Exosomal lncRNA HEIH promotes cisplatin resistance in tongue squamous cell carcinoma via targeting miR-3619-5p/HDGF axis
Xiaowei Wang, Huiming Yu, Zhifen Yu, Dazhao Wang
Abstract
BACKGROUND: Accumulating evidence has suggested that long noncoding RNAs (lncRNAs) are involved in the progression of types of human cancers. It has been known that exosomes can mediate cell-cell crosstalk by transferring lncRNAs in tumor progression. This study aimed to investigate the role of exosomal lncRNA HEIH on cisplatin (DDP) resistance in tongue squamous cell carcinoma (TSCC). METHODS: The expression of HEIH in human oral keratinocytes cell line (HOK), DDP-sensitive TSCC cell line (SCC4/S) and DDP-resistant TSCC cell line (SCC4/DDP) was measured. SCC4/S and SCC4/DDP cells were transfected with sh-HEIH to examine TSCC cell proliferation and apoptosis. The DDP-resistant exosomes were extracted and identified. The expression of miR‑3619-5p and TDGF in DDP-sensitive recipient cells was determined. The binding capacity between HEIH and miR‑3619-5p, along with miR‑3619-5p and TDGF was verified. RESULTS: HEIH expression was significantly upregulated in SCC4/DDP cells. Downregulation of HEIH inhibited DDP resistance and cell proliferation and promoted cell apoptosis. HEIH acted as a competing endogenous RNA (ceRNA) for miR‑3619-5p to upregulate HDGF expression. Exosomal HEIH promoted cell proliferation and drug resistance and inhibited cell apoptosis by sponging miR‑3169-5p and upregulating HDGF. CONCLUSION: Exosomal HEIH acted as a ceRNA for miR‑3619-5p to upregulate HDGF, thereby promoting DDP resistance in TSCC cells.