miR-3065-3p 通过靶向 CRLF1 促进结直肠癌的干性和转移。
miR-3065-3p promotes stemness and metastasis by targeting CRLF1 in colorectal cancer.
机构信息
Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin, China.
Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and Integrated Chinese and Western Medicine (ITCWM) Repair, Institute of Integrative Medicine for Acute Abdominal Diseases, Integrated Chinese and Western Medicine Hospital, Tianjin University, Tianjin, China.
出版信息
J Transl Med. 2021 Oct 16;19(1):429. doi: 10.1186/s12967-021-03102-y.
BACKGROUND
Colorectal cancer is one of the most common malignancy in the world. It has been reported that cancer stem cells (CSCs) serve as the primary drivers of tumorigenesis and tumor progression. There is an urgent need to explore novel molecules that regulate CSCs or their signatures. Increasing evidence has shown that miRNAs are involved in tumorigenesis and progression. Here, we aim to explore the regulatory effect and mechanism of miR-3065-3p on the stemness of colorectal cancer.
METHODS
The expression of miR-3065-3p in colorectal cancer and the association of miR-3065-3p expression with prognosis of patients with colorectal cancer were analyzed using TCGA dataset or clinical cases. Gain or loss of function in different models, including colorectal cancer cell lines and orthotopic xenograft or liver metastatic mouse model, were used to investigate the effects of miR-3065-3p on colorectal cancer stemness and metastasis in vitro and in vivo. Cancer stemness was analyzed by detecting the ability of migration and invasion, NANOG, OCT4, and SOX2 expression, ALDH activity and sphere formation. In addition, the interaction of miR-3065-3p and cytokine receptor-like factor 1 (CRLF1) was analyzed theoretically and identified by the luciferase reporter assay. Moreover, the correlation between CRLF1 expression and miR-3065-3p was analyzed in colorectal cancer tissues. Finally, the effect of CRLF1 on the stemness and metastasis of colorectal cancer in vitro and in vivo was assessed.
RESULTS
In this report, we found that miR-3065-3p was overexpressed in colorectal cancer and that its high expression was associated with poor prognosis of patients with colorectal cancer. miR-3065-3p promotes the stemness and metastasis of colorectal cancer. Furthermore, CRLF1 was the downstream target of miR-3065-3p and inhibited the stemness of colorectal cancer. In addition, CRLF1 expression was negatively correlated with miR-3065-3p in colorectal cancer tissues. And, CRLF1 mediated the effects of miR-3065-3p on promoting stemness of colorectal cancer cells.
CONCLUSION
Our data suggest that miR-3065-3p promoted the stemness and metastasis of colorectal cancer by targeting CRLF1. miR-3065-3p might serve as a promising prognostic marker as well as a therapeutic target for colorectal cancer.
背景
结直肠癌是世界上最常见的恶性肿瘤之一。据报道，癌症干细胞（CSCs）是肿瘤发生和肿瘤进展的主要驱动因素。因此，迫切需要探索调节 CSCs 或其特征的新型分子。越来越多的证据表明，miRNA 参与了肿瘤的发生和发展。在这里，我们旨在探索 miR-3065-3p 对结直肠癌细胞干性的调节作用和机制。
方法
使用 TCGA 数据集或临床病例分析结直肠癌中 miR-3065-3p 的表达情况，以及 miR-3065-3p 表达与结直肠癌患者预后的关系。在不同模型中（包括结直肠癌细胞系和原位异种移植或肝转移小鼠模型），通过获得或丧失功能，研究 miR-3065-3p 对结直肠癌细胞干性和转移的影响，在体外和体内。通过检测迁移和侵袭能力、NANOG、OCT4 和 SOX2 表达、ALDH 活性和球体形成，分析癌症干性。此外，通过理论分析和荧光素酶报告基因检测鉴定 miR-3065-3p 与细胞因子受体样因子 1（CRLF1）的相互作用。此外，分析结直肠癌组织中 CRLF1 表达与 miR-3065-3p 的相关性。最后，评估 CRLF1 对结直肠癌细胞干性和转移的体内外影响。
结果
在本报告中，我们发现 miR-3065-3p 在结直肠癌中高表达，并且其高表达与结直肠癌患者的不良预后相关。miR-3065-3p 促进结直肠癌细胞的干性和转移。此外，CRLF1 是 miR-3065-3p 的下游靶标，并抑制结直肠癌细胞的干性。此外，结直肠癌组织中 CRLF1 表达与 miR-3065-3p 呈负相关。并且，CRLF1 介导了 miR-3065-3p 促进结直肠癌细胞干性的作用。
结论
我们的数据表明，miR-3065-3p 通过靶向 CRLF1 促进结直肠癌细胞的干性和转移。miR-3065-3p 可能作为结直肠癌有前途的预后标志物和治疗靶点。
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