Loss of miR-1258 contributes to carcinogenesis and progression of liver cancer through targeting CDC28 protein kinase regulatory subunit 1B
| Autor: | Minghua Hu, Xiaoshan Fang, Hongping Xia, Jin-Guo Wang, Xiaobing Chen, Huihong Lu, Mingwei Wang, Chen-Yang Ma, Xiaoming Wang |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Cell cycle checkpoint Carcinogenesis Apoptosis medicine.disease_cause Mice 0302 clinical medicine Cell Movement CDC2-CDC28 Kinases Medicine Mice Inbred BALB C Antibiotics Antineoplastic CKS1B Liver Neoplasms Flow Cytometry Gene Expression Regulation Neoplastic Cell Transformation Neoplastic Liver Oncology 030220 oncology & carcinogenesis Disease Progression miR-1258 Liver cancer Research Paper recurrence Carcinoma Hepatocellular Down-Regulation Mice Nude Disease-Free Survival liver cancer stemness 03 medical and health sciences Cell Line Tumor microRNA Biomarkers Tumor In Situ Nick-End Labeling Animals Humans Cell Proliferation business.industry Cell growth Cancer medicine.disease G1 Phase Cell Cycle Checkpoints Xenograft Model Antitumor Assays MicroRNAs 030104 developmental biology Doxorubicin Immunology Cancer research business |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | Hepatocellular carcinoma (HCC) is the leading cause of cancer related death worldwide. The number of deaths is proportional to the global incidence, which highlights the aggressive tumor biology and lack of effective therapies. Dysregulation of microRNAs has been implicated in carcinogenesis and progression of liver cancer. Here, we identified that miR-1258 was significantly downregulated in HCC and associated with poor patients' survival. Overexpression of miR-1258 significantly inhibits liver cancer cell growth, proliferation and tumorigenicity through increasing cell cycle arrest in G0/G1 phase and promotes cell apoptosis. Interestingly, stable overexpression of miR-1258 suppresses cell migration, stemness and increases sensitivity of HCC cells to chemotherapy drug like doxorubicin. The CDC28 protein kinase regulatory subunit 1B (CKS1B) was identified as a functional downstream target of miR-1258. Re-expression of CKS1B overcomes miR-1258 induced apoptosis and increases stemness of HCC cells, suggesting that loss of miR-1258 contributes to carcinogenesis and progression of liver cancer through targeting CKS1B . Therefore, loss of miR-1258 may be a potential diagnostic and prognostic biomarker and blocking miR-1258-CKS1B axis is a potential therapeutic strategy in HCC. |
| Databáze: | OpenAIRE |
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