Background:The DNA damage repair mechanism plays a crucial role in the occurrence and development of hepatocellular carcinoma(HCC),and RAD51-associated protein 1(RAD51AP1)has received increasing attention as an import...Background:The DNA damage repair mechanism plays a crucial role in the occurrence and development of hepatocellular carcinoma(HCC),and RAD51-associated protein 1(RAD51AP1)has received increasing attention as an important protein in the homologous recombination repair pathway.However,the role of RAD51AP1 and its molecular regulatory mechanism in HCC still need further investigation.Methods:We first analysed RAD51AP1 expression,functional enrichment and prognostic value in HCC.Then,the miRWalk,miRDB,and Encyclopedia of RNA Interactomes databases were used to predict the corresponding microRNAs and long noncoding RNAs of RAD51AP1,and their expression levels and prognostic value were analysed.Results:RAD51AP1 was upregulated in the majority of cancers include HCC.The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed that RAD51AP1 was mainly involved in pathways related to the cell cycle and repair in HCC.Moreover,the expression level of RAD51AP1 was significantly correlated with T stage,pathologic stage,histologic grade and the level of alpha-fetoprotein.In addition,RAD51AP1 was an independent risk factor significantly and had a high predictive value in HCC.Based on ceRNA network,RAD51AP1 may be regulated by upstream MSC-AS1 and hsa-miR-23c to affect the HCC occurrence and development.Conclusions:High expression of RAD51AP1 plays an important biological role in the cell cycle and repair pathways,and has important diagnostic and prognostic value in HCC.Based on the regulatory mechanism of ceRNA network,we speculate that lncRNA MSC-AS1 acts on hsa-miR-23c and regulates DNA damage repair of HCC through RAD51AP1.It provides a new perspective for further study of DNA damage repair mechanism and potential related treatment of HCC.展开更多
Background： Ovarian serous adenocarcinoma can be divided into low- and high-grade tumors, which exhibit substantial differences in pathogenesis, clinicopathology, and prognosis. This study aimed to investigate the d...Background： Ovarian serous adenocarcinoma can be divided into low- and high-grade tumors, which exhibit substantial differences in pathogenesis, clinicopathology, and prognosis. This study aimed to investigate the difl＇erences in the PH domain leucine-rich repeat protein phosphatase （PHLPP）, tbrkhead llomeobox type O3a （FoxO3a）, and RAD51 protein expressions, and their associations with prognosis in patients with low- and high-grade ovarian serous adenocarcinomas. Methods： The PH LPP, FoxO3a, and RA D51 protein expressions were examined in 94 high- and 26 low-grade ovarian serous adenocarcinomas by immunohistochemistry. The differences in expression and their relationships with pathological features and prognosis were analyzed. Results： In high-grade serous adenocarcinomas, the positive rates of PHLPP and goxO3a were 24.5% and 26.6%, while in low-grade tumors, they were 23.1% and 26.9%, respectively （P 〈 0.05 vs. the control specimens; low- vs. high-grade： P 〉 0.（15）. The positive rates of RAD51 were 70.2% and 65.4% in high- and low-grade serous adenocarcinomas, respectively （P 〈 0.（15 vs. the control specimens; low- vs. high-grade： P 〉 0.05）. Meanwhile, in high-grade tumors, Stage Ⅲ/Ⅳ tumors and lymph node and omental metastases were significantly associated with lower PHLPP and FoxO3a and higher RAD51 expression. The 5-year survival rates of patients with PHLPP- and FoxO3a-positive high-grade tumors （43.5% and 36.0%） were significantly higher than in patients with PHLPP-negative tumors （5.6% and 7.2%, respectively; P 〈 0.05）. Similarly, the 5-year survival rate of RAD5 l-positive patients （3.0%） was significantly lower than in negative patients （42.9%： P〈 0.05）. In low-grade tumors, the PHLPP, FoxO3a, and RAD51 expressions were not significantly correlated with lymph node metastasis, omental metastasis, Federation of Gynecology and Obstetrics stage, or prognosis. Conclusions： Abnormal PHLPP, FoxO3a, and RAD51 protein expressions may be involved in the development of high- and low-grade ovarian serous adenocarcinomas, suggesting conlmon molecular pathways. Decreased PH LPP and FoxO3a and increased RAD51 protein expression may be important molecular markers for poor prognosis, and RAD51 may be an independent prognosis factor, of high-grade, but not low-grade, ovarian serous adenocarcinomas.展开更多
基金the financial support from Shandong Traditional Chinese Medicine Science and Technology Project(No.2020M139)the Scientific Research Project of Shandong College of Traditional Chinese Medicine(No.2021FY02)the Development Plan of Laizhou Science and Technology Project(No.2022L01).
