IRF1 is a transcription factor well known for its role in IFN signaling. Although IRF1 was initially identified for its involvement in inflammatory processes, there is now evidence that it provides a function in carcinogenesis as well. IRF1 has been shown to affect several important antitumor mechanisms, such as induction of apoptosis, cell cycle arrest, remodeling of tumor immune microenvironment, suppression of telomerase activity, suppression of angiogenesis and others. Nevertheless, the opposite effects of IRF1 on tumor growth have also been demonstrated. In particular, the “immune checkpoint” molecule PD-L1, which is responsible for tumor immune evasion, has IRF1 as a major transcriptional regulator. These and several other properties of IRF1, including its proposed association with response and resistance to immunotherapy and several chemotherapeutic drugs, make it a promising object for further research. Numerous mechanisms of IRF1 regulation in cancer have been identified, including genetic, epigenetic, transcriptional, post-transcriptional, and post-translational mechanisms, although their significance for tumor progression remains to be explored. This review will focus on the established tumor-suppressive and tumor-promoting functions of IRF1, as well as the molecular mechanisms of IRF1 regulation identified in various cancers.

Constitutive androstane receptor (CAR, NR1I3), which is under consideration in this review, is a member of the superfamily of nuclear receptors. However, certain features distinguish CAR from the...

Identification of prognostic molecular markers of breast cancer is extremely important. The spreading out of the primary breast tumour cells to the lymphatic system is at the forefront of symbolising the first signs of distant organ metastasis. Deregulated genes in breast cancer tissues that spread to lymph nodes may show early predictive molecular markers. In the present study, we selected five microRNAs, which play a key function in the invasion-metastasis cascade. We investigated the levels of microRNAs in 80 paired samples of BC and matched adjoining tissues, and we examined the potential relationships between microRNA levels and positive lymph node status. Our results attest that three microRNAs (miR-21, miR-155, miR-222) were significantly up-regulated, whilst miR-205 was substantially down-regulated in BC tissues in relation to normal adjoining tissues in a heterogeneous patient cohort. The high levels of two microRNAs, miR-155 and miR-222, showed a statistical relation with the positive lymph node status, especially in patients that had triple negative BC. Conversely, miR-155 was substantially down-regulated in tumour tissues of patients who received preoperative neoadjuvant chemotherapy (NAC) compared with tumour tissues of patients without NAC in cohorts sub-classified to lymph node positive status. Our findings show evidence that the miR-155 and the miR-222 can be defined as molecular markers in regards to cancer patients to prognosticate spread to the lymph node. They also showed that the miR-155 could have crucial significances in BC treatment.

Allelic variants of cytochrome P450: CYP1A1, CYP1A2, CYP19 (aromatase), and the II-phase enzyme sulfotransferase 1A1 (SULT1A1) genes are associated with a high risk of hormone-dependent cancers. We estimated the frequency of these allelic variants in the female population of the Novosibirsk district and their association with the elevated risk of breast cancer. A DNA bank of patients with gynecologic oncology, patients with breast cancer (n=335), and healthy women (n=530) was created, and the following single-nucleotide polymorphisms were examined: CYP1A1 M1 polymorphism, that is, T264-C transition in the 30-noncoding region; CYP1A2*1F polymorphism, that is, C734-A transversion in the CYP1A2 gene; C-T transition (Arg264Cys) in exon 7 of CYP19; and SULT1A1*2 polymorphism, that is, G638-A transition (Arg213His) in the SULT1A1 gene. The results of our study indicate that women with mutant allele C and genotypes C/T, C/C of the CYP1A1 gene, wild-allele C, and genotype C/C of the CYP1A2 gene, mutant allele A and genotypes A/G, A/A of the SULT1A1 gene have an increased risk of development of breast cancer. Women with body mass index ≥30 and the heterozygous genotype C/T of the CYP19 gene have an increased risk of breast cancer. The CYP1A2 heterozygous variant genotype C/A is associated with an increased risk of an estrogen receptor (ER⁺) tumor.