# Differential microRNA Expression Profiles in Girls with Idiopathic Central Precocious Puberty and Premature Thelarche

**Authors:** Hye Jin Lee, Seon Joo Bae, Eu Seon Noh, Hye Young Jin, Il Tae Hwang, Seongho Ryu, Hwal Rim Jeong

PMC · DOI: 10.3390/ijms27041742 · International Journal of Molecular Sciences · 2026-02-11

## TL;DR

The study identifies distinct microRNA profiles in girls with early puberty variants, suggesting potential biomarkers for diagnosis and understanding pubertal development.

## Contribution

The study reveals unique exosomal miRNA expression patterns in idiopathic central precocious puberty and related conditions.

## Key findings

- Distinct exosomal miRNA expression patterns were observed among CPP, ET, and control groups.
- miR-30b-5p was upregulated in CPP, ET, and PT groups compared to controls.
- Pathway analysis linked miRNA changes to AGE–RAGE, MAPK, and mTOR signaling pathways.

## Abstract

Idiopathic central precocious puberty (CPP) is increasingly observed in girls. Premature thelarche (PT) and exaggerated thelarche (ET) are early pubertal variants that can be challenging to distinguish from CPP in clinical practice. Exosomal microRNAs are stable biomarkers capable of crossing the blood–brain barrier. Although miR-30b-5p has been reported to increase in pubertal boys and girls, human studies investigating microRNAs in CPP and puberty remain limited. To investigate exosomal microRNA expression profiles and associated pathways in early pubertal development, we conducted a cross-sectional study of 28 girls aged 6–8 years. Serum exosomal microRNA expression was analyzed using next-generation sequencing. Differentially expressed microRNAs (DEmiRNAs) between groups were identified, followed by pathway enrichment analysis. Distinct exosomal miRNA expression patterns were observed among the CPP, ET, and control groups, with 307 DEmiRNAs identified. The CPP, PT, and ET groups exhibited distinct miRNA expression profiles compared with the control group. miR-30b-5p was upregulated in the CPP, ET, and PT groups compared with the control group. Pathway enrichment analysis revealed the involvement of various signaling pathways including AGE–RAGE, MAPK, and mTOR signaling pathways. Serum exosomal microRNAs may serve as biomarkers for early puberty and provide insight into metabolic influences on pubertal development.

## Linked entities

- **Diseases:** idiopathic central precocious puberty (MONDO:0015713)

