Chemoradiotherapy Center of Oncology, The Affiliated People's Hospital of Ningbo University, Zhejiang, Ningbo, 315000, RPChina.
Bioengineered. 2021 Dec;12(2):9885-9892. doi: 10.1080/21655979.2021.1999373.
This study investigated the role of miRNA-144 (miR-144) targeting of the long noncoding DNAJC3-AS1 in regulating breast cancer chemosensitivity. Real-time quantitative polymerase chain reaction was employed to detect the levels of miR-144 in different drug-resistant cells. MTT assays were used to measure the proliferation of cells in different treatment groups. The apoptosis rate of transfected cells was detected by flow cytometry. Western blotting was used to detect levels of DNAJC3-AS1 protein and of autophagy-related proteins. A double luciferase report experiment was performed to evaluate the targeting effect of miR-144 on DNAJC3-AS1. The level of miR-144 was significantly downregulated in MCF-7 doxorubicin-resistant cells. Upregulated expression of miR-144 increased the doxorubicin sensitivity of drug-resistant cells and the rate of apoptosis. DNAJC3-AS1 was the direct target of miR-144; overexpression of DNAJC3-AS1 significantly rescued the apoptosis induced by miR-144 and reversed the inhibition of autophagy by miR-144. Overexpression of miR-144 can reduce drug resistance in breast cancer cells by inhibiting autophagy or targeting DNAJC3-AS1 for downregulation. miR-144/DNAJC3-AS1 provide a new target for reducing drug resistance in breast cancer.
本研究探讨了 miRNA-144（miR-144）靶向长非编码 DNAJC3-AS1 在调节乳腺癌化疗敏感性中的作用。实时定量聚合酶链反应用于检测不同耐药细胞中 miR-144 的水平。MTT 法检测不同处理组细胞的增殖情况。流式细胞术检测转染细胞的凋亡率。Western blot 检测 DNAJC3-AS1 蛋白和自噬相关蛋白的水平。双荧光素酶报告实验评估 miR-144 对 DNAJC3-AS1 的靶向作用。MCF-7 多柔比星耐药细胞中 miR-144 的水平明显下调。上调 miR-144 的表达增加了耐药细胞对多柔比星的敏感性和细胞凋亡率。DNAJC3-AS1 是 miR-144 的直接靶标；过表达 DNAJC3-AS1 显著挽救了 miR-144 诱导的凋亡，并逆转了 miR-144 对自噬的抑制作用。过表达 miR-144 可通过抑制自噬或靶向下调 DNAJC3-AS1 来降低乳腺癌细胞的耐药性。miR-144/DNAJC3-AS1 为降低乳腺癌耐药性提供了新的靶点。
