel SNP in , chr11:44619242T > C, was predicted to introduce a binding site. These SNPs are hypothesized to contribute to aberrant and discrepant regulation of the Wnt pathway in a context of CRC pathogenesis. These findings collectively inform future research on diagnostics and therapeutics innovation in CRC.
结直肠癌（CRC）是全球第三大死亡原因，每年约占癌症相关死亡人数的 8%。例如，在韩国，CRC 在男性中是第二常见的癌症，在女性中是第三常见的癌症。本研究报告了结直肠癌与细胞增殖途径的长非编码 RNA、激活剂和抑制剂的遗传变异之间的关联。评估了 5 个正常结肠黏膜组织样本及其匹配的 5 期 IV 期 CRC 样本（数据集基因表达综合数据库访问号：GSE50760）。我们鉴定出 5000 多个差异表达基因（DEGs）。Wnt 途径具有最大比例的 DEGs，包括激活剂、抑制剂和相关的长非编码 RNA（lncRNA），表明 Wnt 途径在 CRC 中的重要性。以下基因表达异常：、、、、、、、和。值得注意的是，已知沉默，而抑制 Wnt 配体以负调控该途径。lncRNA 正向调节，而正向调节和。我们注意到 HOTAIR 无法沉默。和被发现上调，这可能解释了靶基因的高表达。此外，在上述五个候选基因中鉴定出 10 个单核苷酸多态性（SNP）。在候选基因中的一个可能的新 SNP，chr11:44619242T > C，预测会引入一个 结合位点。这些 SNP 假设导致 Wnt 途径在 CRC 发病机制中的异常和差异调节。这些发现共同为 CRC 的诊断和治疗创新的未来研究提供了信息。
