NEAT1 upregulates EGCG-induced CTR1 to enhance cisplatin sensitivity in lung cancer cells

Abstract

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.

In silico identification of thiostrepton as an inhibitor of cancer stem cell growth and an enhancer for chemotherapy in non–small‐cell lung cancer

“…In this study, an increased level of miR‐98 (a tumour suppressor) was observed in response to thiostrepton treatment. Because miR‐98 is reportedly down‐regulated in many cancer types, its targets, such as Myc, Kras and Wnt signalling, are generally oncogenic . The exact targets for thiostrepton‐induced miR‐98 induction in NSCLC warrant further investigation.…”

Chemosensitizing effect of shRNA-mediated ERCC1 silencing on a Xuanwei lung adenocarcinoma cell line and its clinical significance

“…One explanation for this discrepancy is that many factors are involved in platinum resistance. In addition to ERCC1, many other genes, such as YAP (38) and NEAT1 (39), play important roles in the complicated biological events underlying the resistance process. ERCC1 expression level and function can be affected by post-transcriptional modifications.…”

Dietary Intervention by Phytochemicals and Their Role in Modulating Coding and Non-Coding Genes in Cancer

“…A novel mechanism of decreasing drug resistance in lung cancer by EGCG, was proved to be via NEAT1 upregulation, leading to an increased response to cisplatin and preventing activation of drug resistance mechanisms in lung cancer [192]. …”