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IncRNA ZFAS1 contributes to the radioresistance of nasopharyngeal carcinoma cells by sponging hsa-miR-7-5p to upregulate ENO2.

ABSTRACT: Previous research revealed that lncRNA ZFAS1 could promote nasopharyngeal carcinoma (NPC) by inhibiting its downstream target axis. However, the association between ZFAS1 and radioresistant NPC cells is unclear. This study aimed to explore the roles of ZFAS1 in the radioresistance of NPC. Bioinformatics analysis was conducted to identify the significant factors (ENO2 and miR-7-5p) that contributed to the radioresistance of NPC cells. After performing qRT-PCR analysis, we found that the expression of ZFAS1 and ENO2 was upregulated in NPC cells but that the miR-7-5p expression was downregulated in the same samples. Apart from that, we noticed that ZFAS1 inhibition enhanced the sensitivity of NPC cells to radiation therapy by repressing cell proliferation and promoting cell apoptosis. Subsequently, we found that ZFAS1 could sponge miR-7-5p to upregulate ENO2, which was the target of miR-7-5p. Experimental results also indicated that the suppression of miR-7-5p inhibited the sensitivity of NPC cells to radiation therapy, thereby suppressing ENO2 expression. Overall, our findings suggested that ZFAS1 contributed to the radioresistance of NPC cells by regulating the miR-7-5p/ENO2 axis and that ZFAS1 might be a potential therapeutic target for addressing the radioresistance of NPC cells.

SUBMITTER: Peng J

PROVIDER: S-EPMC7849681 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Circular RNAs (circRNAs) are a new class of single-stranded RNAs that form a continuous loop with crucial role in regulation of gene expression. Because their circular conformation conforms numerous properties, circRNAs have been investigated recently to demonstrate their important role in the development and progression of various cancers. However, the function of circRNAs and their regulatory outcomes in cervical cancer (CC) have rarely been explored. In this study, the role and molecular mechanism of hsa_circ_0107593 in cervical cancer are demonstrated. Quantitative polymerase chain reaction (qRT-PCR) was used to determine the expression of hsa_circ_0107593 and three miRNAs (hsa-miR-20a-5p, 93-5p, and 106b-5p) in paired CC tissues (tumor tissue vs. adjacent normal cervical tissue), CC cell lines, and human normal cervical epithelial immortalized cell line. A series of functional experiments were conducted to assess the function of hsa_circ_0107593 in CC development. The Receiver Operating Characteristic (ROC) curve was plotted to estimate the diagnostic value of hsa_circ_0107593 in CC. The dual-luciferase reporter assay was used to explore the interaction between hsa_circ_0107593 and hsa-miR-20a-5p/93-5p/106b-5p. Bioinformatic analysis was conducted to predict the target mRNAs, pathways, and functional enrichment. The results revealed that hsa_circ_0107593 has low expression in CC tissues and CC cell lines. Moreover, negative correlations of hsa_circ_0107593 expression were found against tumor diameter, FIGO stage, and myometrial invasion. Also, hsa_circ_0107593 impedes CC cell proliferation, migration, and invasion. Based on ROC curve analysis, hsa_circ_0107593 could serve as a diagnostic biomarker. Its low expression may indicate increased patient's risk to developing cervical cancer. Mechanistically, hsa_circ_0107593 serves as a sponge of hsa-miR-20a-5p, hsa-miR-93-5p, and hsa-miR-106b-5p. Collectively, our study implies that hsa_circ_0107593 has tumor-suppressing activity in CC by physically binding with hsa-miR-20a-5p, hsa-miR-93-5p, and hsa-miR-106b-5p.

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IncRNA ZFAS1 contributes to the radioresistance of nasopharyngeal carcinoma cells by sponging hsa-miR-7-5p to upregulate ENO2.

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