# The Role and Mechanisms of miRNAs on Ovarian Granulosa Cells: A Literature Review

**Authors:** Siyu Chen, Jiawei Lu, Yuqian Si, Lei Chen, Ye Zhao, Lili Niu, Yan Wang, Xiaofeng Zhou, Linyuan Shen, Ya Tan, Li Zhu, Mailin Gan

PMC · DOI: 10.3390/genes17020121 · Genes · 2026-01-24

## TL;DR

This review explores how microRNAs regulate ovarian granulosa cells and their role in conditions like PCOS and POF.

## Contribution

The paper systematically integrates findings on miRNA mechanisms in granulosa cells across multiple models and diseases.

## Key findings

- miRNAs regulate granulosa cell functions through key pathways like PI3K/AKT/mTOR and TGF-β/SMAD.
- Exosomal miRNAs facilitate communication in the follicular environment.
- Nearly 200 miRNAs are linked to PCOS, highlighting their potential as therapeutic targets.

## Abstract

Background: Ovarian granulosa cells (GCs) play a pivotal role in folliculogenesis, and their dysfunction is central to disorders such as polycystic ovary syndrome (PCOS) and premature ovarian failure (POF). MicroRNAs (miRNAs) have emerged as crucial post-transcriptional regulators of GC homeostasis. Method: This review synthesizes current evidence by systematically analyzing relevant studies, integrating data from in vitro GC models, animal experiments, human cell lines, and clinical samples to elucidate the specific mechanisms by which miRNAs regulate GCs. Results: miRNAs precisely modulate GC proliferation, apoptosis, steroidogenesis, and oxidative stress responses by targeting key signaling pathways (e.g., PI3K/AKT/mTOR, TGF-β/SMAD) and functional genes (e.g., TP53, CYP19A1). Exosomal miRNAs serve as vital mediators of communication within the follicular microenvironment. To date, nearly 200 miRNAs have been associated with PCOS. Conclusions: miRNAs constitute a decisive regulatory network governing GC fate, offering promising therapeutic targets for PCOS and POF. However, significant challenges remain, primarily miRNA pleiotropy and the lack of follicle-specific delivery systems. Future clinical translation requires rigorous validation in human-relevant models.

## Linked entities

- **Genes:** TP53 (tumor protein p53) [NCBI Gene 7157], CYP19A1 (cytochrome P450 family 19 subfamily A member 1) [NCBI Gene 1588]
- **Diseases:** polycystic ovary syndrome (MONDO:0008487), premature ovarian failure (MONDO:0001119)

