miR-487b-5p Regulates Temozolomide Resistance of Lung Cancer Cells Through LAMP2-Medicated Autophagy.
Temozolomide (TMZ) is a standard agent used in the treatment of various types of cancers, including lung carcinoma, but TMZ resistance is common and accounts for many treatment failures. We investigated miRNA-487b-5p (miR-487b-5p) was highly expressed in A549 and H1299 cells which acquired TMZ resistance. Suppression of miR-487b-5p had overt effects on cellular proliferation and migration in the presence of TMZ. On the other hand, knockdown of miR-487b-5p resulted in increased survival and moderate tumor growth in vivo. In addition, the decreased cellular proliferation following miR-487b-5p suppression was linked to enhanced autophagy, evident by drastically increased levels of LC3-II, BECLIN1, and LAMP2 when miR-487b-5p was knocked down. Further analysis revealed that LAMP2 might be the target gene of miR-487b-5p. In conclusion, our study suggested that miR-487b-5p may be a potential biomarker of acquired TMZ resistance in lung cancer cells, and miR-487b-5p inhibition can be further explored as a chemotherapy target in the treatment of TMZ-resistant lung carcinoma.
Department of Respirology, Nanjing Medical University Affiliated Wuxi Second Hospital , Wuxi, China .
Liang
L
Bao
Department of Respirology, Nanjing Medical University Affiliated Wuxi Second Hospital , Wuxi, China .
Lei
L
Lv
Department of Respirology, Nanjing Medical University Affiliated Wuxi Second Hospital , Wuxi, China .
Jinping
J
Feng
Department of Respirology, Nanjing Medical University Affiliated Wuxi Second Hospital , Wuxi, China .
Yuyu
Y
Chen
Department of Respirology, Nanjing Medical University Affiliated Wuxi Second Hospital , Wuxi, China .
Xinhua
X
Wang
Department of Respirology, Nanjing Medical University Affiliated Wuxi Second Hospital , Wuxi, China .
Shuguang
S
Han
Department of Respirology, Nanjing Medical University Affiliated Wuxi Second Hospital , Wuxi, China .
Hongqing
H
Zhao
D000072283:A549 Cells; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D000071186:Beclin-1 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D052119:Lysosomal-Associated Membrane Protein 2 / Q000235:genetics* / Q000378:metabolism; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D009841:Oligonucleotides / Q000235:genetics / Q000378:metabolism; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction; D000077204:Temozolomide; D014162:Transfection
D018906:Antineoplastic Agents, Alkylating; C491997:BECN1 protein, human; D000071186:Beclin-1; C497811:LAMP2 protein, human; D052119:Lysosomal-Associated Membrane Protein 2; C477012:MAP1LC3A protein, human; C568526:MIRN487 microRNA, human; D035683:MicroRNAs; D008869:Microtubule-Associated Proteins; D009841:Oligonucleotides; D003606:Dacarbazine; D000077204:Temozolomide