Role of stem cell proteins and microRNAs in embryogenesis and germ cell cancer.

Embryonic stem (ES) cells are pluripotent cells derived from the inner cell mass of the blastocyst. These cells can proliferate indefinitely and differentiate into all cell lineages. Germ cell cancers (GCC) mimic embryonic development to a certain extent. The origin of GCC trace back to primordial germ cells/gonocytes in the embryo, which determines their specific characteristics such as totipotency and overall (exceptional) sensitivity to DNA damaging agents. Thus GCC provide a useful model system for the study of gene regulation involved in oncogenesis as well as development. Several reports have demonstrated the role of specific proteins and microRNAs (miRs) in the control of pluripotency and thus early development. miRs are small non-coding RNA molecules that post-transcriptionally regulate gene expression by base-paring to protein encoding mRNAs. miRs are predicted to regulate up to 30% of the protein-encoding genes within the human genome. They are expressed in a tissue-specific and developmentally regulated manner. Aberrant miR expression and its correlation with development and progression of cancers is an emerging field. Important evidences have shown that knock-down by synthetic anti-sense oligonucleotides or re-expression of specific miRs by pre-miR can induce drug sensitivity, leading to increased inhibition of cancer cell growth, invasion, and metastasis. In addition, miRs have been found in body fluids of patients with different types of diseases, including cancer. Therefore, investigation of miRs can shed light on the process of pathogenesis, and may provide biomarkers for diagnosis and prognosis. A subset of miRs is specifically expressed in ES cells and GCC, suggesting their critical role in early embryogenesis and development. In this review we discuss the current view of the biology of embryonic stem cell proteins and miRs in GCC, and their potential clinical impact.