NEAT1 upregulates EGCG-induced CTR1 to enhance cisplatin sensitivity in lung cancer cells.
Platinum-based drugs are the firstline of treatment for non-small cell lung cancer (NSCLC), but resistance to these drugs is a major obstacle to effective chemotherapy. Our previous study revealed that the green tea polyphenol, EGCG, induced cisplatin transporter CTR1 (copper transporter 1) and enhanced cisplatin sensitivity in ovarian cancer. In this study, we found that EGCG upregulated CTR1 and increased platinum accumulation in NSCLC (A549, H460 and H1299) cells, cDDP-resistant A549 cells and a nude mouse xenograft model. Cisplatin-induced inhibition of cell growth was enhanced by EGCG treatment in vitro and in vivo. MicroRNA hsa-mir-98-5p appears to suppress CTR1 gene expression, while long non-coding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1) appears to enhance it. Bioinformatics analysis showed that hsa-mir-98-5p has specific complementary binding sites for NEAT1. In addition, hsa-mir-98-5p was predicted to be a putative CTR1 target. NEAT1 may act as a competing endogenous lncRNA to upregulate EGCG-induced CTR1 by sponging hsa-mir-98-5p in NSCLC. Our findings reveal a novel mechanism how NEAT1 upregulates EGCG-induced CTR1 and enhances cisplatin sensitivity in vitro and in vivo, and suggest EGCG could serve as an effective adjuvant chemotherapeutic in lung cancer treatment.
Department of Nutrition and Food Hygiene, Key Laboratory of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.
Pan
P
Jiang
Department of Nutrition and Food Hygiene, Key Laboratory of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.
Xiaoyue
X
Wu
Beijing Research Institute for Nutritional Resources, Beijing, China.
Xuemin
X
Wang
Department of Pathology, Affiliated Nanjing First Hospital of Nanjing Medical University, Nanjing, China.
Wenbin
W
Huang
Department of Nutrition and Food Hygiene, Key Laboratory of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.
Qing
Q
Feng
D000072283:A549 Cells; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D017024:Chemotherapy, Adjuvant / Q000379:methods; D002945:Cisplatin / Q000494:pharmacology* / Q000627:therapeutic use; D000079923:Copper Transporter 1; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008168:Lung / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D015854:Up-Regulation; D023041:Xenograft Model Antitumor Assays
D016588:Anticarcinogenic Agents; D027682:Cation Transport Proteins; D000079923:Copper Transporter 1; C546084:MIRN98 microRNA, human; D035683:MicroRNAs; C577276:NEAT1 long non-coding RNA, human; D062085:RNA, Long Noncoding; D034741:RNA, Small Interfering; C490079:SLC31A1 protein, human; D002392:Catechin; C045651:epigallocatechin gallate; D002945:Cisplatin
CTR1; NEAT1; cisplatin; hsa-mir-98-5p; lung cancer