Modulation of all-trans retinoic acid-induced MiRNA expression in neoplastic cell lines: a systematic review

• Published in: BMC cancer Vol. 19; no. 1; p. 866
• Main Authors: Lima, Lara, de Melo, Thaísa Cristina Tavares, Marques, Diego, de Araújo, Jéssica Nayara Góes, Leite, Isabela Samária Fernandes, Alves, Camila Xavier, Genre, Julieta, Silbiger, Vivian Nogueira
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 30.08.2019; BioMed Central; BMC
• Subjects: Acute myelocytic leukemia; All-trans retinoic acid; Antineoplastic agents; Apoptosis; Breast cancer; Cancer; Cancer cells; Cancer prevention; Cancer treatment; Carcinogenesis; Carcinoma; Care and treatment; Cell Line, Tumor; Cell Movement - drug effects; Cell Proliferation - drug effects; Cells (Biology); Colorectal cancer; Epigenetic inheritance; Expression modulation; Gene expression; Gene Expression Regulation, Neoplastic - drug effects; Genes; Genetic aspects; Glioblastomas; Gliomas; Humans; Leukemia; Lung cancer; MicroRNA; MicroRNAs - genetics; miRNA; Myeloid leukemia; Neoplasms - drug therapy; Neoplasms - genetics; Neuroblastoma; Pancreatic cancer; Time Factors; Tretinoin; Tretinoin - pharmacology; Tumors; miRNA; All-trans retinoic acid; Expression modulation; Cancer
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-019-6081-7

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. A systematic search was conducted according to the PRISMA statement via the US National Library of Medicine MEDLINE/PubMed bibliographic search engine. 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  μmol/L to 10  μmol mol/L for 24 h to 21 days. 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.