Hsa_circ_0128846 was found to be the most significantly up‐regulated circRNA in our bioinformatics analysis. However, the role of hsa_circ_0128846 in colorectal cancer has not been explored. We thus aim to explore the influence and mechanism of hsa_circ_0128846 in colorectal cancer by sponging its downstream miRNA target miR‐1184. We collected 40 colorectal cancer patients’ tumour tissues to analyse the expression of hsa_circ_0128846, miR‐1184 and AJUBA using qRT‐PCR and Western blot where needed. Then, we constructed stably transfected SW480 and HCT116 cells to study the influence of hsa_circ_0128846, miR‐1184 and AJUBA on colorectal cancer cell phenotypes. To obtain reliable results, a plethora of experiments including RNA immunoprecipitation assay, flow cytometry, EdU incorporation assay, wound healing migration assay, transwell invasion assay and live imaging of nude mice xenograft assay were performed. The binding relationship between hsa_circ_0128846, miR‐1184 and AJUBA mRNA in colorectal cancer was validated by reported gene assay. In colorectal cancer tissues, circ_0128846 and AJUBA were both significantly up‐regulated, while miR‐1184 was significantly down‐regulated compared with healthy tissues. Meanwhile, hsa_circ_0128846 can absorb miR‐1184 to promote the progression of CRC in vivo and SW480 and HCT116 cell phenotypes in vitro. The knockdown of AJUBA, a downstream target of miR‐1184, reversed the effect of miR‐1184 in CRC cells via enhancing the phosphorylation of the Hippo/YAP signalling pathway proteins MST1, LATS1 and YAP. This study revealed that hsa_circ_0128846 contributed to the development of CRC by decreasing the expression of miR‐1184, thereby increasing AJUBA expression and inactivating Hippo/YAP signalling.

中文翻译：

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Hsa_circ_0128846 通过海绵化 hsa-miR-1184 和释放 AJUBA 和灭活 Hippo/YAP 信号传导促进结直肠癌的肿瘤发生。

在我们的生物信息学分析中，发现 Hsa_circ_0128846 是最显着上调的 circRNA。然而，尚未探索 hsa_circ_0128846 在结直肠癌中的作用。因此，我们旨在通过海绵下游 miRNA 靶标 miR-1184 来探索 hsa_circ_0128846 在结直肠癌中的影响和机制。我们收集了 40 名结直肠癌患者的肿瘤组织，以在需要时使用 qRT-PCR 和蛋白质印迹分析 hsa_circ_0128846、miR-1184 和 AJUBA 的表达。然后，我们构建了稳定转染的SW480和HCT116细胞，研究了hsa_circ_0128846、miR-1184和AJUBA对结直肠癌细胞表型的影响。为了获得可靠的结果，进行了大量实验，包括 RNA 免疫沉淀测定、流式细胞术、EdU 掺入测定、伤口愈合迁移测定、进行了 transwell 侵袭试验和裸鼠异种移植试验的活体成像。hsa_circ_0128846、miR-1184和AJUBA mRNA在结直肠癌中的结合关系通过报道的基因检测得到验证。在结直肠癌组织中，circ_0128846 和 AJUBA 均显着上调，而 miR-1184 与健康组织相比显着下调。同时，hsa_circ_0128846 可以吸收 miR-1184 以促进体内 CRC 和体外 SW480 和 HCT116 细胞表型的进展。AJUBA 是 miR-1184 的下游靶标，通过增强 Hippo/YAP 信号通路蛋白 MST1、LATS1 和 YAP 的磷酸化，逆转了 miR-1184 在 CRC 细胞中的作用。该研究表明，hsa_circ_0128846 通过降低 miR-1184 的表达促进 CRC 的发展，