Silencing of miR-1-1 and miR-133a-2 cluster expression by DNA hypermethylation in colorectal cancer

Chen, Wei Shone; Leung, Chung-Man; Pan, Hung Wei; Hu, Ling; Li, Sung Chou; Ho, Meng‐Ru; Tsai, Kuo‐Wang

doi:10.3892/or.2012.1899

Cited by 62 publications

(42 citation statements)

References 42 publications

(52 reference statements)

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“…Epigenetic silencing of miRNAs with tumor suppressor features by CpG island hypermethylation is a common hallmark of human tumors (11). Most recently, it was documented that hypermethylation of the CpG islands upstream of miR-1-133a might be involved in the downregulation of miR-133a in CRCs (12). In the present study, we showed that miR-133a was significantly downregulated in primary CRC tissues using microdissection technique.…”

Section: Discussionsupporting

confidence: 59%

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Tumor Suppressor Functions of miR-133a in Colorectal Cancer

Dong

Zhao

et al. 2013

Molecular Cancer Research

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Dysregulated microRNA (miRNA) expression was profiled through a miRNA array comparison between human colorectal cancer tumors and their adjacent normal tissues. Specifically, using laser capture microdissection, miR-133a was shown to be significantly downregulated in primary colorectal cancer specimens compared with matched adjacent normal tissue. Ectopic expression of miR-133a significantly suppressed colorectal cancer cell growth in vitro and in vivo. Cell-cycle analysis revealed that miR-133a induced a G 0 /G 1 -phase arrest, concomitant with the upregulation of the key G 1 -phase regulator p21Cip1 . We further revealed that miR-133a markedly increased p53 protein and induced p21 Cip1 transcription. Studies in silico revealed that the 3 0 UTR of the ring finger and FYVE-like domain containing E3-ubiquitin protein ligase (RFFL), which regulates p53 protein, contains an evolutionarily conserved miR-133a binding site. miR-133a repressed RFFL-3 0 UTR reporter activity and reduced RFFL protein levels, indicating that miR-133a directly bound to RFFL mRNA and inhibited RFFL translation. Moreover, miR-133a sensitized colon cancer cells to doxorubicin and oxaliplatin by enhancing apoptosis and inhibiting cell proliferation. These data add weight to the significance of miR-133a in the development of CRC.

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Section: Discussionsupporting

confidence: 59%

“…Chen and colleagues mentioned that patients with CRC with liver metastasis were associated with lower expression of miR-133a (12). Unfortunately, we did not observe such Figure 6.…”

Section: Discussioncontrasting

confidence: 56%

Tumor Suppressor Functions of miR-133a in Colorectal Cancer

Dong

Zhao

et al. 2013

Molecular Cancer Research

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“…In our previous study, miR1/133a suppressed the tumor growth and metastasis in colorectal cancer by directly targeting LASP1 3 0 UTR (10). DNA methylation inhibits the expression of miR1/133a, which could be indirectly upregulated with LASP1 expression (47). Moreover, the stimulation of TGFb significantly induces the expression of LASP1 in a time-dependent manner.…”

Section: Discussionmentioning

confidence: 99%

LIM and SH3 Protein 1 Induces TGFβ-Mediated Epithelial–Mesenchymal Transition in Human Colorectal Cancer by Regulating S100A4 Expression

Wang

Shi

Luo

et al. 2014

Clinical Cancer Research

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Purpose: The expression of LIM and SH3 protein 1 (LASP1) was upregulated in colorectal cancer cases, thereby contributing to the aggressive phenotypes of colorectal cancer cells. However, we still cannot decipher the underlying molecular mechanism associated with colorectal cancer metastasis.Experimental Design: In this study, IHC was performed to investigate the expression of proteins in human colorectal cancer tissues. Western blot analysis was used to assess the LASP1-induced signal pathway. Two-dimensional difference gel electrophoresis was performed to screen LASP1-modulated proteins and uncover the molecular mechanism of LASP1. TGFb was used to induce an epithelial-mesenchymal transition (EMT).Results: LASP1 expression was correlated with the mesenchymal marker vimentin and was inversely correlated with epithelial markers, namely, E-cadherin and b-catenin, in clinical colorectal cancer samples. The gain-and loss-of-function assay showed that LASP1 induces EMT-like phenotypes in vitro and in vivo. S100A4, identified as a LASP1-modulated protein, was upregulated by LASP1. Moreover, it is frequently coexpressed with LASP1 in colorectal cancer. S100A4 was required for EMT, and an increased cell invasiveness of colorectal cancer cell is induced by LASP1. Furthermore, the stimulation of TGFb resulted in an activated Smad pathway that increased the expression of LASP1 and S100A4. The depletion of LASP1 or S100A4 expression inhibited the TGFb signaling pathway. Moreover, it significantly weakened the proinvasive effects of TGFb on colorectal cancer cells.Conclusion: These findings elucidate the central role of LASP1 in the TGFb-mediated EMT process and suggest a potential target for the clinical intervention in patients with advanced colorectal cancer. Clin Cancer Res; 20(22); 5835-47. Ó2014 AACR.

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“…Ectopic expression of miR-1-1 in HepG2 cells caused a reduction in cell proliferation, growth and clonogenic survival by inducing apoptosis and inhibiting cell cycle progression, and mitigated the cancer-cell characteristics of these cells. Therapeutic intervention with hypomethylating agents could inhibit HCC cell growth by increasing miR-1-1 expression to inhibit expression of its two downstream oncogenes, MET (MNNG HOS transforming gene) and FoxP1 (Forkhead box protein P1) [80]. These data imply that compounds interfering with epigenetic modifications, such as DNMT and histone deacetylase inhibitors, may serve as potential novel antitumor drugs for HCC patients [81,82].…”

Section: Mirnas Add Complexity To Epigenetic Modificationmentioning

confidence: 99%

The role and clinical implications of microRNAs in hepatocellular carcinoma

Zhao

Yang

et al. 2012

Sci. China Life Sci.

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Hepatocellular carcinoma (HCC) is common and one of the most aggressive of all human cancers. Recent studies have indicated that miRNAs, a class of small noncoding RNAs that regulate gene expression post-transcriptionally, directly contribute to HCC by targeting many critical regulatory genes. Several miRNAs are involved in hepatitis B or hepatitis C virus replication and virus-induced changes, whereas others participate in multiple intracellular signaling pathways that modulate apoptosis, cell cycle checkpoints, and growth-factor-stimulated responses. When disturbed, these pathways appear to result in malignant transformation and ultimately HCC development. Recently, miRNAs circulating in the blood have acted as possible early diagnostic markers for HCC. These miRNA also could serve as indicators with respect to drug efficacy and be prognostic in HCC patients. Such biomarkers would assist stratification of HCC patients and help direct personalized therapy. Here, we summarize recent advances regarding the role of miRNAs in HCC development and progression. Our expectation is that these and ongoing studies will contribute to the understanding of the multiple roles of these small noncoding RNAs in liver tumorigenesis.

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Silencing of miR-1-1 and miR-133a-2 cluster expression by DNA hypermethylation in colorectal cancer

Cited by 62 publications

References 42 publications

Tumor Suppressor Functions of miR-133a in Colorectal Cancer

Tumor Suppressor Functions of miR-133a in Colorectal Cancer

LIM and SH3 Protein 1 Induces TGFβ-Mediated Epithelial–Mesenchymal Transition in Human Colorectal Cancer by Regulating S100A4 Expression

The role and clinical implications of microRNAs in hepatocellular carcinoma

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