ALKBH overexpression in head and neck cancer: potential target for novel anticancer therapy

The nine identified human homologues of E. coli AlkB 2-oxoglutarate (2OG) and Fe(II)-dependent dioxygenase, ALKBH1-8 and FTO, display different substrate specificities and diverse biological functions. Here we discovered the combined overexpression of members of the ALKBH family in head and neck squamous cell carcinomas (HNSCC). We found direct correlation of ALKBH3 and FTO expression with primary HNSCC tumor size. We observed unidentified thus far cytoplasmic localization of ALKBH2 and 5 in HNSCC, suggesting abnormal role(s) of ALKBH proteins in cancer. Further, high expression of ALKBHs was observed not only in HNSCC, but also in several cancerous cell lines and silencing ALKBH expression in HeLa cancer cells resulted in dramatically decreased survival. considering the discovered impact of high expression of ALKBH proteins on HNSCC development, we screened for ALKBH blockers among newly synthetized anthraquinone derivatives and demonstrated their potential to support standard anticancer therapy

The expression of MMP-14 and microRNA-410 in FFPE tissues of human endometrial adenocarcinoma

Endometrial cancer (EC) is the most common gynecological malignancy in Europe and North America. It is classified into two types exhibiting different characteristics and prognosis. Type I is an estrogen-dependent tumor, histologically classified as low grade and low stage, usually with an excellent prognosis. Type II EC is unrelated to estrogen stimulation and is characterized by a poor prognosis. MicroRNAs (miRNAs, miRs) are small non-coding RNA polynucleotides that regulate gene expression posttranscriptionally. Various dysregulations in microRNA expression are often considered to have an impact on the diagnosis, prognosis and overall survival in patients diagnosed with different types of cancers. Recent data suggest that microRNAs play an important role in the pathogenesis of EC. The aim of the study was to evaluate the involvement of matrix metaloprotease 14 (MMP-14) and microRNA-410 in formation of the EC tumor. To this end expression of MMP-14 and microRNA-410 was assessed within the cancer, transient and healthy zones in the histological sections of tumours using immunohistochemical staining and laser capture microdissection (LCM) followed by a quantitative real-time PCR. The results revealed significantly higher expression of MMP14 in the cancer tissue zone in comparison to the healthy tissue zone, as well as a lower expression of microRNA410 in the cancer zone compared with the healthy zone. This reverse correlation may suggest a regulatory role of miRNA-410 in modulating levels of MMP-14 in EC. This is the first report on such regulation in human endometrial cancer