# The harmonies played by miR-302/367 cluster in pluripotency, reprogramming, and rejuvenation **Authors:** Melika Zamanian, Sharif Moradi, Hossein Baharvand PMC · DOI: 10.1093/stcltm/szaf072 · 2026-02-15 ## TL;DR This paper reviews how the miR-302/367 cluster helps control cell fate, reprogramming, and aging, with potential for treating age-related diseases. ## Contribution The paper highlights the miR-302/367 cluster's dual role in promoting pluripotency and countering aging, with potential for rejuvenation therapies. ## Key findings - The miR-302/367 cluster suppresses aging markers like p16INK4a and p21 during reprogramming. - It reduces oxidative stress and fibrosis, suggesting therapeutic use in age-related conditions. - Combining miR-302/367 with delivery systems like lipid nanoparticles could enable targeted rejuvenation. ## Abstract The conserved, pluripotency-associated miR-302/367 cluster coordinates cell fate and aging via epigenetic, cell cycle, and signaling regulation. Highly expressed in pluripotent stem cells and silenced during differentiation, it promotes efficient somatic cell reprogramming by suppressing senescence mediators (eg, p16INK4a, p21) and replacing oncogenes such as c-Myc to minimize tumorigenic risks. Beyond pluripotency, the miR-302/367 cluster reduces oxidative stress, mitochondrial dysfunction, and fibrosis, indicating therapeutic potential in age-associated conditions such as neurodegenerative, ocular, and fibrotic diseases. This review summarizes the dual ability of miR-302/367 cluster in promoting cell state transitions and transiently resetting cellular aging to enable healthspan extension. We critically discuss the pivotal role of miR-302/367 cluster in pluripotency and reprogramming while countering aging hallmarks. Finally, we explore how combining single-miRNA therapeutics with clinically viable delivery systems (lipid nanoparticles and extracellular vesicles) can link cellular reprogramming with targeted rejuvenation therapies. Graphical Abstract ## Linked entities - **Genes:** CDKN2A (cyclin dependent kinase inhibitor 2A) [NCBI Gene 1029], CDKN1A (cyclin dependent kinase inhibitor 1A) [NCBI Gene 1026], MYC (MYC proto-oncogene, bHLH transcription factor) [NCBI Gene 4609] ## Full-text entities - **Genes:** LARP7 (La ribonucleoprotein 7, transcriptional regulator) [NCBI Gene 51574] {aka ALAZS, HDCMA18P, PIP7S, hLARP7}, Mir302a (microRNA 302a) [NCBI Gene 723920] {aka Mirn302, Mirn302a, mir-302a, mmu-mir-302}, CCNG2 (cyclin G2) [NCBI Gene 901], AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, HDAC2 (histone deacetylase 2) [NCBI Gene 3066] {aka HD2, KDAC2, RPD3, YAF1}, MYC (MYC proto-oncogene, bHLH transcription factor) [NCBI Gene 4609] {aka MRTL, MYCC, bHLHe39, c-Myc}, MIR367 (microRNA 367) [NCBI Gene 442912] {aka MIRN367, hsa-mir-367}, SOX2 (SRY-box transcription factor 2) [NCBI Gene 6657] {aka ANOP3, MCOPS3}, BMI1 (BMI1 proto-oncogene, polycomb ring finger) [NCBI Gene 648] {aka FLVI2/BMI1, PCGF4, RNF51, flvi-2/bmi-1}, TGFBR2 (transforming growth factor beta receptor 2) [NCBI Gene 7048] {aka AAT3, FAA3, LDS1B, LDS2, LDS2B, MFS2}, MIR302D (microRNA 302d) [NCBI Gene 442896] {aka MIRN302D, mir-302d}, APP (amyloid beta precursor protein) [NCBI Gene 351] {aka AAA, ABETA, ABPP, AD1, APPI, CTFgamma}, NODAL (nodal growth differentiation factor) [NCBI Gene 4838] {aka HTX5}, ZEB1 (zinc finger E-box binding homeobox 1) [NCBI Gene 6935] {aka AREB6, BZP, DELTAEF1, FECD6, NIL2A, PPCD3}, NANOG (Nanog homeobox) [NCBI Gene 79923], TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, FGF2 (fibroblast growth factor 2) [NCBI Gene 2247] {aka BFGF, FGF-2, FGFB, HBGF-2}, UBE3A (ubiquitin protein ligase E3A) [NCBI Gene 7337] {aka ANCR, AS, E6-AP, EPVE6AP, HPVE6A, PIX1}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, CDK2 (cyclin dependent kinase 2) [NCBI Gene 1017] {aka CDKN2, p33(CDK2)}, LIF (LIF interleukin 6 family cytokine) [NCBI Gene 3976] {aka CDF, DIA, HILDA, MLPLI}, INHBE (inhibin subunit beta E) [NCBI Gene 83729], KDM1A (lysine demethylase 1A) [NCBI Gene 23028] {aka AIMAH3, AOF2, BHC110, CPRF, KDM1, LSD1}, LATS2 (large tumor suppressor kinase 2) [NCBI Gene 26524] {aka KPM}, CCND2 (cyclin D2) [NCBI Gene 894] {aka KIAK0002, MPPH3}, NFE2L2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 4780] {aka IMDDHH, NRF2, Nrf-2}, DICER1 (dicer 1, ribonuclease III) [NCBI Gene 23405] {aka DCR1, Dicer, Dicer1e, GLOW, HERNA, K12H4.8-LIKE}, VIM (vimentin) [NCBI Gene 7431], Hif1a (hypoxia inducible factor 1, alpha subunit) [NCBI Gene 15251] {aka HIF-1-alpha, HIF1-alpha, HIF1alpha, MOP1, bHLHe78}, IGF1 (insulin like growth factor 1) [NCBI Gene 3479] {aka IGF, IGF-I, IGFI, MGF}, NR2F2 (nuclear receptor subfamily 2 group F member 2) [NCBI Gene 7026] {aka ARP-1, ARP1, CHTD4, COUPTF2, COUPTFB, COUPTFII}, MIR302A (microRNA 302a) [NCBI Gene 407028] {aka MIRN302, MIRN302A, hsa-mir-302, mir-302a}, HMOX1 (heme oxygenase 1) [NCBI Gene 3162] {aka HMOX1D, HO-1, HSP32, bK286B10}, ACTA1 (actin alpha 1, skeletal muscle) [NCBI Gene 58] {aka ACTA, ASMA, CFTD, CFTD1, CFTDM, CMYO2A}, MECP2 (methyl-CpG binding protein 2) [NCBI Gene 4204] {aka AUTSX3, MRX16, MRX79, MRXS13, MRXSL, PPMX}, POU5F1 (POU class 5 homeobox 1) [NCBI Gene 5460] {aka OCT3, OCT4, OCT4Borf1, OTF-3, OTF3, OTF4}, BMP1 (bone morphogenetic protein 1) [NCBI Gene 649] {aka OI13, PCOLC, PCP, TLD}, DGCR8 (DGCR8 microprocessor complex subunit) [NCBI Gene 54487] {aka C22orf12, DGCRK6, Gy1, pasha}, MIR21 (microRNA 21) [NCBI Gene 406991] {aka MIRN21, hsa-mir-21, miR-21, miRNA21}, CCND1 (cyclin D1) [NCBI Gene 595] {aka BCL1, D11S287E, PRAD1, U21B31}, PTEN (phosphatase and tensin homolog) [NCBI Gene 5728] {aka 10q23del, BZS, CWS1, DEC, GLM2, MHAM}, ABCB1 (ATP binding cassette subfamily B member 1) [NCBI Gene 5243] {aka ABC20, CD243, CLCS, ENPAT, GP170, MDR1}, ASGR1 (asialoglycoprotein receptor 1) [NCBI Gene 432] {aka ASGPR, ASGPR1, CLEC4H1, HL-1}, CDKN2A (cyclin dependent kinase inhibitor 2A) [NCBI Gene 1029] {aka ARF, CAI2, CDK4I, CDKN2, CMM2, INK4}, MIR145 (microRNA 145) [NCBI Gene 406937] {aka MIRN145, miR-145, miRNA145}, MIR126 (microRNA 126) [NCBI Gene 406913] {aka MIRN126, miRNA126, mir-126}, RBL2 (RB transcriptional corepressor like 2) [NCBI Gene 5934] {aka BRUWAG, P130, Rb2}, 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}, MBD2 (methyl-CpG binding domain protein 2) [NCBI Gene 8932] {aka DMTase, NY-CO-41}, KDM1B (lysine demethylase 1B) [NCBI Gene 221656] {aka AOF1, C6orf193, LSD2}, CDKN1A (cyclin dependent kinase inhibitor 1A) [NCBI Gene 1026] {aka CAP20, CDKN1, CIP1, MDA-6, P21, SDI1}, TET1 (tet methylcytosine dioxygenase 1) [NCBI Gene 80312] {aka CXXC6, LCX, bA119F7.1}, ATAD2 (ATPase family AAA domain containing 2) [NCBI Gene 29028] {aka ANCCA, CT137, PRO2000}, CCL5 (C-C motif chemokine ligand 5) [NCBI Gene 6352] {aka D17S136E, RANTES, SCYA5, SIS-delta, SISd, TCP228}, CCN2 (cellular communication network factor 2) [NCBI Gene 