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Targeting SNHG3/miR-186-5p reverses the increased m6A level caused by platinum treatment through regulating METTL3 in esophageal cancer

Authors
  • Zhang, Mingxin1
  • Bai, Minghua2
  • Wang, Li1
  • Lu, Ning1
  • Wang, Jia1
  • Yan, Rong1
  • Cui, Manli1
  • Yan, Honglin1
  • Zhang, Lingmin3
  • 1 The First Affiliated Hospital of Xi’an Medical University,
  • 2 Liaocheng People’s Hospital,
  • 3 The First Affiliated Hospital of Xi’an Jiaotong University,
Type
Published Article
Journal
Cancer Cell International
Publisher
Springer (Biomed Central Ltd.)
Publication Date
Feb 17, 2021
Volume
21
Identifiers
DOI: 10.1186/s12935-021-01747-9
PMID: 33596916
PMCID: PMC7887820
Source
PubMed Central
Keywords
Disciplines
  • Primary Research
License
Unknown

Abstract

Background Platinum-based chemotherapy is a mainstay for treating esophageal cancer patients. In this manuscript, we have provided clues for influence of platinum on overall m6A level and further investigated the potential regulatory mechanism. Methods qRT-PCR was used to measure SNHG3 and miR-186-5p expression; ELISA and western blot were used to measure the expression of METTL3. CCK8 was used to measure the cell proliferation rate. Caspase 3/7 activity was used to measure the apoptosis rate. Dual luciferase reporter gene assay and RNA pull down assay were used to investigate the potential crosstalk between miR-186-5p and SNHG3; and miR-186-5p and METTL3. Results m6A level was increased when treated with platinum (CDDP, CPB and L-OHP). Besides, SNHG3 expression was induced and miR-186-5p expression was suppressed by platinum. Furthermore, SNHG3 could promote the m6A level, however miR-186-5p inhibited the m6A level through targeting METTL3. SNHG3 interacts with miR-186-5p to negatively regulate the expression of miR-186-5p; and miR-186-5p might bind to the 3′UTR of METTL3 to regulate its expression. Conclusion Platinum can increase the overall m6A level of esophageal cancer. SNHG3/miR-186-5p, induced by platinum, was involved in regulating m6A level by targeting METTL3. Our manuscript has provided clues that regulating m6A level might be a novel way to enhance the platinum efficacy.

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