## Full-text entities

- **Genes:** AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, GLG1 (golgi glycoprotein 1) [NCBI Gene 2734] {aka CFR-1, ESL-1, MG-160, MG160}, PTGS2 (prostaglandin-endoperoxide synthase 2) [NCBI Gene 5743] {aka COX-2, COX2, GRIPGHS, PGG/HS, PGHS-2, PHS-2}, MIR3188 (microRNA 3188) [NCBI Gene 100422833] {aka mir-3188}, LATS1 (large tumor suppressor kinase 1) [NCBI Gene 9113] {aka WARTS, wts}, STAT3 (signal transducer and activator of transcription 3) [NCBI Gene 6774] {aka ADMIO, ADMIO1, APRF, HIES}, WT1 (WT1 transcription factor) [NCBI Gene 7490] {aka AWT1, GUD, NPHS4, WAGR, WIT-2, WT-1}, INHBA [NCBI Gene 443524], SLC25A24 (solute carrier family 25 member 24) [NCBI Gene 29957] {aka APC1, SCAMC-1, SCAMC1}, MIR130A (microRNA 130a) [NCBI Gene 406919] {aka MIRN130A, miRNA130A, mir-130a}, JAK3 (Janus kinase 3) [NCBI Gene 3718] {aka JAK-3, JAK3_HUMAN, JAKL, L-JAK, LJAK}, ATF2 (activating transcription factor 2) [NCBI Gene 1386] {aka CRE-BP1, CREB-2, CREB2, HB16, TREB7}, MIR107 (microRNA 107) [NCBI Gene 406901] {aka MIRN107, miR-107}, Bax (BCL2-associated X protein) [NCBI Gene 12028], MIR320A (microRNA 320a) [NCBI Gene 407037] {aka MIRN320, MIRN320A, hsa-mir-320a, mir-320a}, CDK9 (cyclin dependent kinase 9) [NCBI Gene 1025] {aka C-2k, CDC2L4, CTK1, PITALRE, TAK}, MIR33A (microRNA 33a) [NCBI Gene 407039] {aka MIR33, MIRN33, MIRN33A, hsa-mir-33, hsa-mir-33a, miR-33}, SIRT7 (sirtuin 7) [NCBI Gene 51547] {aka SIR2L7}, PAI-1 [NCBI Gene 100381267], CIRBP (cold inducible RNA binding protein) [NCBI Gene 1153] {aka CIRP}, BMP15 (bone morphogenetic protein 15) [NCBI Gene 9210] {aka GDF9B, ODG2, POF4}, Sp1 (trans-acting transcription factor 1) [NCBI Gene 20683] {aka 1110003E12Rik, Sp1-1}, APPL1 (adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1) [NCBI Gene 26060] {aka APPL, DIP13alpha, MODY14}, E2F1 (E2F transcription factor 1) [NCBI Gene 396142], MIR451A (microRNA 451a) [NCBI Gene 574411] {aka MIR451, MIRN451, hsa-mir-451, hsa-mir-451a, mir-451a}, MiR-21 [NCBI Gene 102466405], TAFAZZIN (tafazzin, phospholipid-lysophospholipid transacylase) [NCBI Gene 6901] {aka BTHS, CMD3A, EFE, EFE2, G4.5, LVNCX}, IGF1 (insulin like growth factor 1) [NCBI Gene 3479] {aka IGF, IGF-I, IGFI, MGF}, MIR520H (microRNA 520h) [NCBI Gene 574493] {aka MIRN520H}, MIR99A (microRNA 99a) [NCBI Gene 407055] {aka MIRN99A, mir-99a}, KPNA2 (karyopherin subunit alpha 2) [NCBI Gene 3838] {aka IPOA1, PTAC58, QIP2, RCH1, SRP1-alpha, SRP1alpha}, SMAD5 (SMAD family member 5) [NCBI Gene 4090] {aka DWFC, JV5-1, MADH5}, CDC42 (cell division cycle 42) [NCBI Gene 998] {aka CDC42Hs, G25K, TKS}, Nfat5 (nuclear factor of activated T cells 5) [NCBI Gene 54446] {aka B130038B15Rik, CAG-8, CAG80, NFATL1, OREBP, TonEBP}, CASP3 (caspase 3) [NCBI Gene 836] {aka CPP32, CPP32B, SCA-1}, Smad2 (SMAD family member 2) [NCBI Gene 17126] {aka 7120426M23Rik, Madh2, Madr2, Smad-2, mMad2}, ZHX2 (zinc fingers and homeoboxes 2) [NCBI Gene 22882] {aka AFR1, RAF}, MIR19B1 (microRNA 19b-1) [NCBI Gene 406980] {aka C13orf25, MIR19B, MIRH1, MIRHG1, MIRN19B1, miR-19b-1}, MIR383 (microRNA 383) [NCBI Gene 494332] {aka MIRN383, hsa-mir-383, mir-383}, TLR4 [NCBI Gene 554263], TXNIP (thioredoxin interacting protein) [NCBI Gene 10628] {aka ARRDC6, EST01027, HHCPA78, THIF, VDUP1}, PTX3 [NCBI Gene 100034672], BCL2A1 (BCL2 related protein A1) [NCBI Gene 597] {aka ACC-1, ACC-2, ACC1, ACC2, BCL2L5, BFL1}, Mir224 (microRNA 224) [NCBI Gene 723894] {aka Mirn224, mir-224, mmu-mir-224}, HNF4A (hepatocyte nuclear factor 4 alpha) [NCBI Gene 3172] {aka FRTS4, HNF4, HNF4a7, HNF4a8, HNF4a9, HNF4alpha}, MIR3940 (microRNA 3940) [NCBI Gene 100500888] {aka mir-3940}, NR5A1 (nuclear receptor subfamily 5 group A member 1) [NCBI Gene 395960] {aka Ad4BP, SF-1}, YAP1 (Yes1 associated transcriptional regulator) [NCBI Gene 10413] {aka COB1, YAP, YAP-1, YAP2, YAP65, YKI}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, IRS1 (insulin receptor substrate 1) [NCBI Gene 3667] {aka HIRS-1}, MIR145 (microRNA 145) [NCBI Gene 406937] {aka MIRN145, miR-145, miRNA145}, SRF (serum response factor) [NCBI Gene 6722] {aka MCM1}, Smad4 (SMAD family member 4) [NCBI Gene 17128] {aka D18Wsu70e, DPC4, Madh4}, PTEN (phosphatase and tensin homolog) [NCBI Gene 5728] {aka 10q23del, BZS, CWS1, DEC, GLM2, MHAM}, SMAD4 (SMAD family member 4) [NCBI Gene 4089] {aka DPC4, JIP, MADH4, MYHRS}, TYK2 (tyrosine kinase 2) [NCBI Gene 7297] {aka IMD35, JTK1}, STC1 [NCBI Gene 101112949], MIR15A (microRNA 15a) [NCBI Gene 406948] {aka MIRN15A, hsa-mir-15a, miRNA15A, mir-15a}, IL10RA (interleukin 10 receptor subunit alpha) [NCBI Gene 3587] {aka CD210, CD210a, CDW210A, HIL-10R, IL-10R1, IL10R}, RSPO2 (R-spondin 2) [NCBI Gene 340419] {aka CRISTIN2, HHRRD, TETAMS2}
- **Diseases:** inflammatory (MESH:D007249), POF (MESH:D016649), injury to (MESH:D014947), mitochondrial dysfunction (MESH:D028361), GCs (MESH:D006106), cancer (MESH:D009369), follicular atresia (MESH:D005497), endometrial cancer (MESH:D016889), PCOS (MESH:D011085), GC dysfunction (MESH:D006331), ovarian disorders (MESH:D010049), hepatocellular carcinoma (MESH:D006528)
- **Chemicals:** PIP2 (MESH:D019269), estradiol (MESH:D004958), bisphenol A (MESH:C006780), PIP3 (-), Steroid Hormone (MESH:D013256), ATP (MESH:D000255), lipid (MESH:D008055), ROS (MESH:D017382), glucose (MESH:D005947)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Ovis aries (domestic sheep, species) [taxon 9940], Sus scrofa (pig, species) [taxon 9823], Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606], Bos taurus (bovine, species) [taxon 9913], Gallus gallus (bantam, species) [taxon 9031]
- **Cell lines:** KGN — Homo sapiens (Human), Ovarian granulosa cell tumor, Cancer cell line (CVCL_0375)

## Full text

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## Figures

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## References

92 references — full list in the complete paper: https://tomesphere.com/paper/PMC12940779/full.md

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Source: https://tomesphere.com/paper/PMC12940779