Upregulated miRNAs on the TP53 and RB1 Binding Seedless Regions in High-Risk HPV-Associated Penile Cancer.

Cancer development by the human papillomavirus (HPV) infection can occur through the canonical HPV/p53/RB1 pathway mediated by the E2/E6/E7 viral oncoproteins. During the transformation process, HPV inserts its genetic material into host Integration Sites (IS), affecting coding genes and miRNAs. In penile cancer (PeCa) there is limited data on the miRNAs that regulate mRNA targets associated with HPV, such as the TP53 and RB1 genes. Considering the high frequency of HPV infection in PeCa patients in Northeast Brazil, global miRNA expression profiling was performed in high-risk HPV-associated PeCa that presented with TP53 and RB1 mRNA downregulated expression. The miRNA expression profile of 22 PeCa tissue samples and five non-tumor penile tissues showed 507 differentially expressed miRNAs: 494 downregulated and 13 upregulated (let-7a-5p, miR-130a-3p, miR-142-3p, miR-15b-5p miR-16-5p, miR-200c-3p, miR-205-5p, miR-21-5p, miR-223-3p, miR-22-3p, miR-25-3p, miR-31-5p and miR-93-5p), of which 11 were identified to be in HPV16-IS and targeting TP53 and RB1 genes. One hundred and thirty-one and 490 miRNA binding sites were observed for TP53 and RB1, respectively, most of which were in seedless regions. These findings suggest that up-regulation of miRNA expression can directly repress TP53 and RB1 expression by their binding sites in the non-canonical seedless regions.

Small benzothiazole molecule induces apoptosis and prevents metastasis through DNA interaction and c-MYC gene supression in diffuse-type gastric adenocarcinoma cell line.

Chemo-resistance has been reported as a relevant barrier for the efficiency of gastric cancer treatment. Therefore, the development of effective and safe drugs for cancer chemotherapy is still a challenge. The purpose of this study was to evaluate the anticancer potential of (E)-2-(((2-(benzo[d]thiazo-2-yl)hydrazono)methyl)-4-nitrophenol) (AFN01) against gastric cancer cell lines. Our results showed promising anticancer activity against gastric cancer cells ACP-02 (IC50 = 1.0 µM) and mild activity against other cell lines including non-malignant gastric cell MNP-01 (IC50 = 3.4 µM). This compound significantly induced S phase cell cycle arrest, prevented cell migration and triggered apoptosis in a concentration-dependent manner. Moreover, AFN01 was significantly more genotoxic against tumoral cell ACP-02, when compared to non-malignant cells, such as MNP-01 and healthy peripheral mononuclear blood cells. AFN01 also synergistically interacts with doxorubicin suppressing cell proliferation and c-MYC gene expression in gastric cancer cell line model, with remarkable c-MYC overexpression. Although further pre-clinical and clinical studies are required to explore its safety and efficiency, AFN01 may represent a promising lead anticancer agent for the treatment of gastric cancer.