miR-3065-3p promotes stemness and metastasis by targeting CRLF1 in colorectal cancer

作者：Yifan Li, Jing Xun, Botao Wang, Yuan Ma, Lanqiu Zhang, Lei Yang, Ruifang Gao, Jun Guan, Tianyu Liu, Hejun Gao, Xi-Mo Wang, Qi Zhang · 发表于：Journal of Translational Medicine · 年份：2021 · DOI：10.1186/s12967-021-03102-y · 被引用次数：29 · 研究领域：MicroRNA in disease regulation、Circular RNAs in diseases、Cancer Cells and Metastasis

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 asses...