Department of Pathology, The Second Hospital, Hebei Medical University, Shijiazhuang, China.
Department of Oncology, The Fourth Hospital, Hebei Medical University, Shijiazhuang, China.
Thorac Cancer. 2020 Mar;11(3):738-747. doi: 10.1111/1759-7714.13326. Epub 2020 Feb 3.
Our recent studies have indicated that miR-153-3p is downregulated in the esophageal squamous cell carcinoma (ESCC) cell lines and tissues. Upregulation of miR-153-3p was found to inhibit migration and invasion of ESCC cells. However, whether miR-153-3p regulates the cisplatin sensitivity in ESCC cells remains unclear. In this study, we explored whether and how miR-153-3p regulates the proliferation and confers cisplatin resistance in ESCC by targeting the Nrf-2 protein.
Eca109 cell line was transfected with microRNA-153-3p mimics or Nrf-2siRNA and cell proliferation and cisplatin resistance were studied. A dual-luciferase reporter assay was performed on Eca109 cells cotransfected with the wild-type/mutant 3'UTR sequences of Nrf-2 and control or microRNA-153-3p mimics. We determined the correlation between microRNA-153-3p and Nrf-2 expression in human ESCC samples and explored the effect of Nrf-2 in the overall survival rate of ESCC patients.
MiR-153-3p significantly suppressed cell proliferation and increased the sensitivity of Eca-109 cells to cisplatin. MiR-153-3p showed a negative correlation with Nrf-2 in human esophageal carcinoma tissues. MiR-153-3p suppressed the expression of Nrf-2 via binding to its 3'-UTR region. Furthermore, inhibition of Nrf-2 also decreased cell proliferation and increased the sensitivity of Eca109 cells to cisplatin. High expression of Nrf-2 in human ESCC samples was associated with poor overall survival of ESCC patients.
MiR-153-3p inhibits cell proliferation and confers cisplatin resistance by downregulating Nrf-2 expression in Eca-109 cells. Thus, miR-153-3p/Nrf-2 may play an important role in conferring cisplatin resistance in ESCC. Nrf-2 appears to be a promising therapeutic target for ESCC.
我们最近的研究表明，miR-153-3p 在食管鳞状细胞癌（ESCC）细胞系和组织中下调。上调 miR-153-3p 被发现抑制 ESCC 细胞的迁移和侵袭。然而，miR-153-3p 是否调节 ESCC 细胞中的顺铂敏感性尚不清楚。在这项研究中，我们通过靶向 Nrf-2 蛋白探讨了 miR-153-3p 是否以及如何调节 ESCC 细胞的增殖并赋予顺铂耐药性。
用 microRNA-153-3p 模拟物转染 Eca109 细胞系，研究细胞增殖和顺铂耐药性。对 Eca109 细胞进行双荧光素酶报告基因检测，共转染野生型/突变型 3'UTR 序列的 Nrf-2 和对照或 microRNA-153-3p 模拟物。我们确定了人 ESCC 样本中 microRNA-153-3p 和 Nrf-2 表达之间的相关性，并探讨了 Nrf-2 对 ESCC 患者总生存率的影响。
miR-153-3p 显著抑制 Eca-109 细胞的增殖并增加其对顺铂的敏感性。miR-153-3p 在人食管癌组织中与 Nrf-2 呈负相关。miR-153-3p 通过结合其 3'-UTR 区域抑制 Nrf-2 的表达。此外，抑制 Nrf-2 也降低了 Eca109 细胞的增殖并增加了其对顺铂的敏感性。人 ESCC 样本中 Nrf-2 的高表达与 ESCC 患者的总体生存率差相关。
miR-153-3p 通过下调 Eca-109 细胞中的 Nrf-2 表达抑制细胞增殖并赋予顺铂耐药性。因此，miR-153-3p/Nrf-2 可能在 ESCC 中赋予顺铂耐药性中发挥重要作用。Nrf-2 似乎是 ESCC 的一个有前途的治疗靶点。
