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Kelch-like family member 21 (KLHL21) is involved in cell mitosis and motility. Nevertheless, the clinical significance and biological function of KLHL21 in cholangiocarcinoma (CCA) are elusive. This is the first study to describe a pivotal role for KLHL21 in the progression of CCA. The expression of KLHL21 was elevated in CCA tissues compared with paired normal bile duct tissues. In addition, immunohistochemical and statistical analyses demonstrated that the expression of KLHL21 correlated inversely with tumor histological grade (p < 0.05) and the overall survival of patients (p < 0.01). In CCA cells, we found that the inhibition of KLHL21 significantly reduced proliferation, migration and invasion. Further results indicated that inhibition of KLHL21 triggered G0/G1 cell cycle arrest, leading to the increased expression of P21 and P27 and decreased expression of Cyclin E1, which eventually resulted in proliferation suppression in CCA cells. Furthermore, KLHL21 knockdown alleviated the activation of the Erk signaling pathway via decreasing the expression of phospho-Erk1/2. Our data demonstrated that KLHL21 plays an essential role in the tumorigenesis and progression of CCA, implying that it might serve as a potential therapeutic target for CCA treatment. [ABSTRACT FROM AUTHOR]

As the sixth most prevalent cancer, hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. Human replication protein A (RPA), a three-subunit protein, plays a central role in eukaryotic DNA replication, homologous recombination, and excision repair, including RPA1, RPA2 and RPA3. Recently, some studies focusing on the relation between RPA1 and carcinogenesis have demonstrated that RPA1 is a candidate oncogene and influences tumor biological behaviors in many cancers such as esophageal carcinoma, colon cancer, urothelial carcinomas, etc. However, the characteristic role of RPA1 in HCC and the detailed potential mechanism remain unknown. To identify the real effects of RPA1 on HCC and its potential pathway participating in the changes of liver cancer cells, we have conducted this study and demonstrated that RPA1 is up-regulated both in liver cancer cell lines and HCC tissues, which is associated with poorer prognosis, advanced TNM stage and larger tumor size. Stable knock-down of RPA1 by specific small hairpin RNA (shRNA) contributes to the impaired proliferate ability of SK-HEP-1 cells both in vitro and vivo. Consistently, upregulation of RPA1 in HuH-7 cells by specific adenovirus promotes tumor cells' proliferation. Furthermore, cyclin-dependent-kinase 4(CDK4)/Cyclin-D pathway is found to be well associated with RPA1 induced proliferation. In conclusion, RPA1 plays a pivotal role as a potential oncogene in HCC and promotes tumor proliferation via CDK4/Cyclin-D pathway. [ABSTRACT FROM AUTHOR]