CCNI2 knockdown inhibits the proliferation, apoptosis and migration of pancreatic cancer cells

Background: Pancreatic cancer has been recognized as one of the most serious malignant tumors in the world, and its molecular mechanism is still not fully understood. Cyclin I-like (CCNI2) is a homolog of Cyclin I (CCNI), and at present its function is largely unknown. Methods: In this study, we aimed to explore the role of CCNI2 in the development of pancreatic cancer. The expression levels of CCNI2 in pancreatic cancer tissues and cells were detected by immunohistochemical analysis and qPCR, respectively. Lentivirus was used to deliver shRNA to pancreatic cancer cells to construct CCNI2 knockdown cell models. MTT and colony formation assays were used to assess cell proliferation capacity, flow cytometry was used to detect apoptosis, wound-healing and Transwell assays were used to determine cell migration. Results: Our results revealed that CCNI2 is not only highly expressed in pancreatic cancer, but also significantly correlated with pathological grade, pathological stage, and survival rate. It was confirmed that knockdown of CCNI2 inhibited the proliferation and cell migration of pancreatic cancer cells while promoting apoptosis. Furthermore, human apoptotic antibody arrays showed that CCNI2 is involved in apoptosis process by up-regulating the pro-apoptotic proteins. Conclusions: In conclusion, CCNI2 may be a prognostic marker for pancreatic cancer and is associated with its development. Thus, CCNI2 possesses potential to act as a therapeutic target for pancreatic cancer treatment.

CCNI2 knockdown inhibits the proliferation, apoptosis and migration of pancreatic cancer cells

Background: Pancreatic cancer has been recognized as one of the most serious malignant tumors in the world, and its molecular mechanism is still not fully understood. Cyclin I-like (CCNI2) is a homolog of Cyclin I (CCNI), and at present its function is largely unknown.Methods: In this study, we aimed to explore the role of CCNI2 in the development of pancreatic cancer. The expression levels of CCNI2 in pancreatic cancer tissues and cells were detected by immunohistochemical analysis and qPCR, respectively. Lentivirus was used to deliver shRNA to pancreatic cancer cells to construct CCNI2 knockdown cell models. MTT and colony formation assays were used to assess cell proliferation capacity, flow cytometry was used to detect apoptosis, wound-healing and Transwell assays were used to determine cell migration.Results: Our results revealed that CCNI2 is not only highly expressed in pancreatic cancer, but also significantly correlated with pathological grade, pathological stage, and survival rate. It was confirmed that knockdown of CCNI2 inhibited the proliferation and cell migration of pancreatic cancer cells while promoting apoptosis. Furthermore, human apoptotic antibody arrays showed that CCNI2 is involved in apoptosis process by up-regulating the pro-apoptotic proteins.Conclusions: In conclusion, CCNI2 may be a prognostic marker for pancreatic cancer and is associated with its development. Thus, CCNI2 possesses potential to act as a therapeutic target for pancreatic cancer treatment.

Cyclin I-like (CCNI2) is a cyclin-dependent kinase 5 (CDK5) activator and is involved in cell cycle regulation

In contrast to conventional cyclin-dependent kinases that are important for mitotic cell division, cyclin-dependent kinase 5 (CDK5) is predominantly activated in post-mitotic cells and is involved in various cellular events. The kinase activity of CDK5 is tightly regulated by specific activators including p35, p39, and cyclin I (CCNI). Here we show that cyclin I-like (CCNI2), a homolog of CCNI, interacts with CDK5 and activates the kinase activity of CDK5. Different from CCNI, which colocalizes with CDK5 in the nuclei in transfected cells, CCNI2 mainly retains CDK5 in the cytoplasm as well as on the cell membrane. Furthermore, although the expression level of CCNI2 mRNA and CCNI2 protein do not change significantly during cell cycle, depletion of CCNI2 with siRNA affects cell cycle progression as well as cell proliferation. In conclusion, our data strongly suggest that CCNI2 is a novel CDK5 activator and is involved in cell cycle regulation.

Cyclin I and p35 determine the subcellular distribution of Cdk5

The atypical cyclin-dependent kinase 5 (Cdk5) serves an array of different functions in cell biology. Among these are axonal guidance, regulation of intercellular contacts, cell differentiation, and prosurvival signaling. The variance of these functions suggests that Cdk5 activation comes to pass in different cellular compartments. The kinase activity, half-life, and substrate specificity of Cdk5 largely depend on specific activators, such as p25, p35, p39, and cyclin I. We hypothesized that the subcellular distribution of Cdk5 activators also determines the localization of the Cdk5 protein and sets the stage for targeted kinase activity within distinct cellular compartments to suit the varying roles of Cdk5. Cdk5 localization was analyzed in murine kidney and brain slices of wild-type and cyclin I- and/or p35-null mice by immunohistochemistry and in cultured mouse podocytes using immunofluorescence labeling, as well as cell fractionation experiments. The predominance of cyclin I mediates the nuclear localization of Cdk5, whereas the predominance of p35 results in a membranous localization of Cdk5. These findings were further substantiated by overexpression of cyclin I and p35 with altered targeting characteristics in human embryonic kidney 293T cells. These studies reveal that the subcellular localization of Cdk5 is determined by its specific activators. This results in the directed Cdk5 kinase activity in specific cellular compartments dependent on the activator present and allows Cdk5 to serve multiple independent roles.