MicroRNA-122, a tumor suppressor microRNA that regulates intrahepatic metastasis of hepatocellular carcinoma #

Tsai, Wei-Chih; Hsu, Paul; Lai, Tsung‐Ching; Chau, Gar‐Yang; Lin, Ching-Wen; Chen, Chun Ming; Lin, Chien-Der; Liao, Yu-Lun; Wang, Jui-Ling; Chau, Yat‐Pang; Hsu, Ming; Hsiao, Michael; Huang, Hsien-Da; Tsou, Ann-Ping

doi:10.1002/hep.22806

Cited by 540 publications

(423 citation statements)

References 42 publications

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“…A reduction in miR-122 expression has been observed both in a rat model for HCC and in human HCC samples compared with pair-matched control tissues (13). Restoration of miR-122 expression in HCC cell lines impaired in vitro migration, anchorage-independent growth, invasion, angiogenesis, and intrahepatic metastasis (14). Similar findings have been obtained by other research groups (15,16).…”

Section: Micrornas (Mirnas)supporting

confidence: 74%

“…Indeed, we observed several of these validated targets in the down-regulated set of proteins, including GYS1 and aldolase A (11). We also observed down-regulation of vimentin, which is commonly up-regulated in cancers, including HCC, and was shown to decrease significantly in HCC cells upon miR-122 expression (14,16). Vimentin is a marker for mesenchymal cells and is positively associated with invasiveness and metastatic potential (37)(38)(39).…”

Section: Resultsmentioning

confidence: 56%

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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: 74%

Section: Resultsmentioning

confidence: 56%

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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“…Although several miRNAs have been found to function as either tumor metastasis promoters or suppressors (Asangani et al, 2008;Korpal et al, 2008;Li et al, 2009;Tsai et al, 2009), the exact role that miRNAs play in cervical cancer metastasis is only beginning to be uncovered. Here, we describe our microarraybased investigation into the metastatic-related miRNA expression profile of cervical squamous cancer.…”

Section: Discussionmentioning

confidence: 99%

Characterization of the MicroRNA Expression Profile of Cervical Squamous Cell Carcinoma Metastases

Ding¹,

Wu²,

Wang³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Objectives: MicroRNAs (miRNAs) are important regulators of many physiological and pathological processes, including tumorigenesis and metastasis. In this study, we sought to determine the underlying molecular mechanisms of metastatic cervical carcinoma by performing miRNA profiling. Methods: Tissue samples were collected from ten cervical squamous cancer patients who underwent hysterectomy and pelvic lymph node (PLN) dissection in our hospital, including four PLN-positive (metastatic) cases and six PLN-negative (non-metastatic) cases. A miRNA microarray platform with 1223 probes was used to determine the miRNA expression profiles of these two tissue types and case groups. MiRNAs having at least 4-fold differential expression between PLN-positive and PLN-negative cervical cancer tissues were bioinformatically analyzed for target gene prediction. MiRNAs with tumor-associated target genes were validated by quantitative reverse transcription-polymerase chain reaction (RT-PCR). Results: Thirty-nine miRNAs were differentially expressed (>4-fold) between the PLN-positive and PLN-negative groups, of which, 22 were up-regulated and 17 were down-regulated. Sixty-nine percent of the miRNAs (27/39) had tumor-associated target genes, and the expression levels of six of those (miR-126, miR-96, miR-144, miR-657, miR-490-5p, and miR-323-3p) were confirmed by quantitative (q)RT-PCR. Conclusions: Six MiRNAs with predicted tumor-associated target genes encoding proteins that are known to be involved in cell adhesion, cytoskeletal remodeling, cell proliferation, cell migration, and apoptosis were identified. These findings suggest that a panel of miRNAs may regulate multiple and various steps of the metastasis cascade by targeting metastasis-associated genes. Since these six miRNAs are predicted to target tumor-associated genes, it is likely that they contribute to the metastatic potential of cervical cancer and may aid in prognosis or molecular therapy.

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“…Other minor processes in which miR-122 is implicated seem to include the migration-related processes. Indeed low levels of miR-122 promote overexpression of disintegrin and metalloproteinase as ADAM17 (Tsai et al, 2009) and ADAM10 (Bai et al, 2009) that promote migration. This action seems to be correlated with chronic viral infection.…”

Section: Mir-122mentioning

confidence: 99%

HepatomiRNoma: The proposal of a new network of targets for diagnosis, prognosis and therapy in hepatocellular carcinoma

Bronte

Fanale

et al. 2016

Critical Reviews in Oncology/Hematology

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MicroRNA-122, a tumor suppressor microRNA that regulates intrahepatic metastasis of hepatocellular carcinoma #

Cited by 540 publications

References 42 publications

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

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

Characterization of the MicroRNA Expression Profile of Cervical Squamous Cell Carcinoma Metastases

HepatomiRNoma: The proposal of a new network of targets for diagnosis, prognosis and therapy in hepatocellular carcinoma

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