Contribution of LATS1 and LATS2 promoter methylation in OSCC development
The aberrant DNA methylation of the tumor suppressor genes involved in DNA Damage Response (DDR) signaling and cell cycle regulation may lead to the tumorigenesis. Our purpose here is to analyze the promoter methylation and mRNA expression levels of LATS1 and LATS2 (LATS1/2) genes in OSCC. Promoter methylation status of LATS1/2 genes was evaluated in 70 OSCC paraffin-embedded tissues and 70 normal oral samples, using Methylation Specific PCR (MSP). LATS1/2 mRNA expression profiles were also investigated in 14 OSCC patients and 14 normal samples, using real-time PCR. In both candidate genes, promoter methylation assessment revealed significant relationship between cases and controls (OR = 2.24, 95 % CI = 1.40–3.54, P = 0.001; LATS1 and OR = 15.5, 95%CI = 3.64–64.76, P < 0.001; LATS2). As well as, the evaluation of mRNA expression levels showed decreased expression in OSCC tissues in compare to control tissues. (Mean ± SD 1.74 ± 0.14 in OSCC versus 2.10 ± 0.24 in controls, P < 0.001; LATS1 and Mean ± SD 1.36 ± 0.077 in OSCC versus 1.96 ± 0.096 in controls, P < 0.001; LATS2). To the best our knowledge, this is the first report regarding the down-regulation of LATS1/2 through promoter methylation in OSCC. It is suggested to explore the down-stream transcription factors of both genes for finding the molecular mechanism of this deregulation in OSCC.
KeywordsOSCC LATS1 LATS2 DNA methylation Gene expression
We kindly acknowledge to our colleagues in department of Ophthalmology, Al-Zahra Eye Hospital, Zahedan University of Medical Sciences, and in the department of Biology, University of Sistan and Baluchestan, for their technical supports.
Compliance with ethical standards
Conflicts of interest
The authors declare no conflict of interest.
Research involving human participants
All procedures performed in studies involving human participants was in accordance with the ethical standards.
Informed consent was obtained from all individual participants included in the study.
- Takahashi Y, Miyoshi Y, Takahata C, Irahara N, Taguchi T, Tamaki Y, Noguchi S (2005) Down-regulation of LATS1 and LATS2 mRNA expression by promoter hypermethylation and its association with biologically aggressive phenotype in human breast cancers. Clin Cancer Res 11:1380–1385CrossRefPubMedGoogle Scholar
- Wierzbicki PM, Adrych K, Kartanowicz D, Stanislawowski M, Kowalczyk A, Godlewski J, Skwierz-Bogdanska I, Celinski K, Gach T, Kulig J et al (2013) Underexpression of LATS1 TSG in colorectal cancer is associated with promoter hypermethylation. World J Gastroenterol 19:4363–4373CrossRefPubMedPubMedCentralGoogle Scholar
- Zhang Q, Zhang J, Jin H, Sheng S (2013) Whole transcriptome sequencing identifies tumor-specific mutations in human oral squamous cell carcinoma. BMC Med Genet 6:28Google Scholar