Abstract
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.
Highlights
Metastasis-associated lung adenocarcinoma transcript-1 (MALAT-1) is a novel large, noncoding RNA
We examined the relationship between metastasis-associated lung adenocarcinoma transcript (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
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
Summary
Metastasis-associated lung adenocarcinoma transcript-1 (MALAT-1) is a novel large, noncoding RNA. Up-regulation of MALAT-1 has been shown to predict unfavorable outcomes of drug therapy in patients with osteosarcoma [4] and its 3’ end is an important biological motif in the invasion and metastasis of colorectal cancer cells [9]. These malignancies all have been associated with malfunction of p53 [10,11] a nuclear transcription factor that plays a role in cellular stress, including its accumulation during DNA damage and oncogene activation. P53 has been established as a key tumor suppressor, apoptosis inducer, and prognostic marker in cancer, with about 50% of human tumors encoding for a mutated p53 gene [12]
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