KIF18B promotes the proliferation of pancreatic ductal adenocarcinoma via activating the expression of CDCA8

Abstract

Pancreatic cancer is one of the malignant tumors with the worst prognosis, and the 5-year survival rate of this disease is less than 1%. About 90% of pancreatic cancer is pancreatic ductal adenocarcinoma (PDAC), and targeting therapy has become a promising treatment for PDAC in recent years. To improve the survival rate, novel therapeutic targets for PDAC are still urgently needed. KIF18B was initially identified as a member of the kinesin family and involved in multiple cellular processes, such as separation of chromosomes in mitosis. Recently, it was found that KIF18B was involved in the growth and development of multiple cancers. However, the potential link between KIF18B and PDAC is still unclear. In this study, we demonstrated that KIF18B was highly expressed in human PDAC tissues, and related with the poor prognosis and clinical features, such as tumor size (*p = .013) and pTNM stage (*p = .025), of patients with PDAC. We further found that KIF18B knockdown blocked the cell proliferation of PDAC in vitro and in vivo, and the cell cycle was arrested caused by KIF18B depletion. Additionally, we also found that KIF18B bound to the promoter region of the cell division cycle associated 8 and thus activated its transcription. Taken together, this study explored the molecular mechanism underlying KIF18B promoting PDAC and provided a novel therapeutic target of this disease. K E Y W O R D SCDCA8, KIF18B, pancreatic ductal adenocarcinoma, proliferation, therapeutic target

The diagnostic and prognostic value of cell division cycle associated gene family in Hepatocellular Carcinoma

“…CDCA8 was also considered as an oncogene [22] in several types of cancers such as breast cancer [14], bladder cancer [23] and cutaneous melanoma [24]. The resent two studies and we all indicated that the mRNA level of CDCA8 was up-regulated in HCC and was associated with poor survival.…”

Laminin‑332 mediates proliferation, apoptosis, invasion, migration and epithelial‑to‑mesenchymal transition in pancreatic ductal adenocarcinoma

“…It has been reported that ~50% of patients have been confirmed to possess metastasized cancer cells (3). Despite continuous improvements in diagnosis and treatment, this type of cancer is almost invariably fatal, and the 5-year survival rate of patients is ~8% (4,5). PDAC has a high degree of malignant biological characteristics, including invasion and metastasis, which leads to a poor prognosis.…”

Analysis of KIF2C, 4A, 10, 11, 14, 18B, 20A, and 23 in HCC and their clinical significance as new-born prognostic markers of HCC

“…KIF18B belongs to the kinesin 8 subfamily and is involved in the separation of chromosomes and spindle localization during mitosis [55]. In recent years, investigations have shown that KIF18B participates in the growth and development of a variety of cancers [11,56]. Per Li et al, KIF18B expression is regulated in a cell cycle-dependent manner and, therefore, could be involved in the regulation of cell cycle and cell proliferation [11].…”

“…In recent years, investigations have shown that KIF18B participates in the growth and development of a variety of cancers [11,56]. Per Li et al, KIF18B expression is regulated in a cell cycle-dependent manner and, therefore, could be involved in the regulation of cell cycle and cell proliferation [11]. Our analysis results revealed that KIF18B is an important regulator of HCC prognosis and is closely connected to cell cycle and DNA replication-related pathways, which provides ideas and strategies for our next focus on the role of KIF18B in HCC.…”

“…During mitosis in eukaryotes, the abnormal expression of kinesin can cause chromosome super-condensation, abnormal spindle formation, abnormal cytokinesis, aneuploidy, and other conditions, which can result in an uneven distribution of genetic material and defects in daughter cells and may lead to the development of cancer. Many studies have shown that the abnormal expression of kinesin is related to a variety of human malignancies, including lung cancer [7][8][9], breast cancer [10], pancreatic cancer [11], kidney cancer [12], and colorectal cancer [13].…”