1490] {aka CTGF, HCS24, IBP-8, IGFBP8, KMD, NOV2}, MIR17HG (miR-17-92a-1 cluster host gene) [NCBI Gene 407975] {aka C13orf25, LINC00048, MIHG1, MIRH1, MIRHG1, NCRNA00048}, MIR29A (microRNA 29a) [NCBI Gene 407021] {aka MIRN29, MIRN29A, hsa-mir-29, hsa-mir-29a, miRNA29A, mir-29a}, DROSHA (drosha ribonuclease III) [NCBI Gene 29102] {aka ETOHI2, HSA242976, RANSE3L, RN3, RNASE3L, RNASEN}, CDH1 (cadherin 1) [NCBI Gene 999] {aka Arc-1, BCDS1, CD324, CDHE, ECAD, LCAM} - **Diseases:** fibrosis (MESH:D005355), prostate cancer (MESH:D011471), degenerative diseases (MESH:D019636), inflammatory (MESH:D007249), PD (MESH:D010300), mitochondrial dysfunction (MESH:D028361), demyelination (MESH:D003711), tumorigenic (MESH:D002471), cervical carcinoma (MESH:D002583), age-related visual disorders (MESH:D014786), ischemic injury (MESH:D017202), diabetes (MESH:D003920), cancer (MESH:D009369), AD (MESH:D000544), Myocardial infarction (MESH:D009203), cardiovascular disorders (MESH:D002318), neurotoxicity (MESH:D020258), teratoma (MESH:D013724), weight loss (MESH:D015431), AMD (MESH:D008268), peritoneal fibrosis (MESH:D056627), cytotoxicity (MESH:D064420), liver fibrosis (MESH:D008103), breast cancer (MESH:D001943), pulmonary fibrosis (MESH:D011658), oncogenesis (MESH:D063646), impaired cardiac function (MESH:D006331), myocardial damage (MESH:D009202), germ cell tumors (MESH:D009373), Unilateral ureteral obstruction (MESH:D014517), heart tumor (MESH:D006338), DKD (MESH:D003928), ESCC (MESH:D000091622), metabolic dysfunction (MESH:D008659), age-related disorders (MESH:D008569), hypoxia (MESH:D000860), glioblastoma (MESH:D005909) - **Chemicals:** gold (MESH:D006046), 2'-MOE (-), Tranylcypromine (MESH:D014191), PS (MESH:D010758), PEG (MESH:D011092), polyethylenimines (MESH:D011094), RepSox (MESH:C550621), VPA (MESH:D014635), CCl4 (MESH:D002251), Sodium butyrate (MESH:D020148), ND (MESH:D009354), 3-morpholinosydnonimine hydrochloride (MESH:C002385), LNA (MESH:C477371), streptozotocin (MESH:D013311), MPTP (MESH:D015632), lipid (MESH:D008055), nucleotide (MESH:D009711), RG-101 (MESH:C000718752), bleomycin (MESH:D001761), NE (MESH:D009356), N-acetylgalactosamine (MESH:D000116), hyaluronic acid (MESH:D006820), d-galactose (MESH:D005690), CoCl2 (MESH:C018021) - **Species:** Mus musculus (house mouse, species) [taxon 10090], Caenorhabditis elegans (species) [taxon 6239], Homo sapiens (human, species) [taxon 9606], Streptococcus pneumoniae (species) [taxon 1313] - **Cell lines:** HDF — Homo sapiens (Human), Induced pluripotent stem cell (CVCL_RJ31), MEF — Mus musculus (Mouse), Finite cell line (CVCL_9115), HLF — Homo sapiens (Human), Adult hepatocellular carcinoma, Cancer cell line (CVCL_2947), HFF — Homo sapiens (Human), Finite cell line (CVCL_3285), RPE — Homo sapiens (Human), Spontaneously immortalized cell line (CVCL_0145), retinal pigment — Homo sapiens (Human), Spontaneously immortalized cell line (CVCL_IQ82), ESCs — Homo sapiens (Human), Embryonic stem cell (CVCL_UI95), LX-2 — Homo sapiens (Human), Transformed cell line (CVCL_5792), HMEC — Homo sapiens (Human), Transformed cell line (CVCL_0307), hASC — Homo sapiens (Human), Induced pluripotent stem cell (CVCL_A9ZM), HMRSV5 — Mus musculus (Mouse), Transformed cell line (CVCL_5U93), hCEC — Homo sapiens (Human), Telomerase immortalized cell line (CVCL_AQ45) ## Figures 4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12907026/full.md --- Source: https://tomesphere.com/paper/PMC12907026