Yang Yang, Zhao Yanan, Zhang Wenlong, Bai Yuansong
Department of Oncology and Hematology, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, People's Republic of China,
Onco Targets Ther. 2019 Apr 10;12:2737-2747. doi: 10.2147/OTT.S195235. eCollection 2019.
This study aimed to investigate the key long non-coding RNAs (lncRNAs) associated with colon cancer and elucidate their possible mechanisms of action.
Eight early-stage (ES) colon tumor tissues, eight late-stage (LS) colon tumor tissues, and eight normal tissues were collected, and they were subjected to high-throughput RNA sequencing. Subsequently, comprehensive bioinformatics analyses, including the identification of differentially expressed mRNAs and lncRNAs, functional enrichment analysis, and construction of a protein-protein interaction network and an miRNA-lncRNA-mRNA regulatory network were performed. Additionally, the expression of key lncRNAs was verified using real-time quantitative PCR (qPCR).
In total, 549 common differentially expressed mRNAs and 30 common differentially expressed lncRNAs were identified in both the ES and LS colon cancer samples upon comparison with the normal samples. Functional enrichment analysis showed that KIAA0125 was significantly enriched in the PI3K-Akt signaling pathway and that MSTRG.35002.1 was markedly enriched in BMP signaling-related functions. Moreover, key miRNA-lncRNA-mRNA relationships, such as hsa-miR-29b-3p-KIAA0125-BCL2 and hsa-miR-29b-3p-MSTRG.35002.1-MMP2, were identified. Notably, the qPCR assay confirmed that KIAA0125 and MSTRG.35002.1 were significantly downregulated in both ES and LS colon tumor tissues compared with normal colon tissues.
Our findings indicate that key lncRNAs, including KIAA0125 and MSTRG.35002.1, may be involved in colorectal cancer (CRC) development. Downregulation of KIAA0125 may contribute to CRC development via sponging of hsa-miR-29b-3p to regulate BCL2 expression or regulating the PI3K-Akt signaling pathway. Downregulation of MSTRG.35002.1 may promote CRC development via sponging of hsa-miR-29b-3p to regulate MMP2 expression or regulating the BMP signaling pathway.
本研究旨在探究与结肠癌相关的关键长链非编码RNA（lncRNA），并阐明其可能的作用机制。
收集8例早期（ES）结肠癌组织、8例晚期（LS）结肠癌组织和8例正常组织，并进行高通量RNA测序。随后，进行了全面的生物信息学分析，包括差异表达的mRNA和lncRNA的鉴定、功能富集分析以及蛋白质-蛋白质相互作用网络和miRNA-lncRNA-mRNA调控网络的构建。此外，使用实时定量PCR（qPCR）验证关键lncRNA的表达。
与正常样本相比，在ES和LS结肠癌样本中总共鉴定出549个常见的差异表达mRNA和30个常见的差异表达lncRNA。功能富集分析表明，KIAA0125在PI3K-Akt信号通路中显著富集，而MSTRG.35002.1在与BMP信号相关的功能中显著富集。此外，还鉴定出关键的miRNA-lncRNA-mRNA关系，如hsa-miR-29b-3p-KIAA0125-BCL2和hsa-miR-29b-3p-MSTRG.35002.1-MMP2。值得注意的是，qPCR检测证实，与正常结肠组织相比，KIAA0125和MSTRG.35002.1在ES和LS结肠癌组织中均显著下调。
我们的研究结果表明，包括KIAA0125和MSTRG.35002.1在内的关键lncRNA可能参与结直肠癌（CRC）的发生发展。KIAA0125的下调可能通过吸附hsa-miR-29b-3p来调节BCL2表达或调节PI3K-Akt信号通路，从而促进CRC的发生发展。MSTRG.35002.1的下调可能通过吸附hsa-miR-29b-3p来调节MMP2表达或调节BMP信号通路，从而促进CRC的发生发展。
