HN1 is a novel dedifferentiation factor involved in regulating the cell cycle and microtubules in SH-SY5Y neuroblastoma cells.

Hematological and neurological expressed 1 (HN1), encoding a small protein, has been recently explored in different cancers owing to its higher expression in tumor samples as compared to adjacent normal. It was discovered and subsequently named because of its higher expression in hematological and neurological tissues in developing mice. Following discovery, it was considered a neuronal regeneration or dedifferentiation-related gene. However, since then, it has not been characterized in neuroblastoma or differentiated neurons. SH-SY5Y cell line presents a unique model of neuroblastoma often utilized in neurobiology research. In this study, first, we employed bioinformatics analysis along with in vitro evaluation using normal and retinoic acid (RA)-differentiated SH-SY5Y cells to determine the responses of HN1 and its function. The analysis revealed that HN1 expression is higher in neuroblastoma and lower in differentiated neurons and Parkinson's disease as compared to appropriate controls. Since HN1 coexpression network in neuroblastoma is found to be enriched in cell-cycle-related pathways, we have shown that HN1 expression increases in S-phase and remains lower in the rest of the cell cycle phases. Moreover, HN1 expression is also correlated with the microtubule stability in SH-SY5Y cells, which was investigated with nocodazole and taxol treatments. HN1 overexpression increased the ratio of S-type cells (undifferentiated), indicating that it acts as a dedifferentiating factor in neuroblastoma cells. Moreover, cell cycle dynamics also changed upon HN1 overexpression with alternating effects on SH-SY5Y and RA-differentiated (N-type) cells. Therefore, HN1 is a potential cell cycle regulatory element in the development of neuroblastoma or dedifferentiation of neurons, which requires further studies to decipher its mechanistic role.

Mitotic kinase inhibitors as Therapeutic Interventions for Prostate Cancer: Evidence from In vitro Studies.

Prostate cancer is one of the devastating diseases characterized by genetic changes leading to uncontrolled growth and metastasis of the cells of the prostate gland and affects men worldwide. Conventional hormonal and chemotherapeutic agents are effective in mitigating the disease if diagnosed at an early stage. All dividing eukaryotic cells require mitotic progression for the maintenance of genomic integrity in progeny populations. The protein kinases, upon activation and de-activation in an ordered fashion, lead to spatial and temporal regulation of the cell division process. The entry into mitosis along with the progression into sub-phases of mitosis is ensured due to the activity of mitotic kinases. These kinases include Polo-Like-Kinase 1 (PLK1), Aurora kinases, and Cyclin-Dependent-Kinase 1 (CDK1), among others. The mitotic kinases, among others, are usually overexpressed in many cancers and can be targeted using small molecule inhibitors to reduce the effects of these regulators on mechanisms, such as regulation of genomic integrity and mitotic fidelity. In this review, we attempted to discuss the appropriate functions of mitotic kinases revealed through cell culture studies and the impact of their respective inhibitors derived in pre-clinical studies. The review is designed to elucidate the growing field of small molecule inhibitors and their functional screening or mode of action at the cellular and molecular level in the context of Prostate Cancer. Therefore, studies performed specifically on cells of Prostatic-origin are narrated in this review, culminating in a comprehensive view of the specific field of mitotic kinases that can be targeted for therapy of Prostate cancer.