Regulatory changes occurring early in colorectal cancer development remain poorly investigated. Since the majority of cases develop from polyps in the adenoma-carcinoma transition, a search of early molecular features, such as aberrations in miRNA expression occurring prior to cancer development, would enable identification of potentially causal, rather than consequential, candidates in the progression of polyp to cancer. In the current study, by employing small RNA-seq profiling of colon biopsy samples, we described differentially expressed miRNAs and their isoforms in the adenoma-carcinoma transition. Analysis of healthy-adenoma-carcinoma sequence in an independent validation group enabled us to identify early deregulated miRNAs including hsa-miR-1246 and hsa-miR-215-5p, the expressions of which are, respectively, gradually increasing and decreasing. Loss-of-function experiments revealed that inhibition of hsa-miR-1246 lead to reduced cell viability, colony formation, and migration rate, thereby indicating an oncogenic effect of this miRNA in vitro. Subsequent western blot and luciferase reporter assay provided evidence of hsa-miR-1246 being involved in the regulation of target AXIN2 and CFTR genes’ expression. To conclude, the present study revealed possible involvement of hsa-miR-1246 in early colorectal cancer development and regulation of tumor suppressors AXIN2 and CFTR.

Deregulated microRNA (miRNA) expression profiles and their contribution to carcinogenesis have been observed in virtually all types of human cancer. However, their role in the pathogenesis of rare mesenchymal gastrointestinal stromal tumors (GISTs) is not well defined, yet. In this study, we aimed to investigate the role of two miRNAs strongly downregulated in GIST—miR-375-3p and miR-200b-3p—in the pathogenesis of GIST. To achieve this, miRNA mimics were transfected into GIST-T1 cells and changes in the potential target gene mRNA and protein expression, as well as alterations in cell viability, migration, apoptotic cell counts and direct miRNA–target interaction, were evaluated. Results revealed that overexpression of miR-375-3p downregulated the expression of KIT mRNA and protein by direct binding to KIT 3′UTR, reduced GIST cell viability and migration rates. MiR-200b-3p lowered expression of ETV1 protein, directly targeted and lowered expression of EGFR mRNA and protein, and negatively affected cell migration rates. To conclude, the present study identified that miR-375-3p and miR-200b-3p have a tumor-suppressive role in GIST.

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Background Ulcerative Colitis (UC) is a chronic, relapsing inflammatory disease of the lower gastrointestinal tract. The frequency of UC is increasing worldwide, however, existing methods for both diagnostics and treatment of this disease are not efficient enough. It is known that besides comprised immune response, environmental and genetic factors, gut microbiota play a major role in the onset and course of UC. Therefore, efforts are currently being made to find and develop new gut microbiome-based tools to improve the management of UC. The aim of this study was to identify changes in the gut microbiome during active and quiescent UC. Methods Study included 72 subjects, who were divided into three age- and sex-matched groups: control (n=25), active UC (n=27) and quiescent UC (n=20). Total DNA was extracted from faeces, which was further subjected to the next generation sequencing of 16S rRNA-coding gene V1-V2 hypervariable region on MiSeq (Illumina) platform. Further, bioinformatics and statistical analysis were performed. Results Bacterial α-diversity, as assessed by Richness, Shannon and Simpson diversity indexes, revealed that control patients had highest α-diversity compared to patients with active UC or quiescent UC (p<0.05), but there were no differences between UC disease states (p>0.05). Significant microbial community clusters (β-diversity), as assessed by the Bray-Curtis dissimilarity index, were identified between control subjects and patients with active or quiescent UC (p=0.02, p<0.01, respectively). However, no significant clusters were found between different disease states (p=0.22). In-between samples dissimilarity assessed by Bray-Curtis dissimilarity index showed that samples from control subjects had higher in-between sample similarity (mean 0.542 ± 0.117) than patients with active (mean 0.638 ± 0.161) and quiescent (0.6 ± 0.145) UC. In addition, 16, 13 and 27 core taxa were identified in active, quiescent UC and control group, respectively. Differential abundance of Cuneatibacter, Faecalibacterium and Prevotellamassilia genera was detected when comparing control vs UC (both active and quiescent), Paraprevotella and Cuneatibacter genera – control vs active UC, Faecalibacterium, Prevotellamassilia, Mediterraneibacter and Cuneatibacter genera – control vs quiescent UC. Conclusion In conclusion, this study revealed both qualitative and quantitative gut microbiota changes in active and quiescent UC. Study was funded by the Research Council of Lithuania (Grant No. S-MIP-20-56).

We report a case of a patient with the BRCA1 5382insC mutation in the location 17q21. The patient was referred for genetic counseling because of infertility. While consulting the patient for infertility and collecting the family tree, the patient told that her mother, grandmother and aunt had or still have ovarian cancer. So the patient received a genetic test for six most often BRCA1 and BRCA2 gene mutations. The test showed that the patient had the mutation of BRCA1 5382insC gene. The BRCA1 5382insC mutation increases the risk of getting breast cancer 10 times and ovarian cancer 20 times, compared with the general population. To reduce the risk of breast and ovarian cancer the patient received advices on healthy life style, screening tests for ovarian cancer and was offered to consult an oncologist about prophylactic oophorectomy.