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Expression and Function of C1orf132 Long-Noncoding Rna, in Breast Cancer Cell Lines and Tissues
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DOR
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20.1001.2.9920068682.1399.1.1.49.3
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نویسنده
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Malekzadeh Shafaroudi Afsaneh ,Sharifi Zarchi Ali ,Nafisi Nahid ,Oliviero Salvatore ,M. Matin Maryam
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منبع
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ژنتيك ايران - 1399 - دوره : 16 - شانزدهمین کنگره و چهارمین کنگره بین المللی ژنتیک ایران - کد همایش: 99200-68682
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چکیده
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Background and aim: mir-29b2 and mir-29c play a suppressive role in breast cancer progression. mir29b2chg/c1orf132 is the host gene for generating both micrornas. however, there existed longer transcripts of the gene, with unknown function. methods: here, we have employed bioinformatics and experimental approaches to decipher expression of two different c1orf132 transcripts in different types of breast cancer cell lines and tissues. results: our data demonstrated a significant downregulation of c1orf132 in triple-negative type of breast cancer. we also find out that a mouse homolog of c1orf132 is located at a similar genomic location as its human counterpart, between cd46 and cd34 genes. conclusion: the latter finding suggests new potential functions for the lncrna, other than being a simple mir-29 host gene. we predicted a putative promoter for the longer transcripts of c1orf132. the functionality of the distal promoter confirmed by transfecting mcf7 cells with a c1orf132 promoter-gfp construct. knocking-down the promoter by means of the crispr/cas9 approach revealed no alteration in the expression level of neighboring genes, cd46 and cd34. however, the expression level of mir-29c was reduced by half, suggesting an enhancer effect of the distal promoter on mir-29cf generation. furthermore, the promoter knock-down revealed a g2/m cell cycle arrest and an elevation of migration ability in mcf12a edited cells. moreover, the expression of cell mobility genes e.g. cdh2, fgf2, fgfr1 and the stem cell and emt -associated transcription factor zeb1 was significantly overexpressed in edited cells. altogether, we are reporting here the existence of an additional/distal promoter with an enhancer effect on mir-29 generation and an inhibitory effect on cell proliferation and cell migration.
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کلیدواژه
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Long-Noncoding Rna ,Triple-Negative Breast Cancer ,Crispr/Cas9 ,Emt
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آدرس
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Ferdowsi University Of Mashhad, Iran, Sharif University Of Technology, Iran, Iran University Of Medical Sciences, Iran, University Of Turin, Italy, Ferdowsi University Of Mashhad, Iran
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Authors
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