Furthermore, PKR expression was increased in precancerous stages of mammary cell hyperplasia and dysplasia compared to normal tissues, indicating that PKR expression may be upregulated by the process of tumorigenesis.
This study is the first intense characterization of pre-miR-886 as well as the initial report on its function as a PKR regulator, which suggests a critical role in tumorigenesis.
In recent studies, PKR has been shown to be an important participant in a broad array of cellular processes, including signal transduction, differentiation, apoptosis, cell growth, and tumorigenesis.
Because most neoplastic cells are resistant to certain apoptotic cues, we reasoned that an early molecular event in carcinogenesis or leukemogenesis might be the inactivation of PKR by expression or activation of intracellular PKR inhibitors.
These results suggest that follicular cells newly express PKR during thyroid carcinogenesis, that PKR is more expressed in papillary carcinoma than in nonpapillary carcinoma, that PKR expression may be associated with high vascular invasion and satellite nodules, and that PKR expression is linked to low cell proliferative activity.
The topics covered include the significance of the regulation and overexpression of polypeptide chain initiation factors for cell transformation and malignancy, the role of mRNA structure in the control of synthesis of key growth regulatory proteins, the actions of the eIF2 alpha-specific protein kinase PKR in the control cell growth and apoptosis, and the involvement of the elongation factor eEF1 in oncogenesis.