Hsa_circ_0002473 inhibits GH3 cell proliferation and GH secretion as a competitive endogenous RNA for has-miR-4645-3p
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Abstract
Growth hormone deficiency (GHD) diagnosis still lacks a gold standard or ideal diagnostic marker. Unlike other epigenetic mechanisms, non-coding RNAs regulate post-transcriptional levels. The information on non-coding RNAs in the field of GHD is limited. Therefore, this study aimed to explore the role of hsa_circ_0002473 as a competitive endogenous RNA for has-miR-4645-3p in attenuating the inhibitory effect of has-miR-4645-3p on SSTR2. In this study, we screened three significantly expressed circular RNAs (circRNAs) in five children with GHD, and selected the highest expressed hsa_circ_0002473 as the study object, and screened has-miR-4645-3p, which is the most likely to bind to hsa_circ_0002473, according to the microRNA (miRNA)-circRNA regulatory network, to study the role and mechanism of has-miR-4645-3p as a competitive endogenous RNA of has-miR-4645-3p on GH3 cells. Somatostatin receptor 2 (SSTR2) inhibits GH3 cell proliferation, and miRNA binding to SSTR2 inhibits the latter expression. Both bioinformatics and dual-luciferase reporter analyses showed targeting relationships between hsa_circ_0002473 and has-miR-4645-3p and between has-miR-4645-3p and SSTR2. We constructed the hsa_circ_0002473/has-miR-4645-3p axis and transfected it into GH3 cells and found that overexpression of hsa_circ_0002473 inhibited the proliferation and growth hormone (GH) secretion of GH3 cells, and that hsa-miR-4645-3p promoted the proliferation and GH secretion of GH3 cells by targeting SSTR2. Co-culture revealed that the inhibitory effect of hsa_circ_0002473 was reversed by has-miR-4645-3p. In conclusion, our findings suggest that hsa_circ_0002473 can act as a competitive endogenous RNA for has-miR-4645-3p to regulate GH3 cell proliferation and secretion by targeting SSTR2.
Acknowledgments
The authors would like to thank Editage (www.editage.cn) for English language editing.
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Research ethics: This study was approved by the Ethics Committee of Xiaoshan District Hospital of Traditional Chinese Medicine and Orthopedics (Protocol Number: (2021)01). The study was conducted in accordance with the Declaration of Helsinki.
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Informed consent: Written informed consent was obtained from children with GHD and healthy volunteers who underwent physical examinations at the Xiaoshan District Hospital.
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Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
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Use of Large Language Models, AI and Machine Learning Tools: None declared.
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Conflict of interest: The authors state no conflict of interest.
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Research funding: This research is supported by the Zhejiang province medicine and health science and technology project (Number: 2023KY223), and the Hangzhou Medical and health science and technology project (Number: B20210051).
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Data availability: Not applicable.
References
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© 2024 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Review
- Effect and safety of aromatase inhibitors for the treatment of short stature in male children and adolescents: a meta-analysis of randomized controlled trials
- Original Articles
- Do hybrid closed loop insulin pump systems improve glycemic control and reduce hospitalizations in poorly controlled type 1 diabetes?
- Long-term effectiveness and safety of long-acting growth hormone preparation in children with growth hormone deficiency
- Gonadal changes in children and adolescents with congenital adrenal hyperplasia
- Hsa_circ_0002473 inhibits GH3 cell proliferation and GH secretion as a competitive endogenous RNA for has-miR-4645-3p
- Through the eyes of the parents: a transdiagnostic psychiatric perspective for children with differences of sexual development
- Experiences and psychological issues affecting parents of children born with atypical genitalia in India
- Case Reports
- A rare case of central precocious puberty in a male infant with adrenal hypoplasia congenita
- Gly183Ser homozygous mutation of the steroid 5-a reductase type 2 (SRD5A2) gene in a Brazilian patient: case report
- Novel PIK3R1 gene mutation associated with SHORT syndrome: a case report of a 15-year-old female
- Mineralocorticoid receptor antagonist monotherapy in pediatric non-classical 11β-hydroxylase deficiency
- A rare case of skeletal dysplasia: biallelic variant in ACAN gene
- Letter to the Editor
- Another look at the necessity of polysomnography for infants with Prader-Willi syndrome prior to initiation of growth hormone therapy
- Annual Reviewer Acknowledgment
- Reviewer Acknowledgment
Articles in the same Issue
- Frontmatter
- Review
- Effect and safety of aromatase inhibitors for the treatment of short stature in male children and adolescents: a meta-analysis of randomized controlled trials
- Original Articles
- Do hybrid closed loop insulin pump systems improve glycemic control and reduce hospitalizations in poorly controlled type 1 diabetes?
- Long-term effectiveness and safety of long-acting growth hormone preparation in children with growth hormone deficiency
- Gonadal changes in children and adolescents with congenital adrenal hyperplasia
- Hsa_circ_0002473 inhibits GH3 cell proliferation and GH secretion as a competitive endogenous RNA for has-miR-4645-3p
- Through the eyes of the parents: a transdiagnostic psychiatric perspective for children with differences of sexual development
- Experiences and psychological issues affecting parents of children born with atypical genitalia in India
- Case Reports
- A rare case of central precocious puberty in a male infant with adrenal hypoplasia congenita
- Gly183Ser homozygous mutation of the steroid 5-a reductase type 2 (SRD5A2) gene in a Brazilian patient: case report
- Novel PIK3R1 gene mutation associated with SHORT syndrome: a case report of a 15-year-old female
- Mineralocorticoid receptor antagonist monotherapy in pediatric non-classical 11β-hydroxylase deficiency
- A rare case of skeletal dysplasia: biallelic variant in ACAN gene
- Letter to the Editor
- Another look at the necessity of polysomnography for infants with Prader-Willi syndrome prior to initiation of growth hormone therapy
- Annual Reviewer Acknowledgment
- Reviewer Acknowledgment
