Mutations and alterations in the expression of VEGFA, KRAS, and NFE2L2 oncogenes play a key role in cancer initiation and progression. These genes are enrolled not only in cell proliferation control, but also in angiogenesis, drug resistance, metastasis, and survival of tumor cells. MicroRNAs (miRNAs) are small, non-coding regulatory RNA molecules that can regulate post-transcriptional expression of multiple target genes. We aimed to investigate if miRNAs hsa-miR-17-5p, hsa-miR-140-5p, and hsa-miR-874-3p could interfere in VEGFA, KRAS, and NFE2L2 expression in cell lines derived from head and neck cancer (HNC). FADU (pharyngeal cancer) and HN13 (oral cavity cancer) cell lines were transfected with miR-17-5p, miR-140-5p, and miR-874-3p microRNA mimics. RNA and protein expression analyses revealed that miR-17-5p, miR-140-5p and miR-874-3p overexpression led to a downregulation of VEGFA, KRAS, and NFE2L2 gene expression in both cell lines analyzed. Taken together, our results provide evidence for the establishment of new biomarkers in the diagnosis and treatment of HNC.

Chronic myeloid leukemia (CML) is a stem cell derived malignant disorder result of translocation t(9;22)(q34;q11) called Philadelphia chromosome (Ph⁺). microRNAS (miRNAs) are involved in several biological processes, altering the progression of various pathologies, including CML. This study evaluated whether circulating miRNAs display differential expression profiles in peripheral blood of CML-Chronic Phase (CML-CP) patients newly diagnosed in comparison with CML-CP treated with imatinib. We obtained peripheral blood samples from CML-CP Ph⁺ patients divided among group 1 (untreated newly diagnosed) and group 2 (treated with imatinib). A pool of total leukocytes from healthy donors was considered as control group. Expression analyses were performed for 768 miRNAs by RT-qPCR array. Bioinformatic tools were used to identify significant pathways and interaction networks. We found 80 deregulated miRNAs between the groups and, according to bioinformatic analysis, they are involved in different pathways, including molecular mechanisms of cancer. The study allows better understanding of disease molecular behavior, and it is useful for possible monitoring CML treatment and prognostic biomarkers identification.

Cancer biologists have focused on studying cancer stem cells (CSCs) because of their ability to self-renew and recapitulate tumor heterogeneity, which increases their resistance to chemotherapy and is associated with cancer relapse. Here, we used two approaches to isolate CSCs: the first involved the metabolic enzyme aldehyde dehydrogenase ALDH, and the second involved the three cell surface markers CD44, CD117, and CD133. ALDH cells showed a higher zinc finger E-box binding homeobox 1 (ZEB1) microRNA (miRNA) expression than CD44/CD117/133 triple-positive cells, which overexpressed miRNA 200c-3p: a well-known microRNA ZEB1 inhibitor. We found that ZEB1 inhibition was driven by miR-101-3p, miR-139-5p, miR-144-3p, miR-199b-5p, and miR-200c-3p and that the FaDu Cell Line inhibition occurred at the mRNA level, whereas HN13 did not affect mRNA expression but decreased protein levels. Furthermore, we demonstrated the ability of the ZEB1 inhibitor miRNAs to modulate CSC-related genes, such as TrkB, ALDH, NANOG, and HIF1A, using transfection technology. We showed that ALDH was upregulated upon ZEB1-suppressed miRNA transfection (Mann–Whitney ** p₁₀₁ = 0.009, t-test ** p₁₃₉ = 0.009, t-test ** p₁₄₄ = 0.002, and t-test *** p₁₉₉ = 0.0006). Overall, our study enabled an improved understanding of the role of ZEB1-suppressed miRNAs in CSC biology.

Head and neck cancer (HNC) is one of the most common types of cancer in the world, characterized by resistance to conventional therapies and an unfavorable prognosis due to the presence of tumor stem cells (TSCs). TSCs are cell subpopulations with high potential for invasion, migration, and metastasis, being responsible for the initiation and dissemination of cancer. This study aimed to evaluate the efficacy of treatments with cetuximab and paclitaxel, alone and in combination, in TSCs from oral cavity (SCC-28) and hypopharynx (FADU) cancer cell lines. In addition, the influence of the gene and protein expression of EGFR, NTRK2 (TRKB), KRAS, and HIF-1α on the response to treatments was investigated. TSCs were identified based on ALDH staining, and cell viability assays (MTS) indicated that both TSCs and non-TSCs showed resistance to cetuximab monotherapy, while paclitaxel, either alone or in combination with cetuximab, was more effective in reducing cell viability. Real-time PCR and Western blot analysis revealed increased expression of KRAS and HIF-1α in TSCs, suggesting their possible association with treatment resistance. The results of this study point to specific molecular factors that influence therapeutic responses in HNC, with an emphasis on the efficacy of drug combinations to overcome TSC resistance. The identification of these molecular mechanisms may provide guidelines for the development of more targeted and effective therapies against HNC, improving clinical management and patient prognoses.

Chronic myelogenous leukemia (CML) is a chronic clonal myeloproliferative disease characterized by left leukocytosis, splenomegaly, and the presence of the Philadelphia (Ph) chromosome, which results from the reciprocal and balanced translocation between the long arms of chromosomes 9q34 and 22q11, generating the hybrid protein BCR-ABL, with increased tyrosine kinase activity. The BCR-ABL protein is present in all patients with CML, and its hyperactivity triggers the release of effectors of cell proliferation and inhibitors of apoptosis, and its activity is responsible for the initial oncogenesis of CML. This chapter will review CML from its discovery, molecular and epigenetic mechanisms of disease progression to current treatments.