The role of miR-506 in transformed 16HBE cells induced by anti-benzo[a]pyrene-trans-7,8-dihydrodiol-9,10-epoxide.
ABSTRACT 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.
- SourceAvailable from: sciencedirect.com[Show abstract] [Hide abstract]
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; · 3.36 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Although significant advances have recently been made in the diagnosis and treatment of cervical carcinoma, the long-term survival rate for advanced cervical cancer remains low. Therefore, an urgent need exists to both uncover the molecular mechanisms and identify potential therapeutic targets for the treatment of cervical cancer. MicroRNAs (miRNAs) have important roles in cancer progression and could be used as either potential therapeutic agents or targets. miR-506 is a component of an X chromosome-linked miRNA cluster. The biological functions of miR-506 have not been well established. In this study, we found that miR-506 expression was downregulated in approximately 80% of the cervical cancer samples examined and inversely correlated with the expression of Ki-67, a marker of cell proliferation. Gain-of-function and loss-of-function studies in human cervical cancer, Caski and SiHa cells, demonstrated that miR-506 acts as a tumor suppressor by inhibiting cervical cancer growth in vitro and in vivo. Further studies showed that miR-506 induced cell cycle arrest at the G1/S transition, and enhanced apoptosis and chemosensitivity of cervical cancer cell. We subsequently identified Gli3, a hedgehog pathway transcription factor, as a direct target of miR-506 in cervical cancer. Furthermore, Gli3 silencing recapitulated the effects of miR-506, and reintroduction of Gli3 abrogated miR-506-induced cell growth arrest and apoptosis. Taken together, we conclude that miR-506 exerts its anti-proliferative function by directly targeting Gli3. This newly identified miR-506/Gli3 axis provides further insight into the pathogenesis of cervical cancer and indicates a potential novel therapeutic agent for the treatment of cervical cancer.Oncogene advance online publication, 10 March 2014; doi:10.1038/onc.2014.9.Oncogene 03/2014; · 8.56 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Porcine reproductive and respiratory syndrome (PRRS) is one of the most economically important diseases of swine, which is caused by PRRS virus (PRRSV). CD151, one of PRRSV entry mediators, determines the cell susceptibility for PRRSV. Emerging evidence indicates that the host microRNAs (miRNAs) play key roles in modulating virus infection and viral pathogenesis. In the present study, targeting porcine CD151 miRNAs were identified, and their function during PRRSV infection in MARC-145 cells was further verified. We found that miR-506 could directly target porcine CD151 3'-UTR mRNA by luciferase reporter assay. Overexpression of miR-506 significantly decreased CD151 expression at both mRNA and protein levels. Furthermore, overexpression of miR-506 reduced cellular PRRSV replication and virus release in MARC-145 cells. Our results suggested that miR-506 could inhibit PRRSV replication by directly targeting PRRSV receptor of CD151 in MARC-145 cells. However, the molecular mechanisms of miR-506 and its function in vivo need further investigation.Molecular and Cellular Biochemistry 05/2014; · 2.39 Impact Factor