文摘Background:The DNA damage repair mechanism plays a crucial role in the occurrence and development of hepatocellular carcinoma(HCC),and RAD51-associated protein 1(RAD51AP1)has received increasing attention as an important protein in the homologous recombination repair pathway.However,the role of RAD51AP1 and its molecular regulatory mechanism in HCC still need further investigation.Methods:We first analysed RAD51AP1 expression,functional enrichment and prognostic value in HCC.Then,the miRWalk,miRDB,and Encyclopedia of RNA Interactomes databases were used to predict the corresponding microRNAs and long noncoding RNAs of RAD51AP1,and their expression levels and prognostic value were analysed.Results:RAD51AP1 was upregulated in the majority of cancers include HCC.The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed that RAD51AP1 was mainly involved in pathways related to the cell cycle and repair in HCC.Moreover,the expression level of RAD51AP1 was significantly correlated with T stage,pathologic stage,histologic grade and the level of alpha-fetoprotein.In addition,RAD51AP1 was an independent risk factor significantly and had a high predictive value in HCC.Based on ceRNA network,RAD51AP1 may be regulated by upstream MSC-AS1 and hsa-miR-23c to affect the HCC occurrence and development.Conclusions:High expression of RAD51AP1 plays an important biological role in the cell cycle and repair pathways,and has important diagnostic and prognostic value in HCC.Based on the regulatory mechanism of ceRNA network,we speculate that lncRNA MSC-AS1 acts on hsa-miR-23c and regulates DNA damage repair of HCC through RAD51AP1.It provides a new perspective for further study of DNA damage repair mechanism and potential related treatment of HCC.
文摘Background： Ovarian serous adenocarcinoma can be divided into low- and high-grade tumors, which exhibit substantial differences in pathogenesis, clinicopathology, and prognosis. This study aimed to investigate the difl＇erences in the PH domain leucine-rich repeat protein phosphatase （PHLPP）, tbrkhead llomeobox type O3a （FoxO3a）, and RAD51 protein expressions, and their associations with prognosis in patients with low- and high-grade ovarian serous adenocarcinomas. Methods： The PH LPP, FoxO3a, and RA D51 protein expressions were examined in 94 high- and 26 low-grade ovarian serous adenocarcinomas by immunohistochemistry. The differences in expression and their relationships with pathological features and prognosis were analyzed. Results： In high-grade serous adenocarcinomas, the positive rates of PHLPP and goxO3a were 24.5% and 26.6%, while in low-grade tumors, they were 23.1% and 26.9%, respectively （P 〈 0.05 vs. the control specimens; low- vs. high-grade： P 〉 0.（15）. The positive rates of RAD51 were 70.2% and 65.4% in high- and low-grade serous adenocarcinomas, respectively （P 〈 0.（15 vs. the control specimens; low- vs. high-grade： P 〉 0.05）. Meanwhile, in high-grade tumors, Stage Ⅲ/Ⅳ tumors and lymph node and omental metastases were significantly associated with lower PHLPP and FoxO3a and higher RAD51 expression. The 5-year survival rates of patients with PHLPP- and FoxO3a-positive high-grade tumors （43.5% and 36.0%） were significantly higher than in patients with PHLPP-negative tumors （5.6% and 7.2%, respectively; P 〈 0.05）. Similarly, the 5-year survival rate of RAD5 l-positive patients （3.0%） was significantly lower than in negative patients （42.9%： P〈 0.05）. In low-grade tumors, the PHLPP, FoxO3a, and RAD51 expressions were not significantly correlated with lymph node metastasis, omental metastasis, Federation of Gynecology and Obstetrics stage, or prognosis. Conclusions： Abnormal PHLPP, FoxO3a, and RAD51 protein expressions may be involved in the development of high- and low-grade ovarian serous adenocarcinomas, suggesting conlmon molecular pathways. Decreased PH LPP and FoxO3a and increased RAD51 protein expression may be important molecular markers for poor prognosis, and RAD51 may be an independent prognosis factor, of high-grade, but not low-grade, ovarian serous adenocarcinomas.
