Oncogenic long intervening noncoding RNA Linc00284 promotes c-Met expression by sponging miR-27a in colorectal cancer.
Oncogenic long intervening noncoding RNA Linc00284 promotes c-Met expression by sponging miR-27a in colorectal cancer.
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致癌长干预非编码 RNA Linc00284 通过海绵 miR-27a 在结直肠癌中促进 c-Met 表达
DOI：
10.1038/s41388-021-01839-w
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发表时间：
2021-06
期刊：
影响因子：
8
通讯作者：
Li Q
中科院分区：
文献类型：
--
作者：
You J;Li J;Ke C;Xiao Y;Lu C;Huang F;Mi Y;Xia R;Li Q
越来越多的证据表明，长非编码RNA(LncRNA)在肿瘤的发生和发展中起着至关重要的作用。本研究旨在探讨Linc00284在结直肠癌中的生物学功能。用定量聚合酶链式反应和/或Western blotting检测Linc00284、miR-27A和c-Met的表达水平。免疫组织化学方法检测肿瘤组织中Ki67和Phh3的表达。通过荧光素酶报告实验和RNA免疫沉淀(RIP)实验验证Linc00284、miR-27A和c-Met之间的相互作用。进行细胞功能实验，包括CCK-8、伤口愈合和跨孔侵袭实验。采用皮下移植瘤小鼠模型进行体内研究。我们的结果表明，Linc00284在结直肠癌组织和结直肠癌细胞系HCT116和SW480中表达上调，而相应的癌旁组织和人胎儿结肠黏膜细胞FHC中Linc00284表达上调。Linc00284在肿瘤组织中的高表达与肿瘤转移有关，并预示着结直肠癌患者的临床预后不良。与健康对照组相比，结直肠癌患者血清Linc00284升高，miR-27A降低。ROC曲线分析表明，结直肠癌患者血清Linc00284和miR-27A产生的曲线下面积(AUC值)分别为0.8151和0.7316。此外，体外和体内实验结果表明，Linc00284沉默显著抑制了CRC细胞的增殖和/或侵袭。在机制上，Linc00284通过作为miR-27A海绵促进c-Met的表达，导致下游信号通路的激活，从而导致大肠癌细胞的恶性表型。综上所述，Linc00284具有致癌作用，Linc00284/miR-27A/c-Met调节轴的紊乱参与了结直肠癌的进展，为研究结直肠癌的发病机制提供了新的视角。重要的是，血清Linc00284和miR-27A的表达水平可作为临床诊断结直肠癌的生物标志物。
Emerging evidences suggest that long noncoding RNA (lncRNA) plays a vital role in tumorigenesis and cancer progression. Here, the aim of this study is to investigate the biological function of long intervening noncoding RNA Linc00284 in colorectal cancer (CRC). The expression levels of Linc00284, miR-27a and c-Met were evaluated by qPCR and/or Western blotting. Immunohistochemistry was used to detect the expression of Ki67 and Phh3 in tumor tissues. The interaction between Linc00284, miR-27a and c-Met was validated by luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Cell function experiments, including CCK-8, wound-healing and transwell invasion assays, were conducted. The in vivo studies were performed with the subcutaneous tumor xenograft mouse models. Our findings reveal that Linc00284 is upregulated in CRC tissues and colorectal cancer cell lines HCT116 and SW480 in comparison with corresponding para-carcinoma tissues and human fetal colonic mucosa cells FHC. High expression of Linc00284 in tumor tissues is associated with tumor metastasis and predicts a poor clinical outcome in CRC patients. Serum Linc00284 is increased, while miR-27a is decreased in CRC patients compared to healthy controls. ROC curve analysis indicates that serum Linc00284 and miR-27a produce the area under the curve (AUC) value of at 0.8151 and 0.7316 in patients with colorectal cancer compared to healthy individuals, respectively. Additionally, results in vitro and in vivo experiments suggest that Linc00284 silencing significantly suppresses CRC cell proliferation and/or invasion. Mechanistically, Linc00284 promotes c-Met expression by acting as miR-27a sponge, leading to the activation of downstream signaling pathways, thereby causing malignant phenotypes of CRC cells. Taken together, Linc00284 exhibits oncogenic function and the disturbance of Linc00284/miR-27a/c-Met regulatory axis contributes to CRC progression, providing new insight into the pathogenesis of colorectal cancer. Importantly, the expression levels of serum Linc00284 and miR-27a may serve as clinical biomarkers for CRC diagnosis.
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