Department of Gastrointestinal Surgery, The First People's Hospital of Changzhou, Changzhou, Jiangsu 213029, P.R. China.
Department of Urology Surgery, The First People's Hospital of Changzhou, Changzhou, Jiangsu 213029, P.R. China.
Int J Mol Med. 2020 Dec;46(6):1973-1982. doi: 10.3892/ijmm.2020.4747. Epub 2020 Oct 7.
Circular RNAs (circRNAs) have been reported to be involved in the progression of colorectal cancer (CRC). However, the biological role of circCCDC66 in CRC remains unclear. Therefore, the present study aimed to elucidate the mechanisms through which circCCDC66 affects the hypoxia‑induced progression of CRC. It was found that hypoxia promoted the progression of CRC and upregulated the expression of circCCDC66. Furthermore, circCCDC66‑knockdown reduced viability, migration and invasion, and enhanced the apoptosis of hypoxia‑exposed CRC cells. Using the starBase database, it was identified that circCCDC66 may bind to miR‑3140. Subsequently, it was confirmed that circCCDC66 serves as a sponge of miR‑3140 and the depletion of miR‑3140 partly abolished the effects of circCCDC66 on the phenotype of hypoxia‑exposed CRC cells. In addition, miR‑3140 was validated to inhibit the autophagy pathway. The use of an autophagy inducer partially reversed the miR‑3140 overexpression‑induced inhibition of the viability and invasion, and the promotion of the apoptosis of hypoxia‑exposed CRC cells. In summary, the findings of the present study demonstrated that circCCDC66 facilitates the development of CRC cells under hypoxic conditions via regulation of miR‑3140/autophagy. These findings may provide a novel therapeutic option for patients with CRC.
环状 RNA(circRNAs)已被报道参与结直肠癌(CRC)的进展。然而,circCCDC66 在 CRC 中的生物学作用尚不清楚。因此,本研究旨在阐明 circCCDC66 影响 CRC 缺氧诱导进展的机制。研究发现,缺氧促进 CRC 的进展并上调 circCCDC66 的表达。此外,circCCDC66 敲低降低了缺氧暴露的 CRC 细胞的活力、迁移和侵袭,并增强了细胞凋亡。通过 starBase 数据库,鉴定出 circCCDC66 可能与 miR-3140 结合。随后,证实 circCCDC66 作为 miR-3140 的海绵,并且 miR-3140 的耗竭部分消除了 circCCDC66 对缺氧暴露的 CRC 细胞表型的影响。此外,miR-3140 被验证可抑制自噬途径。自噬诱导剂的使用部分逆转了 miR-3140 过表达诱导的对缺氧暴露的 CRC 细胞活力和侵袭的抑制作用,并促进了细胞凋亡。总之,本研究的结果表明,circCCDC66 通过调节 miR-3140/自噬促进缺氧条件下 CRC 细胞的发展。这些发现可能为 CRC 患者提供新的治疗选择。