PMID- 21998677 OWN - NLM STAT- MEDLINE DCOM- 20120213 LR - 20240313 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 6 IP - 10 DP - 2011 TI - MYCT1-TV, a novel MYCT1 transcript, is regulated by c-Myc and may participate in laryngeal carcinogenesis. PG - e25648 LID - 10.1371/journal.pone.0025648 [doi] LID - e25648 AB - BACKGROUND: MYCT1, a putative target of c-Myc, is a novel candidate tumor suppressor gene cloned from laryngeal squamous cell carcinoma (LSCC). Its transcriptional regulation and biological effects on LSCC have not been clarified. METHODOLOGY/PRINCIPAL FINDINGS: Using RACE assay, we cloned a 1106 bp transcript named Myc target 1 transcript variant 1 (MYCT1-TV) and confirmed its transcriptional start site was located at 140 bp upstream of the ATG start codon of MYCT1-TV. Luciferase, electrophoretic mobility shift and chromatin immunoprecipitation assays confirmed c-Myc could regulate the promoter activity of MYCT1-TV by specifically binding to the E-box elements within -886 to -655 bp region. These results were further verified by site-directed mutagenesis and RNA interference (RNAi) assays. MYCT1-TV and MYCT1 expressed lower in LSCC than those in paired adjacent normal laryngeal tissues, and overexpression of MYCT1-TV and MYCT1 could inhibit cell proliferation and invasion and promote apoptosis in LSCC cells. CONCLUSIONS/SIGNIFICANCE: Our data indicate that MYCT1-TV, a novel MYCT1 transcript, is regulated by c-Myc and down-regulation of MYCT1-TV/MYCT1 could contribute to LSCC development and function. FAU - Fu, Shuang AU - Fu S AD - Department of Medical Genetics, China Medical University, Shenyang, People's Republic of China. FAU - Guo, Yan AU - Guo Y FAU - Chen, Hong AU - Chen H FAU - Xu, Zhen-Ming AU - Xu ZM FAU - Qiu, Guang-Bin AU - Qiu GB FAU - Zhong, Ming AU - Zhong M FAU - Sun, Kai-Lai AU - Sun KL FAU - Fu, Wei-Neng AU - Fu WN LA - eng SI - GENBANK/GU997693 PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20111005 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (MYCT1 protein, human) RN - 0 (Nuclear Proteins) RN - 0 (Proto-Oncogene Proteins c-myc) RN - 0 (RNA, Messenger) SB - IM MH - Amino Acid Sequence MH - Base Sequence MH - Cell Line, Tumor MH - Cloning, Molecular MH - E-Box Elements/genetics MH - Gene Expression Regulation, Neoplastic/genetics MH - Gene Silencing MH - *Genetic Variation MH - HEK293 Cells MH - Humans MH - Laryngeal Neoplasms/genetics/*pathology MH - Molecular Sequence Data MH - Nuclear Proteins/chemistry/*genetics/metabolism MH - Promoter Regions, Genetic/genetics MH - Proto-Oncogene Proteins c-myc/deficiency/genetics/*metabolism MH - RNA, Messenger/genetics MH - Transcription Initiation Site PMC - PMC3187795 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2011/10/15 06:00 MHDA- 2012/02/14 06:00 PMCR- 2011/10/05 CRDT- 2011/10/15 06:00 PHST- 2011/08/19 00:00 [received] PHST- 2011/09/07 00:00 [accepted] PHST- 2011/10/15 06:00 [entrez] PHST- 2011/10/15 06:00 [pubmed] PHST- 2012/02/14 06:00 [medline] PHST- 2011/10/05 00:00 [pmc-release] AID - PONE-D-11-16411 [pii] AID - 10.1371/journal.pone.0025648 [doi] PST - ppublish SO - PLoS One. 2011;6(10):e25648. doi: 10.1371/journal.pone.0025648. Epub 2011 Oct 5.