EIF4A3-induced circFIP1L1 represses miR-1253 and promotes radiosensitivity of nasopharyngeal carcinoma

Background Radiation is currently used to be a mainstay of salvage therapy for nasopharyngeal carcinoma (NPC), however, development of radioresistance largely limits the radiation efficacy. Circular RNAs (circRNAs) have been shown to affect NPC progression, but its role in radioresistance remain unc...

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Veröffentlicht in:Cellular and molecular life sciences : CMLS 2022-07, Vol.79 (7), p.357, Article 357
Hauptverfasser: Zhou, Xiangqi, Yuan, Guangjin, Wu, Yangjie, Yan, Sijia, Jiang, Qingshan, Tang, Sanyuan
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Sprache:eng
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Zusammenfassung:Background Radiation is currently used to be a mainstay of salvage therapy for nasopharyngeal carcinoma (NPC), however, development of radioresistance largely limits the radiation efficacy. Circular RNAs (circRNAs) have been shown to affect NPC progression, but its role in radioresistance remain unclear. Methods The circular structure of circFIP1L1(circ_0069740) was verified by RNA-sequencing, RT-PCR based on gDNA or cDNA, RNase R treatment, and actinomycin D treatment. Cellular localization of circFIP1L1 and miR-1253 was detected by nucleoplasmic separation and/or fluorescence in situ hybridization. Expression of non-coding RNAs and mRNAs was detected by qRT-PCR, protein expression was detected by Western blot. Functionally, EdU, CCK-8, and colony formation experiments were employed to assess cell proliferation, flow cytometry was adopted to estimate cell cycle and apoptosis. Xenograft tumor growth was performed to detect the role of circFIP1L1 in vivo. Mechanistically, we examined the interplay between miR-1253 and circFIP1L1 or EIF4A3 through dual-luciferase reporter assay. The potential regulatory impacts of EIF4A3 on circFIP1L1 or PTEN was examined by RNA immunoprecipitation and RNA pull-down assays. Results CircFIP1L1 overexpression and miR-1253 knockdown repressed NPC cell proliferation, facilitated NPC cell apoptosis, and enhanced NPC radiosensitivity. Mechanistically, circFIP1L1 was revealed to repress miR-1253 by binding to it, and EIF4A3 is a target gene of miR-1253. CircFIP1L1 regulated NPC proliferation, apoptosis, and radiosensitivity through miR-1253/EIF4A3. Moreover, we found that EIF4A3 bound to FIP1L1 mRNA transcript and induced circFIP1L1 formation, and thus stabilizing PTEN mRNA. Conclusion Our findings suggested that EIF4A3-induced circFIP1L1 repressed NPC cell proliferation, facilitated NPC cell apoptosis, and enhanced NPC radiosensitivity by miR-1253.
ISSN:1420-682X
1420-9071
DOI:10.1007/s00018-022-04350-x