Department of Gastroenterology, Rizhao People's Hospital, Rizhao, 276800, Shandong, China.
Department of Endoscopy, Xiamen Hospital of Traditional Chinese Medicine, China.
Biomed Pharmacother. 2020 Apr;124:109740. doi: 10.1016/j.biopha.2019.109740. Epub 2020 Jan 20.
On account of the acquired drug resistance, the potency of cisplatin-based chemotherapy is far from satisfactory in rectal cancer. Increasing evidence has highlighted the crucial function of aberrantly expressed lncRNAs on the cisplatin resistance in multiple cancers. This research was the first attempt to decipher the underlying function and mechanism of long intergenic non-protein coding RNA 461 (LINC00461) in rectal cancer and also its relation to cisplatin resistance of rectal cancer. Data from this study revealed that LINC00461 expression was upregulated in rectal cancer cells. LINC00461 depletion restrained rectal cancer progression and sensitized rectal cancer cells to cisplatin. Molecular mechanism assays testified that LINC00461 bound with miR-593-5p. Besides, miR-593-5p upregulation improved the sensitivity of rectal cancer cells to cisplatin. Additionally, cyclin D1 (CCND1) was manifested to be a downstream target of miR-593-5p. Furthermore, CCND1 upregulation could reverse the effect of LINC00461 downregulation on rectal cancer progression and cisplatin resistance of rectal cancer. To sum up, LINC00461 mediates cisplatin resistance of rectal cancer by targeting miR-593-5p/CCND1 axis, shedding new light on the treatment of rectal cancer.
由于获得性耐药性,顺铂为基础的化疗在直肠癌中的疗效远不理想。越来越多的证据强调了长链非编码 RNA 461(LINC00461)在多种癌症中的顺铂耐药性方面的关键作用。这项研究首次试图揭示长链非编码 RNA 461(LINC00461)在直肠癌中的潜在功能和机制,以及它与直肠癌顺铂耐药性的关系。本研究的数据显示,LINC00461 在直肠癌细胞中表达上调。LINC00461 的缺失抑制了直肠癌的进展,并使直肠癌细胞对顺铂敏感。分子机制试验表明,LINC00461 与 miR-593-5p 结合。此外,miR-593-5p 的上调提高了直肠癌细胞对顺铂的敏感性。此外,细胞周期蛋白 D1(CCND1)被证明是 miR-593-5p 的下游靶标。此外,CCND1 的上调可以逆转 LINC00461 下调对直肠癌进展和直肠癌顺铂耐药性的影响。总之,LINC00461 通过靶向 miR-593-5p/CCND1 轴介导直肠癌的顺铂耐药性,为直肠癌的治疗提供了新的思路。