Skip to main content
Erschienen in: Tumor Biology 4/2015

01.04.2015 | Research Article

Upregulated expression of miR-106a by DNA hypomethylation plays an oncogenic role in hepatocellular carcinoma

verfasst von: Renshun Yuan, Qiaoming Zhi, Hong Zhao, Ye Han, Ling Gao, Bin Wang, Zhongyang Kou, Zhaoji Guo, Songbing He, Xiaofeng Xue, Hao Hu

Erschienen in: Tumor Biology | Ausgabe 4/2015

Einloggen, um Zugang zu erhalten

Abstract

Aberrant microRNA (miRNA) expression has been widely recognized to play an extremely important role in several cancers, including hepatocellular carcinoma (HCC). According to the previous studies, abnormal miR-106a expression was closely related to various cancer occurrences. However, the miR-106a expression in HCC remains unclear. In our study, we firstly detected the miR-106a expression levels in 36 pairs of HCC tissues. The results showed that miR-106a expression in HCC tissues was apparently higher than the level in the adjacent tissues. Then, we used quantitative real-time PCR (qPCR) and BSP to analyze miR-106a expression and promoter methylation in HCC cell lines. There came to a conclusion that the methylation status of the miR-106a promoter region was inversely correlated with the expression of miR-106a. After prediction with online software, we further used dual-luciferase reporter gene assay to ensure that TP53INP1 and CDKN1A might be the direct targets of miR-106a. At last, we explored the functions of miR-106a in HCC cells in vitro. Our results manifested that high-miR-106a cell line had stronger invasiveness, faster cell cycle progression, and more resistance to apoptosis compared with the low-miR-106a cell line. Therefore, our study suggested that upregulated expression of miR-106a by its promoter hypomethylation might contribute to the progression of HCC, which might be considered as a potentially effective biomarker and therapeutic approach in the future.
Literatur
10.
Zurück zum Zitat Daniel FI, Cherubini K, Yurgel LS, de Figueiredo MA, Salum FG. The role of epigenetic transcription repression and DNA methyltransferases in cancer. Cancer. 2011;117(4):677–87. doi:10.1002/cncr.25482.CrossRefPubMed Daniel FI, Cherubini K, Yurgel LS, de Figueiredo MA, Salum FG. The role of epigenetic transcription repression and DNA methyltransferases in cancer. Cancer. 2011;117(4):677–87. doi:10.​1002/​cncr.​25482.CrossRefPubMed
14.
Zurück zum Zitat Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116(2):281–97.CrossRefPubMed Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116(2):281–97.CrossRefPubMed
18.
Zurück zum Zitat Chen X, Zhang L, Zhang T, Hao M, Zhang X, Zhang J, et al. Methylation-mediated repression of microRNA 129-2 enhances oncogenic SOX4 expression in HCC. Liver Int. 2013;33(3):476–86. doi:10.1111/liv.12097.CrossRefPubMed Chen X, Zhang L, Zhang T, Hao M, Zhang X, Zhang J, et al. Methylation-mediated repression of microRNA 129-2 enhances oncogenic SOX4 expression in HCC. Liver Int. 2013;33(3):476–86. doi:10.​1111/​liv.​12097.CrossRefPubMed
19.
Zurück zum Zitat Dohi O, Yasui K, Gen Y, Takada H, Endo M, Tsuji K, et al. Epigenetic silencing of miR-335 and its host gene MEST in hepatocellular carcinoma. Int J Oncol. 2013;42(2):411–8. doi:10.3892/ijo.2012.1724.PubMed Dohi O, Yasui K, Gen Y, Takada H, Endo M, Tsuji K, et al. Epigenetic silencing of miR-335 and its host gene MEST in hepatocellular carcinoma. Int J Oncol. 2013;42(2):411–8. doi:10.​3892/​ijo.​2012.​1724.PubMed
20.
Zurück zum Zitat Long XR, He Y, Huang C, Li J. MicroRNA-148a is silenced by hypermethylation and interacts with DNA methyltransferase 1 in hepatocellular carcinogenesis. Int J Oncol. 2014;44(6):1915–22. doi:10.3892/ijo.2014.2373.PubMed Long XR, He Y, Huang C, Li J. MicroRNA-148a is silenced by hypermethylation and interacts with DNA methyltransferase 1 in hepatocellular carcinogenesis. Int J Oncol. 2014;44(6):1915–22. doi:10.​3892/​ijo.​2014.​2373.PubMed
24.
Zurück zum Zitat Ma L, Liu J, Liu L, Duan G, Wang Q, Xu Y, et al. Overexpression of the transcription factor MEF2D in hepatocellular carcinoma sustains malignant character by suppressing G2-M transition genes. Cancer Res. 2014;74(5):1452–62. doi:10.1158/0008-5472.CAN-13-2171.CrossRefPubMed Ma L, Liu J, Liu L, Duan G, Wang Q, Xu Y, et al. Overexpression of the transcription factor MEF2D in hepatocellular carcinoma sustains malignant character by suppressing G2-M transition genes. Cancer Res. 2014;74(5):1452–62. doi:10.​1158/​0008-5472.​CAN-13-2171.CrossRefPubMed
27.
Zurück zum Zitat Harper JW, Adami GR, Wei N, Keyomarsi K, Elledge SJ. The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases. Cell. 1993;75(4):805–16.CrossRefPubMed Harper JW, Adami GR, Wei N, Keyomarsi K, Elledge SJ. The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases. Cell. 1993;75(4):805–16.CrossRefPubMed
33.
Zurück zum Zitat Wang Z, Liu M, Zhu H, Zhang W, He S, Hu C, et al. miR-106a is frequently upregulated in gastric cancer and inhibits the extrinsic apoptotic pathway by targeting FAS. Mol Carcinog. 2013;52(8):634–46. doi:10.1002/mc.21899.CrossRefPubMed Wang Z, Liu M, Zhu H, Zhang W, He S, Hu C, et al. miR-106a is frequently upregulated in gastric cancer and inhibits the extrinsic apoptotic pathway by targeting FAS. Mol Carcinog. 2013;52(8):634–46. doi:10.​1002/​mc.​21899.CrossRefPubMed
Metadaten
Titel
Upregulated expression of miR-106a by DNA hypomethylation plays an oncogenic role in hepatocellular carcinoma
verfasst von
Renshun Yuan
Qiaoming Zhi
Hong Zhao
Ye Han
Ling Gao
Bin Wang
Zhongyang Kou
Zhaoji Guo
Songbing He
Xiaofeng Xue
Hao Hu
Publikationsdatum
01.04.2015
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 4/2015
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-014-2945-2

Weitere Artikel der Ausgabe 4/2015

Tumor Biology 4/2015 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.