The Department of Medical Oncology, Huizhou Municipal Center Hospital, No. 41 Eling North Road, Huizhou, 516001, Guangdong, China.
The Department of Gastrointestinal Surgery, Huizhou Municipal Center Hospital, Huizhou, China.
Biochem Genet. 2022 Dec;60(6):2250-2267. doi: 10.1007/s10528-022-10207-6. Epub 2022 Mar 21.
Colorectal cancer (CRC) is a common malignancy in both men and women, and the prognosis of CRC patients is still unsatisfactory. We aimed to identify novel effective diagnostic and prognostic targets for CRC. The study design is listed as below: we first confirmed the linear correlation between the expression of disheveled 3 (DVL3) and circular RNA_0101802 (circ_0101802) in CRC tissues, and their functional correlation in CRC cells was verified by rescue assays. Subsequently, bioinformatics databases were used to search the common interacted microRNAs (miRNAs) of DVL3 and circ_0101802, and compensation experiments were conducted to verify the functional correlation between miR-665 and DVL3 in CRC cells. Finally, xenograft tumor model was established to confirm the role of circ_0101802/miR-665/DVL3 axis in tumor growth in vivo. The expression of DVL3 and circ_0101802 was elevated in CRC tissues and cell lines, and high levels of DVL3 and circ_0101802 were closely associated with short survival time of CRC patients. Circ_0101802 silencing restrained the proliferation, migration, and tube formation abilities and induced the apoptosis of CRC cells. Circ_0101802 silencing-induced anti-tumor effects in CRC cells were partly reversed by DVL3 overexpression. miR-665 was an intermediary molecule between circ_0101802 and DVL3, and circ_0101802 could positively regulate DVL3 protein expression by sponging miR-665 in CRC cells. DVL3 overexpression partly overturned miR-665 overexpression-mediated anti-tumor effects in CRC cells. Circ_0101802 knockdown significantly suppressed xenograft tumor growth in vivo. In conclusion, circ_0101802 contributed to CRC progression by targeting miR-665/DVL3 signaling.
结直肠癌（CRC）是男性和女性中常见的恶性肿瘤，CRC 患者的预后仍然不尽人意。我们旨在确定 CRC 的新型有效诊断和预后靶点。研究设计如下：我们首先确认了结直肠癌组织中 DVL3 和环状 RNA_0101802（circ_0101802）表达之间的线性相关性，并通过挽救实验验证了它们在 CRC 细胞中的功能相关性。随后，利用生物信息学数据库搜索 DVL3 和 circ_0101802 的常见相互作用微小 RNA（miRNA），并进行补偿实验验证 miR-665 与 CRC 细胞中 DVL3 之间的功能相关性。最后，建立异种移植肿瘤模型，以确认 circ_0101802/miR-665/DVL3 轴在体内肿瘤生长中的作用。DVL3 和 circ_0101802 的表达在 CRC 组织和细胞系中升高，高水平的 DVL3 和 circ_0101802 与 CRC 患者的短生存时间密切相关。circ_0101802 沉默抑制 CRC 细胞的增殖、迁移和管形成能力，并诱导其凋亡。circ_0101802 沉默在 CRC 细胞中诱导的抗肿瘤作用部分被 DVL3 过表达逆转。miR-665 是 circ_0101802 和 DVL3 之间的中间分子，circ_0101802 通过在 CRC 细胞中海绵 miR-665 正向调节 DVL3 蛋白表达。DVL3 过表达部分推翻了 miR-665 过表达在 CRC 细胞中介导的抗肿瘤作用。circ_0101802 敲低显著抑制体内异种移植肿瘤的生长。总之，circ_0101802 通过靶向 miR-665/DVL3 信号通路促进 CRC 的进展。
