MicroRNA-486-5p improves nonsmall-cell lung cancer chemotherapy sensitivity and inhibits epithelial–mesenchymal transition by targeting twinfilin actin binding protein 1

Journal of International Medical Research - Tập 47 Số 8 - Trang 3745-3756 - 2019
Xiaoyan Jin1, Wenyang Pang1, Qiang Zhang1, Haitao Huang1
1Department of Surgical Oncology, Zhejiang Taizhou Municipal Hospital, Taizhou, Zhejiang Province, China

Tóm tắt

ObjectiveTo investigate the role of microRNA-486-5p (miR-486-5p) in nonsmall-cell lung cancer (NSCLC) resistance to cisplatin.MethodsThis retrospective study examined tumours and normal lung tissues from patients with NSCLC. The levels of miR-486-5p in NSCLC and normal tissues were determined using reverse transcription–polymerase chain reaction. The binding site of miR-486-5p on twinfilin actin binding protein 1 (TWF1) mRNA was predicted using TargetScan and investigated using a luciferase reporter gene assay. Cytotoxicity assays were used to measure the sensitivity of A549 cells to cisplatin. Western blotting was used to measure the levels of specific proteins. The role of miR-486-5p in the resistance of A549 to cisplatin was verified in vivo using a nude mouse tumorigenicity assay.ResultsMiR-486-5p levels were downregulated in NSCLC tissues compared with normal lung tissues. Lower levels of miR-486-5p were associated with reduced overall survival of patients with NSCLC. The cisplatin-resistant NSCLC cell line, A549/DDP, had lower miR-486-5p levels compared with A549 cells. Luciferase reporter gene assays confirmed that miR-486-5p bound to the 3ʹ untranslated region of TWF1 mRNA. In vivo experiments demonstrated the inhibitory effect of miR-486-5p on chemotherapy resistance.ConclusionMiR-486-5p appears to play an important role in improving chemotherapy sensitivity to cisplatin.

Từ khóa


Tài liệu tham khảo

10.3322/caac.21338

10.3322/caac.21349

10.3389/fonc.2014.00292

10.1016/j.ejphar.2014.07.025

10.1016/j.ctrv.2016.01.003

10.1021/acsami.6b16500

Lan D, 2018, Am J Transl Res, 10, 1295

10.1016/0092-8674(93)90529-Y

10.2174/1871520618666180808125459

10.1016/j.brainres.2009.06.053

10.1007/s12032-009-9225-9

10.3390/ijms17030424

10.1016/j.canlet.2017.09.038

10.1038/ncomms2393

10.1093/annonc/mdu123

10.3390/ijms19051486

10.18632/oncotarget.22975

10.1038/s41598-017-00405-3

10.1016/j.bbrc.2014.02.073

10.1038/ng.451

10.1002/cm.20530

10.1038/sj.emboj.7601019

10.1073/pnas.0608725104

Duan Z, 1999, Clin Cancer Res, 5, 3445

10.1189/jlb.0410226

Palmgren S, 2002, J Cell Sci, 115, 881, 10.1242/jcs.115.5.881

Thông tin
Thông tin xuất bản

Journal of International Medical Research

Tập 47 Số 8

3745-3756

Thông tin tác giả