miR-122 affects the viability and apoptosis of hepatocellular carcinoma cells

Wu, Xia; Wu, Shuaiqin; Tong, Lei; Luan, Tian; Lin, Lexun; Lü, Shu-Lan; Zhao, Wenran; Ma, Qianqian; Liu, Huimin; Zhong, Zhaohua

doi:10.3109/00365520903215305

Cited by 58 publications

(53 citation statements)

References 20 publications

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“…Similar findings have been obtained by other research groups (15,16). In addition, miR-122 has been shown to influence apoptosis; transfections of the hepatoma cell line Huh-7 with a miR-122 mimic produced an up-regulation in apoptosis levels as indicated by both flow cytometry and TUNEL assay (17).…”

Section: Micrornas (Mirnas)supporting

confidence: 76%

Two-tiered Approach Identifies a Network of Cancer and Liver Disease-related Genes Regulated by miR-122

Boutz

Collins

Suresh

et al. 2011

Journal of Biological Chemistry

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MicroRNAs function as important regulators of gene expression and are commonly linked to development, differentiation, and diseases such as cancer. To better understand their roles in various biological processes, identification of genes targeted by microRNAs is necessary. Although prediction tools have significantly helped with this task, experimental approaches are ultimately required for extensive target search and validation. We employed two independent yet complementary high throughput approaches to map a large set of mRNAs regulated by miR-122, a liver-specific microRNA implicated in regulation of fatty acid and cholesterol metabolism, hepatitis C infection, and hepatocellular carcinoma. The combination of luciferase reporterbased screening and shotgun proteomics resulted in the identification of 260 proteins significantly down-regulated in response to miR-122 in at least one method, 113 of which contain predicted miR-122 target sites. These proteins are enriched for functions associated with the cell cycle, differentiation, proliferation, and apoptosis. Among these miR-122-sensitive proteins, we identified a large group with strong connections to liver metabolism, diseases, and hepatocellular carcinoma. Additional analyses, including examination of consensus binding motifs for both miR-122 and target sequences, provide further insight into miR-122 function. MicroRNAs (miRNAs)4 are small (20 -24 nt) endogenously expressed noncoding RNAs that regulate the translational efficiency and/or degradation of specific mRNAs. First discovered in Caenorhabditis elegans (1), miRNAs have since been identified in a diverse set of eukaryotic organisms as well as viruses, with over 700 miRNAs currently identified in humans (2). miRNAs function via the RNAi pathway, guiding the RNAinduced silencing complex to mRNAs by Watson-Crick base pairing between the miRNA and target mRNA (reviewed in Ref.3). The resulting interaction leads to translational repression of the mRNA, although how this repression is achieved remains unclear. Several mechanisms have been proposed (reviewed in Ref. 4), and many questions remain; however, it is clear that sequence complementarity lies at the heart of miRNA function. In animals, sequence complementarity between an miRNA and its target mRNA is rarely perfect. The vast majority of binding sites contain mismatches between strands, and these mismatches have been shown to play an important functional role in target repression (5, 6). Imperfect complementarity allows for a greater variability of target sequences, thus increasing the number of potential binding sites for a given miRNA, with estimates of 300 -400 targets on average per miRNA (7). Although many potential miRNA targets can be identified through predictions, no computational approach is all-inclusive, and even highly conservative predictions must be validated by experimental means to verify functional relevance.Certain miRNAs have caught the attention of scientists due to their strong connections to diseases and cancer. Such is the

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Section: Micrornas (Mirnas)supporting

confidence: 76%

Two-tiered Approach Identifies a Network of Cancer and Liver Disease-related Genes Regulated by miR-122

Boutz

Collins

Suresh

et al. 2011

Journal of Biological Chemistry

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“…No significant alterations were found in the proliferation of Huh7, HepG2, and QSG-7701 cells treated with 5-aza-dc in the present study; however, miRNA-122 expression levels were significantly elevated, which is less consistent with previous reports (Gramantieri et al, 2007;Wu et al, 2009). The reasons for this difference may be associated with the low levels of miRNA-122 expression in the 3 hepatic cell lines themselves; the levels of miRNA-122 elevation were limited after demethylation treatment and insufficient to induce cell proliferation-related changes.…”

Section: Discussioncontrasting

confidence: 56%

Methylation regulation of liver-specific microRNA-122 expression and its effects on the proliferation and apoptosis of hepatocellular carcinoma cells

Xing

Xu²,

Yu³

et al. 2013

Genet. Mol. Res.

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ABSTRACT. The regulation mechanism and significance of microRNA-122 (miRNA-122) expression are unclear. The aim of this study was to investigate the effects of DNA methylation on liverspecific miRNA-122 expression, cell proliferation, and apoptosis in hepatocellular carcinoma. Methylation of the miRNA-122 promoter region was detected through methylation sequencing. The level of miRNA-122 expression was measured using real-time quantitative polymerase chain reaction. The proliferation and apoptosis of hepatocellular cell lines were detected using flow cytometry and Cell Counting Kit-8 assays. Compared with those in human primary hepatocytes, methylation levels of the miRNA-122 promoter in the Huh7, HepG2, and QSG-7701 cell lines were significantly increased (P = 0.000). Similarly, levels of miRNA-122 expression in these cell lines significantly decreased (P = 0.007). After treatment with 5-aza-2-deoxycytidine, the Huh7 and HepG2 cell lines displayed a significantly lower degree of methylation (P = 0.038 and 0.025), and the levels Methylation of miRNA-122 in hepatocellular carcinoma cells of miRNA-122 expression were significantly higher (P = 0.008 and 0.003) than those in the blank group. Compared with the blank group, apoptosis of Huh7 and HepG2 cells was significantly increased (P = 0.001 and 0.027). We concluded that the expression of miRNA-122 is regulated by DNA methylation and correlated with apoptosis of liver cancer cells. Methylation regulation of miRNA-122 expression might be involved in the development of hepatocellular carcinoma.

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“…miR-122 is a hepatic tumor suppressor miR-122 levels are reduced in experimental models and human samples of HCC, and loss of miR-122 is associated with tumor invasiveness and cancer progression (13)(14)(15). Therefore, it has been speculated that this miR acts as a tumor suppressor.…”

Section: Other Functions Of Mir-122mentioning

confidence: 99%