miR-1279, miR-548j, miR-548m, and miR-548d-5p Binding Sites in CDSs of Paralogous and Orthologous PTPN12, MSH6, and ZEB1 Genes
BIOMED RESEARCH INTERNATIONAL
Authors: Ivashchenko, Anatoliy T.; Issabekova, Assel S.; Berillo, Olga A.
Abstract
Only PTPN12, MSH6, and ZEB1 have significant miR-1279 binding sites among paralogous genes of human tyrosine phosphatase family, DNA mismatch repair family, and zinc finger family, respectively. All miRNA binding sites are located within CDSs of studied mRNAs. Nucleotide sequences of hsa-miR-1279 binding sites with mRNAs of human PTPN12, MSH6, and ZEB1 genes encode TKEQYE, EGSSDE, and GEKPYE oligopeptides, respectively. The conservation of miRNA binding sites encoding oligopeptides has been revealed. MRNAs of many paralogs of zinc finger gene family have from 1 to 12 binding sites coding the same GEKPYE hexapeptide. MRNAs of PTPN12, MSH6, and ZEB1 orthologous genes from different animal species have binding sites for hsa-miR-1279 which consist of homologous oligonucleotides encoding similar human oligopeptides TKEQYE, EGSSDE, and GEKPYE. MiR-548j, miR-548m, and miR-548d-5p have homologous binding sites in the mRNA of PTPN12 orthologous genes which encode PRTRSC, TEATDI, and STASAT oligopeptides, respectively. All regions of miRNA are important for binding with the mRNA.
Tyrosine-Protein Phosphatase Nonreceptor Type 12 Is a Novel Prognostic Biomarker for Esophageal Squamous Cell Carcinoma
ANNALS OF THORACIC SURGERY
Authors: Cao, Xun; Li, Yong; Luo, Rong-Zhen; He, Li-Ru; Yang, Juan; Zeng, Mu-Sheng; Wen, Zhe-Sheng
Abstract
Background. Tyrosine-protein phosphatase nonreceptor type 12 (PTPN12) is considered to be a tumor suppressor. It plays a significant role in human cancer, but its clinicopathologic and prognostic significance in esophageal squamous cell carcinoma (ESCC) has not yet been elucidated. Methods. Using Western blot, we evaluated the PTPN12 expression in 20 pairs of surgically resected esophageal tissues. The PTPN12 was detected by immunochemistry in a tissue microarray from 260 surgically resected ESCCs, of which 260 were from primary cancer sites and 60 were from matched paracancerous normal tissues. Statistical analyses were applied to test the associations between PTPN12 expression, clinicopathologic factors, and prognosis. Results. Western blots showed that the expression level of PTPN12 was higher in normal paracancerous esophageal tissues than in ESCC tissues. By immunohistochemical analysis, high and low expression of PTPN12 was found in 62.1% and 37.9% of ESCCs, respectively. After multivariate analysis, along with pN status and tumor grade, the protein expression level of PTPN12 was an independent and significant predictive factor (p < 0.001). Patients with PTPN12-high tumors had a longer disease-free survival and overall survival (p = 0.002 and p = 0.001, respectively), especially for those with stage II disease (both p < 0.001). Conclusions. Our study suggests that PTPN12 protein expression is a valuable biomarker for ESCC patients. High expression of PTPN12 is associated with favorable disease-free survival and overall survival in ESCC patients. (Ann Thorac Surg 2012;93:1674-81) (C) 2012 by The Society of Thoracic Surgeons