• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10439-10444
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• 2015

Many chemotherapeutic agents have been successfully used to treat hepatocellular carcinoma (HCC); however, the development of chemoresistance in liver cancer cells usually results in a relapse and worsening of prognosis. It has been demonstrated that DNA methylation and histone modification play crucial roles in chemotherapy resistance. Currently, extensive research has shown that there is another potential mechanism of gene expression control, which is mediated through the function of short noncoding RNAs, especially for microRNAs (miRNAs), but little is known about their roles in cancer cell drug resistance. In present study, by taking advantage of miRNA effects on the resistance of human hepatocellular carcinoma cells line to cisplatin, it has been demonstrated that miR-340 were significantly downregulated whereas Nrf2 was upregulated in HepG2/CDDP (cisplatin) cells, compared with parental HepG2 cells. Bioinformatics analysis and luciferase assays of Nrf2-3'-untranslated region-based reporter constructor indicated that Nrf2 was the direct target gene of miR-340, miR-340 mimics suppressing Nrf2-dependent antioxidant pathway and enhancing the sensitivity of HepG2/CDDP cells to cisplatin. Interestingly, transfection with miR-340 mimics combined with miR-340 inhibitors reactivated the Nrf2 related pathway and restored the resistance of HepG2/CDDP cells to CDDP. Collectively, the results first suggested that lower expression of miR-340 is involved in the development of CDDP resistance in hepatocellular carcinoma cell line, at least partly due to regulating Nrf2-dependent antioxidant pathway.

• Molecules and Cells
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• v.40 no.9
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• pp.667-676
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• 2017

Abnormal differentiation of muscle is closely associated with aging (sarcopenia) and diseases such as cancer and type II diabetes. Thus, understanding the mechanisms that regulate muscle differentiation will be useful in the treatment and prevention of these conditions. Protein lysine acetylation and methylation are major post-translational modification mechanisms that regulate key cellular processes. In this study, to elucidate the relationship between myogenic differentiation and protein lysine acetylation/methylation, we performed a PCR array of enzymes related to protein lysine acetylation/methylation during C2C12 myoblast differentiation. Our results indicated that the expression pattern of HDAC11 was substantially increased during myoblast differentiation. Furthermore, ectopic expression of HDAC11 completely inhibited myoblast differentiation, concomitant with reduced expression of key myogenic transcription factors. However, the catalytically inactive mutant of HDAC11 (H142/143A) did not impede myoblast differentiation. In addition, wild-type HDAC11, but not the inactive HDAC11 mutant, suppressed MyoD-induced promoter activities of MEF2C and MYOG (Myogenin), and reduced histone acetylation near the E-boxes, the MyoD binding site, of the MEF2C and MYOG promoters. Collectively, our results indicate that HDAC11 would suppress myoblast differentiation via regulation of MyoD-dependent transcription. These findings suggest that HDAC11 is a novel critical target for controlling myoblast differentiation.

• Journal of Genetic Medicine
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• v.6 no.1
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• pp.1-7
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• 2009

Epigenetic changes represented by promoter CpG island hypermethylation and histone modification are an important carcinogenetic mechanism, which is found in virtually all histologic types of human cancer. About 60-70% of human genes harbor CpG islands in their promoters and 5' exonal sequences, and some of them undergo aberrant promoter CpG island hypermethylation and subsequent downregulation of gene expression. The loss of expression in tumor suppressor or tumor-related genes results in acceleration of tumorigenic processes. In addition to regional CpG island hypermethylation, diffuse genomic hypomethylation represents an important aspect of DNA methylation changes occurring in human cancer cells and contributes to chromosomal instability. These apparently contrasting methylation changes occur not only in human cancer cells, but also in premalignant cells. CpG island hypermethylation has gained attention for not only the tumorigenic mechanistic process, but also its potential utilization as a tumor biomarker. DNA methylation markers are actively investigated for their potential uses as tumor biomarkers for diagnosis of tumors in body fluids, prognostication of cancer patients, or prediction of chemotherapeutic drug response. In this review, these aspects will be discussed in detail.