Abstract
BackgroundThere is growing evidence of the role of long non-coding RNAs (lncRNAs) in cervical cancer (CC). The objective was to discuss whether exosomal lncRNA HNF1A-AS1 impacted drug resistance in CC via binding to microRNA-34b (miR-34b) and regulating TUFT1 expression.MethodsThe expression of HNF1A-AS1 in normal cervical epithelial cells, cisplatin (DDP)-sensitive cell line (HeLa/S) and DDP-resistant cell line (HeLa/DDP) cells were detected. HeLa/S and HeLa/DDP cells were interfered with HNF1A-AS1 to determine IC50, proliferation, colony formation and apoptosis of CC cells. The exosomes were isolated and identified. Subcellular localization of HNF1A-AS1, expression of miR-34b and TUFT1 in receptor cells were also verified. The binding site between HNF1A-AS1 and miR-34b, together with miR-34b and TUFT1 were confirmed. Tumorigenic ability of cells in nude mice was also detected.ResultsHNF1A-AS1 was upregulated in DDP-resistant cell line HeLa/DDP. Silencing HNF1A-AS1 suppressed CC cell proliferation and promoted its apoptosis. HNF1A-AS1 was found to act as a competing endogenous RNA (ceRNA) of miR-34b to promote the expression of TUFT1. Exosomes shuttled HNF1A-AS1 promoted the proliferation and drug resistance of CC cells and inhibited their apoptosis by upregulating the expression of TUFT1 and downregulating miR-34b. Furthermore, suppressed exosomal HNF1A-AS1 in combination with DDP inhibited tumor growth in nude mice.ConclusionOur study provides evidence that CC-secreted exosomes carrying HNF1A-AS1 as a ceRNA of miR-34b to promote the expression of TUFT1, thereby promoting the DDP resistance in CC cells.
Highlights
There is growing evidence of the role of long non-coding RNAs in cervical cancer (CC)
LncRNAs has been confirmed as competition for microRNA sponges in competing endogenous RNA networks, which is participate in modulates the expression of miRNA [14]. miRNA is an endogenous small non-coding RNA molecule (19–22 bases in length), which binds to the incomplete sequence homology site of mRNA’s 3′-untranslated region (3′-UTR), and leads to the degradation or inhibition of protein translation [15]
HNF1A‐AS1 is elevated in DDP‐resistant CC cells In order to explore the expression of HNF1A-AS1 in DDP-resistant CC cells, we used Reverse transcription quantitative polymerase chain reaction (RT-qPCR) to detect the expression of HNF1A-AS1 in human normal cervical epithelial cell line HcerEpic, DDP-sensitive CC cell line (HeLa/S) and DDP-resistant cell line (HeLa/DDP)
Summary
There is growing evidence of the role of long non-coding RNAs (lncRNAs) in cervical cancer (CC). The objective was to discuss whether exosomal lncRNA HNF1A-AS1 impacted drug resistance in CC via binding to microRNA-34b (miR-34b) and regulating TUFT1 expression. It is reported in a study that in breast cancer tissues, the expression of TUFT1 increased significantly [18]. A study has demonstrated that TUFT1 is a factor in the poor prognosis of various cancers [19]. Based on the aforementioned evidence, our study was performed to discuss whether CC-derived exosomes carrying HNF1AAS1 could act as a competing endogenous RNA (ceRNA) of miR-34b to increase the expression of TUFT1, thereby affecting DDP resistance, proliferation and apoptosis in CC cells. A series of experiments were performed in this study to justify the hypothesis
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