## Full-text entities

- **Genes:** Mir200b (microRNA 200b) [NCBI Gene 387243] {aka Mirn200b, mir-200b}, HIF1A (hypoxia inducible factor 1 subunit alpha) [NCBI Gene 3091] {aka HIF-1-alpha, HIF-1A, HIF-1alpha, HIF1, HIF1-ALPHA, MOP1}, KISS1R (KISS1 receptor) [NCBI Gene 84634] {aka AXOR12, CPPB1, GPR54, HH8, HOT7T175, KISS-1R}, MIR30C1 (microRNA 30c-1) [NCBI Gene 407031] {aka MIRN30C1, mir-30c-1}, Gnrh1 (gonadotropin releasing hormone 1) [NCBI Gene 14714] {aka Gnrh, Gnrh2, LHRH, Lhrh1, Lnrh, hpg}, MIR9-3 (microRNA 9-3) [NCBI Gene 407051] {aka MIRN9-3, hsa-mir-9-3, miRNA9-3, mir-9-3}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, RENBP (renin binding protein) [NCBI Gene 5973] {aka RBP, RNBP}, MIRLET7B (microRNA let-7b) [NCBI Gene 406884] {aka LET7B, MIRNLET7B, hsa-let-7b, let-7b}, GNRH1 (gonadotropin releasing hormone 1) [NCBI Gene 2796] {aka GNRH, GRH, LHRH, LNRH}, MKRN3 (makorin ring finger protein 3) [NCBI Gene 7681] {aka CPPB2, D15S9, RNF63, ZFP127, ZNF127}, Dlk1 (delta like non-canonical Notch ligand 1) [NCBI Gene 114587] {aka DLK-1, Pref-1, Zog}, LIN28B (lin-28 RNA binding posttranscriptional regulator B) [NCBI Gene 389421] {aka CSDD2}, Grin1 (glutamate ionotropic receptor NMDA type subunit 1) [NCBI Gene 24408] {aka GluN1, NMDAR1, NR1}, Mir15a (microRNA mir-15a) [NCBI Gene 104795671] {aka rno-mir-15a}, MIR223 (microRNA 223) [NCBI Gene 407008] {aka MIRN223, miRNA223, mir-223}, MIR378C (microRNA 378c) [NCBI Gene 100422867] {aka mir-378c}, Mir29b-1 (microRNA 29b-1) [NCBI Gene 387223] {aka Mirn29b, Mirn29b-1, mir-29b-1}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, MOK (MOK protein kinase) [NCBI Gene 5891] {aka RAGE, RAGE-1, RAGE1, STK30}, MIR145 (microRNA 145) [NCBI Gene 406937] {aka MIRN145, miR-145, miRNA145}, Mir375 (microRNA 375) [NCBI Gene 723900] {aka Mirn375, mir-375, mmu-mir-375}, MIR132 (microRNA 132) [NCBI Gene 406921] {aka MIRN132, miRNA132, mir-132}, MIR375 (microRNA 375) [NCBI Gene 494324] {aka MIRN375, hsa-mir-375, miRNA375, mir-375}, Mir664-2 (microRNA 664-2) [NCBI Gene 100314092] {aka rno-mir-664-2}, Mir429 (microRNA 429) [NCBI Gene 723865] {aka Mirn429, mir-429, mmu-mir-429}, PRKAB1 (protein kinase AMP-activated non-catalytic subunit beta 1) [NCBI Gene 5564] {aka AMPK, HAMPKb}, BDNF (brain derived neurotrophic factor) [NCBI Gene 627] {aka ANON2, BULN2}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, AGER (advanced glycosylation end-product specific receptor) [NCBI Gene 177] {aka RAGE, SCARJ1, sRAGE}, MIR29B1 (microRNA 29b-1) [NCBI Gene 407024] {aka MIRN29B1, miR-29b, miRNA29B1, mir-29b-1}, Zeb1 (zinc finger E-box binding homeobox 1) [NCBI Gene 21417] {aka 3110032K11Rik, AREB6, BZP, MEB1, Nil2, TCF-8}, Kiss1 (KiSS-1 metastasis-suppressor) [NCBI Gene 280287] {aka kisspeptin, metastatin}, MYC (MYC proto-oncogene, bHLH transcription factor) [NCBI Gene 4609] {aka MRTL, MYCC, bHLHe39, c-Myc}, KISS1 (KiSS-1 metastasis suppressor) [NCBI Gene 3814] {aka HH13, KiSS-1}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, MIR30C2 (microRNA 30c-2) [NCBI Gene 407032] {aka MIRN30C2, mir-30c-2}, Mir29a (microRNA 29a) [NCBI Gene 387222] {aka Mirn29a, mir-29a, mmu-mir-29a}, MIR30B (microRNA 30b) [NCBI Gene 407030] {aka MIRN30B, mir-30b}, DLK1 (delta like non-canonical Notch ligand 1) [NCBI Gene 8788] {aka DLK, DLK-1, Delta1, FA1, PREF1, Pref-1}
- **Diseases:** CPP (MESH:D011629), type 2 diabetes (MESH:D003924), breast cancer (MESH:D001943), CNT (MESH:C536209), PT (MESH:C536271), preterm birth (MESH:D047928), endocrine disorders (MESH:D004700), BA (MESH:D010024), hypertension (MESH:D006973), polycystic ovarian syndrome (MESH:D011085), metabolic disorders (MESH:D008659), ET (MESH:D000067251), hypoxic (MESH:D002534), Obese (MESH:D009765), overweight (MESH:D050177), cancer (MESH:D009369), precocious (MESH:C565500), injury to (MESH:D014947)
- **Chemicals:** LH (MESH:D007986), lipid (MESH:D008055), BA (-), E2 (MESH:D004958), sugar (MESH:D000073893)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090]

## Full text

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## Figures

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## References

53 references — full list in the complete paper: https://tomesphere.com/paper/PMC12941009/full.md

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Source: https://tomesphere.com/paper/PMC12941009