circRNA hsa_circ_0072107 aggravates myocardial hypertrophy via its function as a competitive endogenous RNA of miR‑516b‑5p

Mol Med Rep. 2025 Sep;32(3):232. doi: 10.3892/mmr.2025.13597. Epub 2025 Jun 20.

Abstract

The present study aimed to identify differentially expressed circRNAs in hypertrophic cardiac tissues and explored the potential regulatory role and mechanism of one differentially expressed circRNA in myocardial hypertrophy. RNA sequencing was used to identify differentially expressed circRNAs in hypertrophic and control cardiac tissues. CircRNA expression levels were verified by reverse transcription‑quantitative PCR. Isoproterenol (ISO) was used to induce hypertrophy of AC16 cells. The extent of cell hypertrophy was indicated by the cell size, protein/DNA ratio and levels of B‑type natriuretic peptide (BNP) and β‑myosin heavy chain (β‑MHC). The interactions between hsa_circ_0072107 and miR‑516b‑5p, as well as between miR‑516b‑5p and zinc ring finger protein 36 (ZFP36), were confirmed through dual luciferase assays, biotinylated probe pull‑down and anti‑AGO2 RNA immunoprecipitation assays. hsa_circ_0072107 was one of the most upregulated circRNAs in hypertrophic cardiac tissues. hsa_circ_0072107 overexpression and ISO treatment increased cell size, elevated the protein/DNA ratio and increased the levels of BNP and β‑MHC in AC16 cells, indicating that hsa_circ_0072107 aggravates AC16 hypertrophy. These changes induced by ISO treatment could be blocked by the knockdown of hsa_circ_0072107. The dual‑luciferase activity assay indicated that miR‑516b‑5p can bind to hsa_circ_0072107. miR‑516b‑5p binding site mutation blocked the effect of hsa_circ_0072107. ZFP36 is a target gene of miR‑516b‑5p, which suppresses AC16 hypertrophy. hsa_circ_0072107 overexpression alleviated the effect of miR‑516b‑5p overexpression on cell hypertrophy and ZFP36 expression. hsa_circ_0072107 is up‑regulated in hypertrophic cardiac tissues and potentially promotes AC16 hypertrophy and may play its role by acting as a competitive endogenous RNA of miR‑516b‑5p. Thus, hsa_circ_0072107 may be a novel target for the treatment of myocardial hypertrophy.

Keywords: RNA‑sequencing; circular RNA; competitive endogenous RNA; has_circ_0072107; myocardial hypertrophy.

MeSH terms

  • Animals
  • Cardiomegaly* / genetics
  • Cardiomegaly* / metabolism
  • Cardiomegaly* / pathology
  • Cell Line
  • Female
  • Gene Expression Regulation
  • Humans
  • Isoproterenol / pharmacology
  • Male
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Middle Aged
  • Myocytes, Cardiac / metabolism
  • Natriuretic Peptide, Brain / genetics
  • Natriuretic Peptide, Brain / metabolism
  • RNA, Circular* / genetics
  • RNA, Circular* / metabolism
  • RNA, Competitive Endogenous

Substances

  • RNA, Circular
  • MicroRNAs
  • Isoproterenol
  • Natriuretic Peptide, Brain
  • RNA, Competitive Endogenous