Author(s)

Liesl K. Jeffers, Kaiwen Duan, Lesley G. Ellies, William T. Seaman, Raquel A. Burger-Calderon, Luda B. Diatchenko, Jennifer Webster-Cyriaque

Center for Neurosensory Disorders, University of North Carolina at Chapel Hill, Chapel Hill, USA.
Department of Dental Ecology, University of North Carolina at Chapel Hill, Chapel Hill, USA.
Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, USA.
Department of Pathology, University of California-San Diego, La Jolla, USA.
Kunming University, Kunming, China.
Lineberger Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, USA.

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.

p53; MALAT-1; Transcription; BK Virus; Polyoma Virus; Papillomavirus; HPV

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.