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

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.

Histopathological prognosis of papillary thyroid carcinoma associated with nutritional status of vitamins A and E.

BACKGROUND/OBJECTIVES: Experimental and clinical studies have shown that vitamins A and E can inhibit cancer formation and progression. The unfavourable status of these vitamins can represent risk factors for the disease. This study aimed to evaluate the associations between the nutritional status of vitamins A and E (serum levels and dietary intake) and histopathological outcomes in Papillary Thyroid Carcinoma (PTC) patients. SUBJECTS/METHODS: We applied a cross-sectional study (2017-2018) and quantified retinol (ROH) and α-tocopherol (TOH) serum levels and vitamins dietary intake of 46 PTC patients. Serum vitamins were quantified by high efficiency liquid chromatography and vitamins dietary intake was analyzed by 24-hr dietary recalls. RESULTS: Patients with lower ROH serum levels were more likely to present lymph node metastasis and/or angiolymphatic invasion (p = 0.025). In addition, higher vitamin A and vitamin E intake are related to the absence of extrathyroidal extension (p = 0.013) and lymph node metastasis (p = 0.007), respectively. Our findings suggest that a ROH serum level greater than 2.65 µmol/L in PTC patients may be a protective factor against the presence of lymph node metastasis and angiolymphatic invasion. In addition, vitamin A and E intake may protect against extrathyroidal extension and lymph node metastasis. CONCLUSIONS: A favourable nutritional status (higher serum levels and/or intake) of vitamin A and E may be associated with less aggressive tumours in PTC patients.