Department of Hematology and Oncology, China-Japan Union Hospital of Jilin University, Changchun City, China.
Bioengineered. 2021 Dec;12(1):3219-3228. doi: 10.1080/21655979.2021.1939577.
MicroRNAs exert crucial effects in the drug resistance. The purpose of this research was to investigate the miR-25-3p effects on DDP resistance in NSCLC. We used RT-qPCR to evaluate the expression of miR-25-3p. Cell growth was determined using MTS assay. Cellular bio-activity was analyzed via Colony formation, Annexin V/PI, and Transwell assay. Luciferase reporter assay was used to determine miR-25-3p and PTEN binding. Western blot was used to determine PTEN, PI3K, -AKT/AKT expression. In-vivo study was used to determine the effects of miR-25-3p on the tumor growth. Expression of miR-25-3p is increased in NSCLC cisplatin resistant A549 and H1299 cells. Furthermore, miR-25-3p mimic enhanced drug resistance, and accelerated cell invasion and metastasis. Moreover, miR-25-3p mimic resulted in the activation of PTEN/PI3K/AKT pathway. However, miR-25-3p inhibitors exhibited the opposite trend. We further identified PTEN as a potential target of miR-25-3p. PTEN knockout promoted cisplatin resistance, while PTEN mimic displayed opposite effects. Interestingly, miR-25-3p further boosted cisplatin resistance cells in vivo, and miR-25-3p inhibitors reduced the in-vivo tumor volume. MiR-25-3p/PTEN/PI3K/AKT axis might accelerate DDP tolerance in NSCLC, which may serve as a potential target for chemotherapy resistance in NSCLC.
微小 RNA （miRNA）在药物耐药中发挥着至关重要的作用。本研究旨在探讨 miR-25-3p 对非小细胞肺癌（NSCLC）顺铂耐药的影响。我们使用 RT-qPCR 评估 miR-25-3p 的表达。通过 MTS 测定评估细胞生长。通过集落形成、Annexin V/PI 和 Transwell 测定分析细胞生物活性。使用荧光素酶报告基因测定确定 miR-25-3p 和 PTEN 的结合。使用 Western blot 测定确定 PTEN、PI3K、-AKT/AKT 的表达。进行体内研究以确定 miR-25-3p 对肿瘤生长的影响。miR-25-3p 在 NSCLC 顺铂耐药的 A549 和 H1299 细胞中表达增加。此外，miR-25-3p 模拟物增强了耐药性，并加速了细胞侵袭和转移。此外，miR-25-3p 模拟物导致了 PTEN/PI3K/AKT 通路的激活。然而，miR-25-3p 抑制剂则表现出相反的趋势。我们进一步确定了 PTEN 是 miR-25-3p 的一个潜在靶标。PTEN 敲除促进了顺铂耐药，而 PTEN 模拟物则显示出相反的效果。有趣的是，miR-25-3p 进一步增强了体内顺铂耐药细胞的耐药性，而 miR-25-3p 抑制剂则降低了体内肿瘤体积。miR-25-3p/PTEN/PI3K/AKT 轴可能加速 NSCLC 对顺铂的耐受性，这可能成为 NSCLC 化疗耐药的潜在靶点。
