# Liposome-Mediated MicroRNA Delivery: An Additional Layer of Gene Network Regulation and Nuclear Reprogramming

**Authors:** Navid Ghasemzadeh, Fatemeh Pourrajab, Ali Dehghani Firoozabadi, Maryam Rahnama

PMC · DOI: 10.61186/ibj.4271 · Iranian Biomedical Journal · 2024-10-30

## TL;DR

This study explores using liposomes to deliver microRNAs for cell reprogramming, showing how they can regulate genes linked to pluripotency.

## Contribution

The study introduces liposome-mediated miRNA delivery as a non-transduction method for cell reprogramming.

## Key findings

- miR-302a and miR-34a regulate pluripotency factors OCT4, SOX2, and NANOG.
- Lipoplexes with miR-302a increased OCT4 expression, while miR-34a decreased it.
- LP-miRs can induce pluripotency precursors and influence cell lineage conversion.

## Abstract

Developing miRNA-mediated cell engineering introduces a novel technology for cell reprogramming and generating patient-specific tissues for therapeutic use, facilitating basic research on human adult stem cells. Furthermore, optimizing a reprogramming method without transduction minimizes the risk of tumorigenesis, especially for reprogrammed cells. This study aimed to explore the use of liposomes as vehicles for delivering miRNAs to cells, focusing on their role in regulating gene networks and facilitating nuclear reprogramming.

This study utilized cationic liposomal nanoparticles preserved under different conditions to introduce miRNAs into hMSCs. Using qPCR, the effective induction of pluripotency factors (OCT4, SOX2, and NANOG) was examined.

Results indicated that miR-302a and miR-34a regulate pluripotency by interacting with key transcription factors, including OCT4, SOX2, and NANOG. Notably, the expression pattern of OCT4 showed that lipoplexes containing miR-302a increased the expression of this gene, while in the case of miR-34a, it decreased. Additionally, the study found that pluripotency precursors can be induced by delivering LP-miRs.

LP-miRs, as small-molecule therapeutics, can influence reprogramming/engineering and the conversion of cells into other lineages. These findings have significant implications for our understanding of the mechanisms underlying the regulation of pluripotency and may have potential applications in regenerative medicine.

## Linked entities

- **Genes:** POU5F1 (POU class 5 homeobox 1) [NCBI Gene 5460], SOX2 (SRY-box transcription factor 2) [NCBI Gene 6657], NANOG (Nanog homeobox) [NCBI Gene 79923], MIR302A (microRNA 302a) [NCBI Gene 407028], MIR34A (microRNA 34a) [NCBI Gene 407040]

## Full-text entities

- **Genes:** MIR34A (microRNA 34a) [NCBI Gene 407040] {aka MIRN34A, miRNA34A, mir-34, mir-34a}, PARP1 (poly(ADP-ribose) polymerase 1) [NCBI Gene 142] {aka ADPRT, ADPRT 1, ADPRT1, ARTD1, PARP, PARP-1}, NOTCH1 (notch receptor 1) [NCBI Gene 4851] {aka AOS5, AOVD1, TAN1, hN1}, KLF4 (KLF transcription factor 4) [NCBI Gene 9314] {aka EZF, GKLF}, NR2F2 (nuclear receptor subfamily 2 group F member 2) [NCBI Gene 7026] {aka ARP-1, ARP1, CHTD4, COUPTF2, COUPTFB, COUPTFII}, POU5F1 (POU class 5 homeobox 1) [NCBI Gene 5460] {aka OCT3, OCT4, OCT4Borf1, OTF-3, OTF3, OTF4}, SOX2 (SRY-box transcription factor 2) [NCBI Gene 6657] {aka ANOP3, MCOPS3}, MYC (MYC proto-oncogene, bHLH transcription factor) [NCBI Gene 4609] {aka MRTL, MYCC, bHLHe39, c-Myc}, NANOG (Nanog homeobox) [NCBI Gene 79923], AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, AGR2 (anterior gradient 2, protein disulphide isomerase family member) [NCBI Gene 10551] {aka AG-2, AG2, GOB-4, HAG-2, HEL-S-116, HPC8}, 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}, GAPDH (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 2597] {aka G3PD, GAPD, HEL-S-162eP}, MIR302A (microRNA 302a) [NCBI Gene 407028] {aka MIRN302, MIRN302A, hsa-mir-302, mir-302a}
- **Diseases:** squamous carcinoma (MESH:D002294), Cytotoxicity (MESH:D064420), tumorigenesis (MESH:D063646), Tumor (MESH:D009369), MR (MESH:D008944), neuroblastoma (MESH:D009447), breast cancer (MESH:D001943)
- **Chemicals:** penicillin (MESH:D010406), Agarose (MESH:D012685), water (MESH:D014867), argon (MESH:D001128), paraformaldehyde (MESH:C003043), EDTA (MESH:D004492), LP (MESH:D008070), amphotericin B (MESH:D000666), Glutamax (MESH:C054122), NAHCO3 (MESH:D017693), CO2 (MESH:D002245), DMEM (-), Lipids (MESH:D008055), DPPC (MESH:D015060), gold (MESH:D006046), Chloroform (MESH:D002725), streptomycin (MESH:D013307), MTT (MESH:C070243), DAPI (MESH:C007293), DOTAP (MESH:C070046), ethidium-bromide (MESH:D004996), DMSO (MESH:D004121), phosphatidylcholine (MESH:D010713), pyruvate (MESH:D019289), PBS (MESH:D007854), phorbol ester (MESH:D010703), ammonium sulfate (MESH:D000645), Cholesterol (MESH:D002784), glucose (MESH:D005947)
- **Species:** Homo sapiens (human, species) [taxon 9606], Glycine max (soybean, species) [taxon 3847]
- **Cell lines:** S1939 — Homo sapiens (Human), Galactosialidosis, Induced pluripotent stem cell (CVCL_A3VF), K562 — Homo sapiens (Human), Blast phase chronic myelogenous leukemia, BCR-ABL1 positive, Cancer cell line (CVCL_0004)

## Full text

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## Figures

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## References

38 references — full list in the complete paper: https://tomesphere.com/paper/PMC11829158/full.md

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Source: https://tomesphere.com/paper/PMC11829158