This study aimed to investigate the role of circ0106714‐miR‐942‐5p‐discs large homolog 2 (DLG2), a novel interactome, in colorectal cancer (CRC). Circ0106714 was found to be the most significantly downregulated circular RNA in CRC using a bioinformatics method, and we researched whether the ability of circ0106714 to sponge miR‐942‐5p and release DLG2 could affect CRC development via Hippo‐YES‐associated protein (YAP) signaling. We first employed qRT‐PCR and immunoblotting to detect messenger RNA (mRNA) and protein expression, respectively. Live imaging of mice tumor xenografts was then conducted to study the effect of circ0106714 on tumor progression in vivo. Reporter gene assays were subsequently conducted to verify the predicted targeting relationship between circ0106714, miR‐942‐5p, and DLG2 mRNA in SW480 and HCT116 cell lines. As well as using flow cytometry for both apoptosis and cell cycle profile analyses, CCK‐8 and clone foci formation assays were performed to assess cell survival. Wound healing assay and transwell invasion assay were later carried out to evaluate the migration and invasion of the cell lines. Findings revealed that circ0106714 and DLG2 were significantly downregulated, while miR‐942‐5p was significantly upregulated in human CRC tissues and cell lines. However, circ0106714 upregulation significantly suppressed tumor progression in vivo and inhibited the malignancy phenotypes of tumor cells in vitro by targeting miR‐942‐5p. Also discovered in this research was that miR‐942‐5p could directly target DLG2 mRNA, thus enhancing the malignancy phenotypes of CRC cells. We even found that DLG2 overexpression resulted in enhanced phosphorylation of YAP, a critical downstream effector of DLG2. This downstream effector was demonstrated to have a tumor‐suppressive capacity in CRC cell lines. In sum, circ0106714 could suppress CRC by sponging miR‐942‐5p and releasing DLG2, thus promoting YAP phosphorylation.

中文翻译：

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Circ0106714通过使miR‐942‐5p海绵化并通过Hippo‐YAP信号释放DLG2来抑制结直肠癌的肿瘤发生

这项研究旨在研究circ0106714-miR-942-5p-discs大同源物2（DLG2）（一种新型的相互作用基因组）在结直肠癌（CRC）中的作用。使用生物信息学方法发现circ0106714是CRC中最显着下调的环状RNA，我们研究了circ0106714海绵miR‐942-5p和释放DLG2的能力是否会通过Hippo-YES-associated protein（YAP）影响CRC的发育信号。我们首先采用qRT-PCR和免疫印迹分别检测信使RNA（mRNA）和蛋白质表达。然后进行小鼠肿瘤异种移植的实时成像，以研究circ0106714对体内肿瘤进展的影响。随后进行了记者基因检测，以验证SW480和HCT116细胞系中circ0106714，miR-942-5p和DLG2 mRNA之间的预测靶向关系。除了使用流式细胞仪进行凋亡和细胞周期谱分析外，还进行了CCK-8和克隆灶形成试验来评估细胞存活率。随后进行伤口愈合测定和transwell侵袭测定，以评估细胞系的迁移和侵袭。研究发现，在人类CRC组织和细胞系中circ0106714和DLG2显着下调，而miR‐942-5p显着上调。但是，circ0106714上调通过靶向miR-942-5p来显着抑制体内肿瘤的进展，并抑制体外肿瘤细胞的恶性表型。在这项研究中还发现，miR-942-5p可以直接靶向DLG2 mRNA，从而增强CRC细胞的恶性表型。我们甚至发现DLG2过表达导致YAP磷酸化增强，DLG2的关键下游效应子。该下游效应物已被证明在CRC细胞系中具有肿瘤抑制能力。总之，circ0106714可以通过海绵化miR‐942-5p并释放DLG2从而抑制CRC，从而促进YAP磷酸化。