Growing evidence suggests that microRNAs are involved in the development and progression of colorectal cancer (CRC). In the present study, deregulation and functioning of tumor-suppressive miR-215-5p was evaluated in CRC. In total, 448 tumor tissues and 325 paired adjacent healthy tissues collected from Czech and Spain cohorts of CRC patients have been used for miR-215-5p expression analyses. A series of in vitro experiments have been performed using transient transfection of miR-215-5p mimics into four CRC cell lines to identify specific cellular processes affected by miR-215-5p. Further, the effects of miR-215-5p on tumor growth were evaluated in vivo using NSG mice and stable cell line overexpressing miR-215-5p. Target mRNAs of miR-215-5p were tested using luciferase assay and western blot analyses. We found that miR-215-5p is significantly downregulated in tumor tissues compared with non-tumor adjacent tissues and its decreased levels correlate with the presence of lymph node metastases, tumor stage, and shorter overall survival in CRC patients. Overexpression of miR-215-5p significantly reduced proliferation, clonogenicity, and migration of CRC cells, lead to cell cycle arrest in G2/M phase and p53-dependent induction of apoptosis. The ability of miR-215-5p to inhibit tumor growth was confirmed in vivo. Finally, we confirmed epiregulin and HOXB9 to be the direct targets of miR-215-5p. As epiregulin is EGFR ligand and HOXB9 is its transcriptional inducer, we suggest that the main molecular link between miR-215-5p and CRC cells phenotypes presents the EGFR signaling pathway, which is one of the canonical pathogenic pathways in CRC.

In-depth study of cell cycle proteins and human papillomavirus (HPV) genotyping can provide useful information about the malignant potential of precursor lesions of cervical carcinoma (CC). Immunostaining of cell cycle–related proteins (p16, cyclin D1, Ki-67, p53, and ProEx C) was evaluated using tissue microarrays, and HPV genotypes were identified in 144 cervical tissue specimens encompassing normal or benign epithelial lesions, low- and high-grade squamous intraepithelial lesions (LSIL and HSIL, respectively), and CC. In addition, 14 cases with atypical immature metaplasia (AIM) were included to compare their immunohistochemical features with those of well-established precursor lesions. Expression of p16, Ki-67, and ProEx C was most associated with the severity of dysplasia. Positive expression of p16, Ki-67, and ProEx C and negative expression of p53 seem to be related to HPV-16 infection. AIM cases show an immunohistochemical pattern more similar to LSIL than to HSIL. Immunohistochemical assessment of cell cycle proteins may help to distinguish normal and benign conditions of the cervix from precursor lesions of CC.