Lin Chen, Li Hongjun, Gao Huabin, Zheng Shuai, Wang Yu, Wang Yuting, Chen Yongyu, Zhu Zhenwei, Xia Pei, Shi Hujuan, Han Anjia
The Department of Pathology at the First Affiliated Hospital of Sun Yat-Sen University in Guangzhou, China.
The Oncology Department at Shenzhen Hospital of Southern Medical University in Shenzhen, China.
Heliyon. 2024 Oct 20;10(20):e39549. doi: 10.1016/j.heliyon.2024.e39549. eCollection 2024 Oct 30.
To investigate the functional role and the underlying molecular mechanisms associated with hsa_circ_0004194 in the context of colorectal cancer (CRC) and to elucidate its impact on cancer progression.
A notable and statistically significant decrease in the expression levels of hsa_circ_0004194 was observed specifically within CRC tissues when compared to non-tumor colorectal mucosa tissues. Functional evaluations, such as CCK8 assays, plate clone formation analysis, and transwell migration assays, our study revealed hsa_circ_0004194 significantly reduced the activity behavior of CRC cells. This overexpression of hsa_circ_0004194 effectively hindered these key cellular processes, demonstrating its role in suppressing the aggressive behaviors of CRC cells. Additionally, in vivo experiments utilizing mouse xenograft models exhibited that the upregulation of hsa_circ_0004194 significantly attenuated tumor growth, reduced tumor volume, and diminished liver metastasis. Further mechanistic investigation, through the utilization of RNA pull-down and luciferase reporter assays, uncovered that hsa_circ_0004194 sequestered hsa-miR-27a-3p, thereby enhancing retinoic acid X receptor α (RXRα)' expression which is in CRC cells. Moreover, this circular RNA also impeded the signaling pathway of Wnt/β-catenin.
Our study is the first to demonstrate that hsa_circ_0004194 exhibits downregulated expression in CRC and functions as a ceRNA by binding to and sequestering hsa-miR-27a-3p, thereby modulating the RXRα/β-catenin signaling pathway to inhibit CRC progression. This discovery suggests that hsa_circ_0004194 holds significant potential as a therapeutic biomarker for patients with CRC.
研究hsa_circ_0004194在结直肠癌（CRC）中的功能作用及潜在分子机制，并阐明其对癌症进展的影响。
与非肿瘤结直肠黏膜组织相比，在CRC组织中特异性观察到hsa_circ_0004194表达水平显著且有统计学意义的降低。通过CCK8检测、平板克隆形成分析和Transwell迁移检测等功能评估，我们的研究表明hsa_circ_0004194显著降低了CRC细胞的活性行为。hsa_circ_0004194的这种过表达有效阻碍了这些关键细胞过程，证明了其在抑制CRC细胞侵袭性行为中的作用。此外，利用小鼠异种移植模型的体内实验表明，hsa_circ_0004194的上调显著减弱了肿瘤生长，减小了肿瘤体积，并减少了肝转移。通过RNA下拉和荧光素酶报告基因检测的进一步机制研究发现，hsa_circ_0004194隔离了hsa-miR-27a-3p，从而增强了CRC细胞中视黄酸X受体α（RXRα）的表达。此外，这种环状RNA还阻碍了Wnt/β-连环蛋白信号通路。
我们的研究首次证明hsa_circ_0004194在CRC中表达下调，并通过结合和隔离hsa-miR-27a-3p作为ceRNA发挥作用，从而调节RXRα/β-连环蛋白信号通路以抑制CRC进展。这一发现表明hsa_circ_0004194作为CRC患者的治疗生物标志物具有巨大潜力。
