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Updated: Jan 20, 2026
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Modulation of all-trans retinoic acid-induced MiRNA expression in neoplastic cell lines: a systematic review
Lara Lima1,2, Thaísa Cristina Tavares de Melo2, Diego Marques2
1Postgraduate Program in Nutrition, Federal University of Rio Grande do Norte, Natal, Brazil.
Background:
Cancer is a genetic and epigenetic disease that involves inactivation of tumor suppressor genes and activation of proto-oncogenes. All-trans retinoic acid (ATRA) is an isomer of retinoic acid involved in the onset of differentiation and apoptosis of a number of normal and cancer cells, functioning as an anti-cancer agent in several neoplasms. Ectopic changes in the expression of certain microRNAs (miRNAs) occur in response to ATRA, leading to phenotypic alterations in neoplastic cell lines. Moreover, the modulation of miRNA patterns upon ATRA-treatment may represent an effective chemopreventive and anti-cancer therapy strategy. The present systematic review was performed to provide an overview of the modulation of ATRA-induced miRNA expression in different types of neoplastic cells and identify the efficacy of intervention factors (i.e., concentration and duration of treatment) and how they influence expression profiles of oncogenesis-targeting miRNAs.
Methods:
A systematic search was conducted according to the PRISMA statement via the US National Library of Medicine MEDLINE/PubMed bibliographic search engine.
Results:
The search identified 31 experimental studies involving human cell lines from nine different cancer types (neuroblastoma, acute myeloid leukemia, breast cancer, lung cancer, pancreatic cancer, glioma, glioblastoma, embryonal carcinoma, and colorectal cancer) treated with ATRA at concentrations ranging from 10- 3 μmol/L to 102 μmol mol/L for 24 h to 21 days.
Conclusion:
The concentrations used and the duration of treatment of cancer cells with ATRA varied widely. The presence of ATRA in the culture medium of cancer cells was able to modulate the expression of more than 300 miRNAs, and inhibit invasive behavior and deregulated growth of cancer cells, resulting in total tumor remission in some cases. ATRA may thus be broadly effective for neoplasm treatment and prevention, although these studies may not accurately represent in vivo conditions. Additional studies are required to elucidate ATRA-induced miRNA modulation during neoplasm treatment.
Insights
All-trans retinoic acid (ATRA) alters microRNA (miRNA) expression in cancer cells, inhibiting growth and promoting remission. This review highlights ATRA
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Cancer is a genetic and epigenetic disease driven by altered gene expression.
- All-trans retinoic acid (ATRA) exhibits anti-cancer properties by inducing differentiation and apoptosis.
- MicroRNAs (miRNAs) play crucial roles in cancer development and can be modulated by ATRA.
Purpose of the Study:
- To systematically review how ATRA influences miRNA expression in various cancer cell types.
- To identify effective intervention factors (concentration, duration) for ATRA-induced miRNA modulation.
- To assess the impact of ATRA on miRNA profiles targeting oncogenesis.
Main Methods:
- A systematic literature search was performed using the MEDLINE/PubMed database.
- Studies adhering to the PRISMA statement were included.
- Analysis focused on experimental studies involving ATRA treatment of human cancer cell lines.
Main Results:
- 31 studies utilized ATRA on nine distinct cancer types (e.g., neuroblastoma, leukemia, breast, lung, pancreatic, glioma, colorectal).
- ATRA treatment varied in concentration (10^-3 to 10^2 μmol/L) and duration (24 hours to 21 days).
- ATRA modulated over 300 miRNAs, inhibited cancer cell invasion and growth, and led to tumor remission in some cases.
Conclusions:
- ATRA effectively modulates miRNA expression and inhibits cancer cell proliferation across diverse cancer types.
- Varied ATRA concentrations and treatment durations were observed, influencing miRNA profiles.
- While promising for cancer treatment and prevention, further in vivo studies are needed to confirm ATRA's efficacy and mechanisms.
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