MicroRNA-21 Regulates Expression of the PTEN Tumor Suppressor Gene in Human Hepatocellular Cancer

Meng, Fanyin; Henson, Roger; Wehbe–Janek, Hania; Ghoshal, Kalpana; Jacob, Samson T.; Patel, Tushar

doi:10.1053/j.gastro.2007.05.022

Cited by 2,434 publications

(2,149 citation statements)

References 32 publications

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“…Recent evidences indicate that miRNAs could contribute to oncogenesis, participating as tumor suppressors or as oncogenes (Kent and Mendell, 2006). In fact, miR-21 was shown to directly target the tumor suppressor PTEN (encoding a phosphatase that can inhibit growth and/or survival pathways) in cholangiocarcinoma cells (Meng et al, 2007). Moreover, the miR-221/222 cluster, upregulated in thyroid and prostate cancer, was shown to target the p27 kip1 protein, a critical negative regulator of the cell cycle (Galardi et al, 2007;Visone et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Regulation of microRNA expression by HMGA1 proteins

et al. 2009

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The High Mobility Group proteins HMGA1 are nuclear architectural factors that play a critical role in a wide range of biological processes. Since recent studies have identified the microRNAs (miRNAs) as important regulators of gene expression, modulating critical cellular functions such as proliferation, apoptosis and differentiation, the aim of our work was to identify the miRNAs that are physiologically regulated by HMGA1 proteins. To this purpose, we have analysed the miRNA expression profile of mouse embryonic fibroblasts (MEFs) carrying two, one or no Hmga1 functional alleles using a microarray (miRNA microarray). By this approach, we found a miRNA expression profile that differentiates Hmga1-null MEFs from the wild-type ones. In particular, a significant decrease in miR-196a-2, miR-101b, miR-331 and miR-29a was detected in homozygous Hmga1-knockout MEFs in comparison with wild-type cells. Consistently, these miRNAs are downregulated in most of the analysed tissues of Hmga1-null mice in comparison with the wild-type mice. ChIP assay shows that HMGA1 is able to bind regions upstream of these miRNAs. Moreover, we identified the HMGA2 gene product as a putative target of miR-196a-2, suggesting that HMGA1 proteins are able to downregulate the expression of the other member of the HMGA family through the regulation of the miR-196a-2 expression. Finally, ATXN1 and STC1 gene products have been identified as targets of miR-101b. Therefore, it is reasonable to hypothesize that HMGA1 proteins are involved in several functions by regulating miRNA expression.

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Section: Introductionmentioning

confidence: 99%

Regulation of microRNA expression by HMGA1 proteins

et al. 2009

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“…They encode for tumor suppressor proteins, including the phosphatase PTEN in human hepatocellular carcinoma (Meng et al, 2007), the cytoskeleton component tropomyosin-1 (TPM1) in breast cancer cells , the translational regulator PDCD4 in colorectal carcinoma and breast cancer cells (Asangani et al, 2008;Frankel et al, 2008;Zhu et al, 2008), maspin in breast cancer cells (Zhu et al, 2008). Moreover, in the recent report on the PMA-mediated induction of miR-21 in PML cells, the transcript encoding the nuclear factor NFI-B was characterized as a novel miR-21 target .…”

Section: Discussionmentioning

confidence: 99%

“…Although inactivating the two upstream sites minimally affected the tamoxifen-mediated RAS induction of the miR-21 promoter, the downstream AP-1 site exhibited the strongest effect, comparably with the triple mutation (Figure 5b). A RAS-dependent AP-1-miR-21-PDCD4 regulatory loop F Talotta et al PDCD4 and PTEN are downregulated by an AP-1-and miR-21-dependent mechanism in response to RAS Several miR-21 target transcripts, including the tumor suppressors PDCD4 (Frankel et al, 2008;Asangani et al, 2008;Lu et al, 2008), PTEN (Meng et al, 2007) and TPM1 have been experimentally validated.…”

Section: Identification Of the Ras-responsive Ap-1 Sites Of The Mir-2mentioning

confidence: 99%

An autoregulatory loop mediated by miR-21 and PDCD4 controls the AP-1 activity in RAS transformation

et al. 2008

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The transcription factor AP-1 plays key roles in tumorigenesis, by regulating a variety of protein-coding genes, implicated in multiple hallmarks of cancer. Among non-coding genes, no AP-1 target has been described yet in tumorigenesis. MicroRNAs (miRNAs) are negative post-transcriptional regulators of protein-coding genes. miRNA expression signatures are highly relevant in cancer and several tumor-associated miRNAs (oncomirs) play critical roles in oncogenesis. Here, we show that the miRNA miR-21, which represents the most frequently upregulated oncomir in solid tumors, is induced by AP-1 in response to RAS. By analyzing validated miR-21 targets, we have found that the tumor suppressors PTEN and PDCD4 are downregulated by RAS in an AP-1-and miR-21-dependent fashion. We further show that, given the role of PDCD4 as negative regulator of AP-1, the miR-21-mediated downregulation of PDCD4 is essential for the maximal induction of AP-1 activity in response to RAS. Our data reveal a novel mechanism of positive autoregulation of the AP-1 complex in RAS transformation and disclose the function of oncomirs as critical targets and regulators of AP-1 in tumorigenesis.

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“…[10][11][12][13] Altered expression of miRNAs in primary human cancers has been used for tumor diagnosis, classification, staging and prognosis. 14 Furthermore, the involvement of miRNAs in the response of tumor cells to chemotherapeutic agents has also been confirmed, [15][16][17] which suggests that miRNAs could have a broad effect on the response of cancer cells to chemotherapy.…”

Section: Introductionmentioning

confidence: 90%

MicroRNA-141 confers resistance to cisplatin-induced apoptosis by targeting YAP1 in human esophageal squamous cell carcinoma

et al. 2011

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MicroRNAs (miRNAs) are endogenous non-coding RNAs that function as negative regulators of gene expression. Alterations in miRNA expression have been shown to affect tumor growth and response to chemotherapy. In this study, we explored the possible role of miRNAs in cisplatin resistance in esophageal squamous cell carcinoma (ESCC). First we assessed the sensitivity of nine human ESCC cell lines (KYSE series) to cisplatin using an in vitro cell viability assay, and then we compared the miRNA profiles of the cisplatin-sensitive and -resistant cell lines by miRNA microarray analysis. The two groups showed markedly different miRNA expression profiles, and 10 miRNAs were found to be regulated differentially between the two groups. When miR-141, which was the most highly expressed miRNA in the cisplatin-resistant cell lines, was expressed ectopically in the cisplatin-sensitive cell lines, cell viability after cisplatin treatment was increased significantly. Furthermore, we found that miR-141 directly targeted the 3¢-untranslated region of YAP1, which is known to have a crucial role in apoptosis induced by DNA-damaging agents, and thus downregulated YAP1 expression. Our study highlights an important regulatory role for miR-141 in the development of cisplatin resistance in ESCC.

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MicroRNA-21 Regulates Expression of the PTEN Tumor Suppressor Gene in Human Hepatocellular Cancer

Cited by 2,434 publications

References 32 publications

Regulation of microRNA expression by HMGA1 proteins

Regulation of microRNA expression by HMGA1 proteins

An autoregulatory loop mediated by miR-21 and PDCD4 controls the AP-1 activity in RAS transformation

MicroRNA-141 confers resistance to cisplatin-induced apoptosis by targeting YAP1 in human esophageal squamous cell carcinoma

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