PMID- 35196205 OWN - NLM STAT- MEDLINE DCOM- 20220408 LR - 20220531 IS - 2165-5987 (Electronic) IS - 2165-5979 (Print) IS - 2165-5979 (Linking) VI - 13 IP - 3 DP - 2022 Mar TI - Circular RNA SET domain protein 3 promotes nasopharyngeal carcinoma proliferation, cisplatin resistance, and protein kinase B / mammalian target of rapamycin pathway activation by modulating microRNA-147a expression. PG - 5843-5854 LID - 10.1080/21655979.2022.2036907 [doi] AB - Circular RNA (circRNA) plays a crucial role in the establishment and progression of nasopharyngeal carcinoma (NPC). Understanding the role of circRNA in NPC is helpful to find new therapeutic targets for NPC. The purpose of this study was to explore the effects of circRNA SET domain protein 3 (circSETD3) on protein kinase B (Akt)/ mammalian target of rapamycin (mTOR) signaling pathway and cisplatin (DDP) resistance to NPC and explore its downstream mechanism. The results showed that circSETD3 was upregulated in NPC tissues and was related to DDP resistance to NPC. Functional experiments revealed that circSETD3 knockdown inhibited NPC proliferation and increased DDP sensitivity and apoptosis rate. The promotion effect of circSETD3 overexpression on NPC proliferation and DDP resistance and inhibition effect on apoptosis was reversed by elevated miR-147a. CircSETD3 knockdown or miR-147a overexpression prevented Akt/mTOR pathway's activation. In terms of the mechanism, circSETD3 acted as a sponge for miR-147a. Xenotransplantation experiments showed that knockdown circSETD3 or DDP treatment could restrain tumor growth, and the effect of DDP was enhanced by knockdown of circSETD3. In conclusion, the results of this study confirm that circSETD3 promotes NPC proliferation and DDP resistance by regulating miR-147a, and circSETD3/miR-147a axis may serve as a potential therapeutic target for NPC in the future. FAU - Deng, Gang AU - Deng G AD - Department of Otorhinolaryngology, Wuhan No. 1 Hospital of Hubei Province, Wuhan City, HuBei Province, China. FAU - Wang, Fei AU - Wang F AD - Department of Otorhinolaryngology, People's Hospital of Qinghai Province, Xining City, QingHai Province, China. FAU - Song, YiSa AU - Song Y AD - Department of Otorhinolaryngology, People's Hospital of Qinghai Province, Xining City, QingHai Province, China. LA - eng PT - Journal Article PL - United States TA - Bioengineered JT - Bioengineered JID - 101581063 RN - 0 (MIRN147 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (RNA, Circular) RN - EC 2.1.1.- (Histone Methyltransferases) RN - EC 2.1.1.43 (SETD3 protein, human) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - Q20Q21Q62J (Cisplatin) SB - IM MH - Cell Line, Tumor MH - Cell Proliferation/genetics MH - Cisplatin/pharmacology MH - Drug Resistance, Neoplasm/genetics MH - Histone Methyltransferases MH - Humans MH - *MicroRNAs/genetics MH - Nasopharyngeal Carcinoma/genetics/metabolism MH - *Nasopharyngeal Neoplasms/metabolism MH - Proto-Oncogene Proteins c-akt/metabolism MH - *RNA, Circular/genetics MH - TOR Serine-Threonine Kinases/genetics/metabolism PMC - PMC8973767 OTO - NOTNLM OT - CircSETD3 OT - cisplatin resistance OT - microRNA-147a OT - nasopharyngeal carcinoma COIS- No potential conflict of interest was reported by the author(s). EDAT- 2022/02/24 06:00 MHDA- 2022/04/09 06:00 PMCR- 2022/02/23 CRDT- 2022/02/23 17:11 PHST- 2022/02/23 17:11 [entrez] PHST- 2022/02/24 06:00 [pubmed] PHST- 2022/04/09 06:00 [medline] PHST- 2022/02/23 00:00 [pmc-release] AID - 2036907 [pii] AID - 10.1080/21655979.2022.2036907 [doi] PST - ppublish SO - Bioengineered. 2022 Mar;13(3):5843-5854. doi: 10.1080/21655979.2022.2036907.