Correlation of Transcription of MALAT-1, a Novel Noncoding RNA, with Deregulated Expression of Tumor Suppressor p53 in Small DNA Tumor Virus Models

DOI: 10.4236/jct.2013.43094   PDF   HTML     4,063 Downloads   6,112 Views   Citations


Although metastasis-associated lung adenocarcinoma transcript (MALAT)-1 is known to be consistently upregulated in several epithelial malignancies, little is known about its function or regulation. We therefore examined the relationship between MALAT-1 expression and candidate modulators such as DNA tumor virus oncoproteins human papillomavirus (HPV)-16 E6 and E7, BK virus T antigen (BKVTAg), mouse polyoma virus middle T antigen (MPVmTAg) and tumor suppressor genes p53 and pRb. Using suppressive subtractive hybridization (SSH) and real-time reverse transcriptase polymerase chain reaction (RT-PCR) assays, MALAT-1 was shown to be increased in viral oncongene-expressing salivary gland biopsies from humans and mice. The results also indicated that MALAT-1 transcripts and promoter activity were increased in vitro when viral oncongene-expressing plasmids were introduced into different cell types. These same viral oncogenes in addition to increasing MALAT-1 transcription have also been shown to inhibit p53 and/or pRb function. In p53 mutant or inactive cell lines MALAT-1 was also shown to be highly upregulated. We hypothesize that there is a correlation between MALAT-1 over-expression and p53 deregulation. In conclusion, we show that disruption of p53, by both polyoma and papilloma oncoproteins appear to play an important role in the up-regulation of MALAT-1. MALAT-1 might therefore represent a biomarker for p53 deregulation within malignancies.

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L. Jeffers, K. Duan, L. Ellies, W. Seaman, R. Burger-Calderon, L. Diatchenko and J. Webster-Cyriaque, "Correlation of Transcription of MALAT-1, a Novel Noncoding RNA, with Deregulated Expression of Tumor Suppressor p53 in Small DNA Tumor Virus Models," Journal of Cancer Therapy, Vol. 4 No. 3, 2013, pp. 774-786. doi: 10.4236/jct.2013.43094.

Conflicts of Interest

The authors declare no conflicts of interest.


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