4.7 Article

MiR-92b-3p Inhibits Proliferation of HER2-Positive Breast Cancer Cell by Targeting circCDYL

期刊

出版社

FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2021.707049

关键词

MiR-92b-3p; circCDYL; cell proliferation; HER2-positive breast cancer; RNA induced silencing complex

资金

  1. National Key R&D Program of China [2017YFC1309103, 2017YFC1309104]
  2. Natural Science Foundation of China [81672594, 81772836, 81872139, 82072907, 8203000408]
  3. Clinical Innovation Project of Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory) [2018GZR0201004]
  4. Sun Yat-sen memorial hospital cultivation project for clinical research [SYS-C-201805]
  5. National Natural Science Foundation of China [51861125203]
  6. Beijing Xisike Clinical Oncology Research Foundation [Y-Roche2019/2-0078]
  7. Technology Development Program of Guangdong Province [2021A0505030082]
  8. Project of The Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation [2020B1212060018OF007]

向作者/读者索取更多资源

In this study, the high expression of circCDYL in HER2(+) breast cancer tissue was found to promote cell proliferation independent of the miR-1275-ULK1/ATG7 autophagic axis. MiR-92b-3p was shown to cleave circCDYL in a silencing-dependent manner, and both circCDYL and miR-92b-3p were identified as potential biomarkers for predicting clinical outcomes in HER2(+) breast cancer patients.
Objectives: Circular RNA (circRNA) is a novel class of RNA, which exhibits powerful biological function in regulating cellular fate of various tumors. Previously, we had demonstrated that over-expression of circRNA circCDYL promoted progression of HER2-negative (HER2(-)) breast cancer via miR-1275-ULK1/ATG7-autophagic axis. However, the role of circCDYL in HER2-positive (HER2(+)) breast cancer, in particular its role in modulating cell proliferation, one of the most important characteristics of cellular fate, is unclear. Materials and methods: qRT-PCR and in situ hybridization analyses were performed to examine the expression of circCDYL and miR-92b-3p in breast cancer tissues or cell lines. The biological function of circCDYL and miR-92b-3p were assessed by plate colony formation and cell viability assays and orthotopic animal models. In mechanistic study, circRNAs pull-down, RNA immunoprecipitation, dual luciferase report, western blot, immunohistochemical and immunofluorescence staining assays were performed. Results: CircCDYL was high-expressed in HER2(+) breast cancer tissue, similar with that in HER2(-) breast cancer tissue. Silencing HER2 gene had no effect on expression of circCDYL in HER2(+) breast cancer cells. Over-expression of circCDYL promoted proliferation of HER2(+) breast cancer cells but not through miR-1275-ULK1/ATG7-autophagic axis. CircRNA pull down and miRNA deep-sequencing demonstrated the binding of miR-92b-3p and circCDYL. Interestingly, circCDYL did not act as miR-92b-3p sponge, but was degraded in miR-92b-3p-dependent silencing manner. Clinically, expression of circCDYL and miR-92b-3p was associated with clinical outcome of HER2(+) breast cancer patients. Conclusion: MiR-92b-3p-dependent cleavage of circCDYL was an essential mechanism in regulating cell proliferation of HER2(+) breast cancer cells. CircCDYL was proved to be a potential therapeutic target for HER2(+) breast cancer, and both circCDYL and miR-92b-3p might be potential biomarkers in predicting clinical outcome of HER2(+) breast cancer patients.

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