The role of miR-506 in transformed 16HBE cells induced by anti-benzo[a]pyrene-trans-7,8-dihydrodiol-9,10-epoxide

Institute for Chemical Carcinogenesis, State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, 195 Dongfengxi Road, Guangzhou 510182, PR China.
Toxicology Letters (Impact Factor: 3.26). 09/2011; 205(3):320-6. DOI: 10.1016/j.toxlet.2011.06.022
Source: PubMed


Growing evidence indicates that the alteration of microRNA (miRNA) expression in tumors that is induced by chemical carcinogens plays an important role in tumor development and progression. However, the mechanism underlying miRNA involvement in lung carcinogenesis induced by anti-benzo[a]pyrene-trans-7,8-dihydrodiol-9,10-epoxide (anti-BPDE) remains unclear. In our study, we used the malignant transformation of human bronchial epithelial cells (16HBE-T) induced by anti-BPDE to explore the mechanisms of human lung carcinogenesis. We found that expression of miR-506 was reduced in 16HBE-T transformed malignant human bronchial epithelial cells compared with 16HBE normal human bronchial epithelial cells. Restoration of miR-506 in 16HBE-T cells led to a decrease in cell proliferation, G0/G1 phase cell cycle arrest, as well as significantly suppressed anchorage-dependent growth in vitro and tumor growth inhibition in a nude mouse xenograft model. In addition, we provided novel evidence regarding the role miR-506 potentially plays in negatively regulating the protein and mRNA expression level of N-Ras in cancer cells. Together, these findings revealed that miR-506 acts as an anti-oncogenic miRNA (anti-oncomir) in malignantly transformed cells. The identification of tumor suppressive miRNAs could provide new insight into the molecular mechanisms of chemical carcinogenesis.

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    • "It is now clear that large numbers of microRNAs (miRNAs), the most well-known ncRNAs, are highly expressed, specifically regulated, and evolutionarily conserved, arguing in favor of their functional significance in cancer progression. In the field of toxicology and chemical carcinogenesis, miRNAs have also been shown to correlate with exposure to many exogenous carcinogens (Chen, 2010; Jiang et al., 2011; Zhao et al., 2011). Such observations have provided new insight into the potential mechanisms of cancer pathology in response to carcinogens. "
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    ABSTRACT: Lung cancer is the leading cause of cancer deaths and remains an important public health problem worldwide. Long noncoding RNAs (lncRNAs) are newly identified regulators of tumorigenesis and tumor progression. However, the role of lncRNAs in lung cancer induced by environmental carcinogens remains largely unknown. In this study, an lncRNA microarray was used to compare the expression profiles of malignantly transformed 16HBE cells (16HBE-T) induced with anti-benzo[a]pyrene-trans-7,8-diol-9,10-epoxide (anti-BPDE) and normal 16HBE cells (16HBE-N). Using quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR), lncRNA AF118081 was identified as the most significantly overexpressed lncRNA in 16HBE-T cells, lung cancer cells, and patient samples. Cell proliferation, colony formation, apoptosis, migration, and invasion were assayed in 16HBE-T cells following the knockdown of lncRNA AF118081 with small interfering RNA. AF118081 knockdown inhibited cell growth and tumor invasion. An in vivo (nude mouse) model was then used to assay tumor growth, and the downregulation of AF118081 clearly suppressed tumor growth, consistent with the results of the in vitro assays. Together, these findings identify a new oncogenic lncRNA, lncRNA AF118081, in malignantly transformed 16HBE cells. This enhances our understanding of lncRNAs as important regulatory elements in chemical carcinogenesis and potential targets of lung cancer therapies.
    Toxicology Letters 07/2014; 229(3). DOI:10.1016/j.toxlet.2014.07.004 · 3.26 Impact Factor
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    • "Our sequencing results revealed that miR-509-3p and miR-508- 3p (members of the miR-506 family) are located on Xq27.3, which is a fragile site of the human X chromosome. Restoration of miR- 506 in cancers led to a decrease in cell proliferation, cell cycle arrest and significantly suppressed tumor growth [38]. Thus far, there have only been a few studies describing miR-509-3p or miR-508-3p. "
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    ABSTRACT: MicroRNAs (miRNAs) have emerged as powerful regulators of multiple processes linked to human cancer, including cell apoptosis, proliferation and migration, suggesting that the regulation of miRNA function could play a critical role in cancer progression. Recent studies have found that human serum/plasma contains stably expressed miRNAs. If they prove indicative of disease states, miRNAs measured from peripheral blood samples may be a source for routine clinical detection of cancer. Our studies showed that both miR-508-3p and miR-509-3p were down-regulated in renal cancer tissues. The level of miR-508-3p but not miR-509-3p in renal cell carcinoma (RCC) patient plasma demonstrated significant differences from that in control plasma. In addition, the overexpression of miR-508-3p and miR-509-3p suppressed the proliferation of RCC cells (786-0), induced cell apoptosis and inhibited cell migration in vitro. Our data demonstrated that miR-508-3p and miR-509-3p played an important role as tumor suppressor genes during tumor formation and that they may serve as novel diagnostic markers for RCC.
    Biochemical and Biophysical Research Communications 02/2012; 419(4):621-6. DOI:10.1016/j.bbrc.2012.02.060 · 2.30 Impact Factor
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    • "To date, the role of miR-506 in tumor cell is not clear. Zhao et al. found that expression of miR-506 was reduced in 16HBE-T transformed malignant human bronchial epithelial cells compared with 16HBE normal human bronchial epithelial cells and revealed that miR-506 acts as an anti-oncogenic miRNA (anti-oncomir) in malignantly transformed cells [17]. However, we show that miR-506 over-expression in established HCPT-resistant colon cancer cell line SW1116/HCPT confers resistance to HCPT by inhibiting PPARa expression. "
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    ABSTRACT: Chemotherapeutic drug resistance remains a major obstacle to the successful treatment of colon cancer. Here, we show that 77 differentially expressed miRNAs were identified in SW1116/HCPT versus SW1116, and over-expressed miR-506 in SW1116/HCPT cells was validated. Then it was indicated that PPARα is a common target of miR-506 by using a luciferase reporter assay. Our results also demonstrated that cytotoxic ability of HCPT requires the concomitant presence of PPARα, and that loss of PPARα expression imparts resistance to HCPTs anti-tumor effects. All together, our studies indicate that miR-506 over-expression in established HCPT-resistant colon cancer cell line confers resistance to HCPT by inhibiting PPARα expression, then providing a rationale for the development of miRNA-based strategies for reversing resistance in HCPT-resistant colon cancer cells.
    FEBS letters 11/2011; 585(22):3560-8. DOI:10.1016/j.febslet.2011.10.021 · 3.17 Impact Factor
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