BACKGROUND Hepatocellular carcinoma(HCC)ranks among the most prevalent and deadly malignancies,characterized by a high recurrence rate.Regulator of chromosome condensation 1(RCC1)serves as a principal guanine nucleoti...BACKGROUND Hepatocellular carcinoma(HCC)ranks among the most prevalent and deadly malignancies,characterized by a high recurrence rate.Regulator of chromosome condensation 1(RCC1)serves as a principal guanine nucleotide exchange factor for ras-related nuclear protein guanosine triphosphatase(GTPase)and is implicated in various cancers.However,the role of RCC1 in HCC remains unex-plored.AIM To elucidate the functional significance and molecular mechanisms of RCC1 in HCC.METHODS Bioinformatics were to examine the expression levels of RCC1 in HCC and to assess its impact on the prognosis of this malignancy.The cell counting kit-8 assay and flow cytometry were utilized to evaluate the cell viability and cell cycle of HCC cells.Furthermore,quantitative reverse transcription and immunoblotting were to investigate the influence of RCC1 on cyclin associated proteins.RESULTS Bioinformatics analysis revealed that RCC1 was highly expressed in HCC and correlated with poor prognosis in HCC patients.Functional studies showed that RCC1 overexpression promoted the malignant phenotype of HCC cells,especially the proliferation of HCC cells,whereas RCC1 knockdown had the opposite effect.Mechanistically,we identied cell division cycle-associated(CDCA)8 as a downstream target of RCC1 in HCC.RCC1 overexpression markedly increased CDCA8 levels,consequently enhancing cell proliferation and survival in HCC cells.Additionally,we discovered that RCC1 contributed to the development and progression of HCC by activating the phosphoinositide 3-kinase/protein kinase B/cyclin-dependent kinase inhibitor 1a pathway through CDCA8.CONCLUSION Our study provides profound insights into the pivotal role of RCC1 in HCC and its potential as a therapeutic target.展开更多
基金Supported by the National Natural Science Foundation of China,No.82002940 and No.82203336Shaanxi Natural Science Foundation,No.2023-JC-YB-166.
文摘BACKGROUND Hepatocellular carcinoma(HCC)ranks among the most prevalent and deadly malignancies,characterized by a high recurrence rate.Regulator of chromosome condensation 1(RCC1)serves as a principal guanine nucleotide exchange factor for ras-related nuclear protein guanosine triphosphatase(GTPase)and is implicated in various cancers.However,the role of RCC1 in HCC remains unex-plored.AIM To elucidate the functional significance and molecular mechanisms of RCC1 in HCC.METHODS Bioinformatics were to examine the expression levels of RCC1 in HCC and to assess its impact on the prognosis of this malignancy.The cell counting kit-8 assay and flow cytometry were utilized to evaluate the cell viability and cell cycle of HCC cells.Furthermore,quantitative reverse transcription and immunoblotting were to investigate the influence of RCC1 on cyclin associated proteins.RESULTS Bioinformatics analysis revealed that RCC1 was highly expressed in HCC and correlated with poor prognosis in HCC patients.Functional studies showed that RCC1 overexpression promoted the malignant phenotype of HCC cells,especially the proliferation of HCC cells,whereas RCC1 knockdown had the opposite effect.Mechanistically,we identied cell division cycle-associated(CDCA)8 as a downstream target of RCC1 in HCC.RCC1 overexpression markedly increased CDCA8 levels,consequently enhancing cell proliferation and survival in HCC cells.Additionally,we discovered that RCC1 contributed to the development and progression of HCC by activating the phosphoinositide 3-kinase/protein kinase B/cyclin-dependent kinase inhibitor 1a pathway through CDCA8.CONCLUSION Our study provides profound insights into the pivotal role of RCC1 in HCC and its potential as a therapeutic target.
