4.8 Article

circSETD3 regulates MAPRE1 through miR-615-5p and miR-1538 sponges to promote migration and invasion in nasopharyngeal carcinoma

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ONCOGENE
卷 40, 期 2, 页码 307-321

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SPRINGERNATURE
DOI: 10.1038/s41388-020-01531-5

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资金

  1. National Natural Science Foundation of China [81672683, 81702907, 81772901, 81772928, 81803025, 81972776, 82072374]
  2. Natural Science Foundation of Hunan Province [2018JJ3704, 2018JJ3815, 2018SK21210, 2018SK21211, 2019JJ50872, 2019JJ50778, 2020JJ4125]
  3. Fundamental Research Funds for the Central South University [2019zzts712, 2019zzts727]

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This study revealed that circSETD3 promotes invasion and migration of NPC cells by competitively adsorbing miR-615-5p and miR-1538, thus regulating the expression of MAPRE1. This suggests circSETD3 could be a potential molecular marker and therapeutic target for NPC.
Circular RNAs (circRNAs) play an essential role in tumorigenesis and development. However, they have rarely been investigated in nasopharyngeal carcinoma (NPC). This study aimed to investigate the role of circRNA in the invasion and metastasis of NPC. We screened and verified the high expression of circSETD3 in NPC cell lines using RNA sequencing (RNA-Seq) and verified the results of NPC biopsy samples using real-time quantitative polymerase chain reaction (qRT-PCR) and in situ hybridization (ISH). In vivo and in vitro experiments indicated that circSETD3 could promote NPC cell invasion and migration. We compared the proteomic data of NPC cells before and after the overexpression or knockdown of circSETD3 in combination with bioinformatics prediction and experimental verification. It was found that circSETD3 competitively adsorbs to miR-615-5p and miR-1538 and negates their inhibitory effect on MAPRE1 mRNA, thereby upregulating the expression of MAPRE1. The upregulated MAPRE1 then inhibits the acetylation of alpha-tubulin, promotes the dynamic assembly of microtubules, and enhances the invasion and migration capabilities of NPC cells. The results of this study suggest that circSETD3 is a novel molecular marker and a potential target for NPC diagnosis and treatment.

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