ABSTRACT
Both overall survival (OS) and disease-specific survival (DSS) are significant when determining a patient's prognosis for breast cancer (BC). The effect of DSS-related microRNAs on BC susrvival, however, is not well understood. Here, we spotted differentially expressed miRNAs (DEMs) in the TCGA database of BC DSS, identified eight DSS-related miRNAs, and constructed a risk model. AUC values at 1, 3, and 5 years were 0.852, 0.861, and 0.868, respectively, indicating a risk model's excellent prognostic prediction ability. Then, we validated miRNA roles in BC OS and finally defined miR-551b as an independently prognostic miRNA in BC. According to function analysis, miR-551b is strongly linked with the emergence and spread of cancer, including protein ubiquitination, intracellular protein transport, metabolic pathways, and cancer pathways. Moreover, we confirmed the low expression of miR-551b in BC tissue and cells. After miR-551b inhibition or overexpression, cell function was either dramatically increased or diminished, respectively, indicating that miR-551b could regulate BC proliferation, invasion, and migration. In conclusion, we thoroughly clarified BC-related miRNAs on DSS and OS and verified miR-551b as a crucial regulator in the development and prognosis of cancer. These results can offer fresh ideas for BC therapy.
ABSTRACT
MicroRNAs (miRNAs) are powerful regulators in the tumorigenesis of cholangiocarcinoma (CCA). Previous studies report that miR-551b-3p acts as an oncogenic factor in ovarian cancer, but plays a tumour suppressive role in gastric cancer. However, the expression pattern and potential function of miR-551b-3p were still unclear in CCA. Therefore, this study aimed to explore the expression of miR-551b-3p and its role as well as molecular mechanism in CCA. Analysis of TCGA dataset suggested that miR-551b-3p was under-expressed in CCA tissues compared to normal bile duct tissues. Furthermore, our data confirmed the decreased levels of miR-551b-3p in CCA samples and cell lines. Interestingly, TCGA data suggested that low miR-551b-3p level indicated reduced overall survival of CCA patients. Gain- and loss-of-function experiments found that miR-551b-3p inhibited the proliferation, G1-S phase transition and induced apoptosis of CCA cells. In vivo experiments revealed that ectopic expression of miR-551b-3p inhibited tumour growth of CCA in mice. Further investigation demonstrated that miR-551b-3p directly bond to the 3'-UTR of Cyclin D1 (CCND1) mRNA and negatively regulated the abundance of CCND1 in CCA cells. An inverse correlation between miR-551b-3p expression and the level of CCND1 mRNA was detected in CCA tissues from TCGA dataset. Notably, CCND1 knockdown showed similar effects to miR-551b-3p overexpression in HuCCT-1 cells. CCND1 restoration rescued miR-551b-3p-induced inhibition of proliferation, G1 phase arrest and apoptosis in HuCCT-1 cells. In summary, miR-551b-3p inhibits the expression of CCND1 to suppress CCA cell proliferation and induce apoptosis, which may provide a theoretical basis for improving CCA treatment.
Subject(s)
Apoptosis/genetics , Bile Duct Neoplasms/metabolism , Cell Proliferation/genetics , Cholangiocarcinoma/metabolism , Cyclin D1/metabolism , G1 Phase Cell Cycle Checkpoints/genetics , MicroRNAs/metabolism , 3' Untranslated Regions , Animals , Bile Duct Neoplasms/genetics , Cell Line, Tumor , Cholangiocarcinoma/genetics , Cyclin D1/genetics , Databases, Genetic , Gene Expression Regulation, Neoplastic/genetics , Humans , Mice , Mice, Inbred BALB C , Mice, Nude , MicroRNAs/genetics , Transplantation, HeterologousABSTRACT
AIM:To investigate the expression of long non-coding RNA PVT1 in ovarian cancer and the role of PVT1 in migration and invasion abilities of ovarian cancer cells.METHODS: The expression of PVT1 in ovarian cancer tissue,normal ovarian tissue and different ovarian cancer cell lines was detected by qPCR.Transwell assay was used to de-tect the invasion ability of ovarian cancer cells after PVT1 silencing.The migration ability of the ovarian cancer cells after PVT1 silencing was detected by scratch test.The interaction between PVT1 and microRNA(miR)-551 was analyzed by dual-luciferase reporter assay.The effect of miR-551-inhibitor on the invasion and migration abilities of ovarian cancer cells after PVT1 silencing was detected by Transwell assay and scratch test.The expression of Wnt signaling pathway-related pro-teins was determined by Western blot after PVT1 silencing.The effects of PVT1 silencing on tumor weight and volume of ovarian cancer were examined by subcutaneous tumor transplantation in nude mice.RESULTS:The expression of PVT1 in ovarian cancer tissue was significantly higher than that in normal ovarian tissue(P<0.05).The expression level of PVT1 in ovarian cancer cell line ES-2 was the highest.PVT1 silencing inhibited the invasion and migration abilities of the ovarian cancer cells.After PVT1 silencing,miR-551-inhibitor promoted the invasion and migration abilities of the ovarian cancer cells.The expression of Wnt signaling pathway-related proteins was decreased after PVT1 silencing(P<0.05).Compared with negative control group,the tumor volume and weight in PVT1-siRNA group were significantly decreased(P<0.05). CONCLUSION:PVT1 plays an important role in the development of ovarian cancer.PVT1 regulates the invasion and mi-gration abilities of ovarian cancer cells through Wnt signaling pathway.