Checkpoint kinase 1 is negatively regulated by miR-497 in hepatocellular carcinoma
- 25 January 2014
- journal article
- Published by Springer Science and Business Media LLC in Medical Oncology
- Vol. 31 (3)
- https://doi.org/10.1007/s12032-014-0844-4
Abstract
Checkpoint kinase 1 (CHEK1) is an evolutionarily conserved Ser/Thr kinase, which mediates cell-cycle arrest after DNA damage, and we previously reported that CHEK1 was overexpressed and associated with poor prognosis in hepatocellular carcinoma (HCC), indicating it was oncogenic gene. In this study, we aimed to elucidate the mechanism of CHEK1 overexpression in HCC. We first verified the upregulated CHEK1 by qRT-PCR and western blot in 30 HCC samples compared with corresponding non-tumor liver tissues. In silico analysis showed that CHEK1 was a candidate target of miR-497, which was previously found to be downregulated in HCC by us. To test whether miR-497 could bind to 3′untranslated region (3′UTR) of CHEK1, luciferase reporter assay was conducted. The result revealed that miR-497 could bind to the 3′untranslated region (3′UTR) of CHEK1 mRNA. Western blot showed that ectopic expression of miR-497 suppressed the CHEK1 expression and inhibition of miR-497 led to significant upregulation of CHEK1. Finally, miR-497 expression was measured in the same 30 HCC samples, and the correlation between miR-497 and CHEK1 was analyzed. The results indicated that miR-497 was downregulated in HCC and had a significant negative correlation with CHEK1. Taken together, these results demonstrated that CHEK1 was negatively regulated by miR-497, and the overexpressed CHEK1 was resulted from the downregulated miR-497 in HCC, which provided a potential molecular target for HCC therapy.Keywords
This publication has 27 references indexed in Scilit:
- Clinical Significance and Prognostic Value of microRNA Expression Signatures in Hepatocellular CarcinomaClinical Cancer Research, 2013
- MicroRNA-497 targets insulin-like growth factor 1 receptor and has a tumour suppressive role in human colorectal cancerOncogene, 2012
- Stat3-mediated activation of microRNA-23a suppresses gluconeogenesis in hepatocellular carcinoma by down-regulating Glucose-6-phosphatase and peroxisome proliferator-activated receptor gamma, coactivator 1 alphaJournal of Hepatology, 2012
- New Insights into Checkpoint Kinase 1 in the DNA Damage Response Signaling NetworkClinical Cancer Research, 2010
- miR-200a-mediated downregulation of ZEB2 and CTNNB1 differentially inhibits nasopharyngeal carcinoma cell growth, migration and invasionBiochemical and Biophysical Research Communications, 2010
- Changes in microRNA expression levels correlate with clinicopathological features and prognoses in endometrial serous adenocarcinomasCancer Science, 2009
- Identification of Novel Kinase Targets for the Treatment of Estrogen Receptor–Negative Breast CancerClinical Cancer Research, 2009
- Differential expression of microRNA species in human gastric cancer versus non‐tumorous tissuesJournal of Gastroenterology and Hepatology, 2009
- The E2F-Regulated Gene Chk1 Is Highly Expressed in Triple-Negative Estrogen Receptor−/Progesterone Receptor−/HER-2− Breast CarcinomasCancer Research, 2007
- Chaperoning Checkpoint Kinase 1 (Chk1), an Hsp90 Client, with Purified ChaperonesOnline Journal of Public Health Informatics, 2006