C10orf97 And C53 Gene Function Study

Our previous study demonstrated that C10ORF97 gene(chromosome 10 open reading frame 97) was expressed in almost all tested tissues and cell lines,and could inhibit cell growth of seven tumor cell lines,including two lung carcinoma cell lines. Here,we showed that C10ORF97 was down-regulated in non-small-cell lung cancer (NSCLC) tissues as compared to the normal lung tissues.The over-expression of C10ORF97 significantly suppressed human lung carcinoma A549 cell growth (proliferation and anchorage-independent growth in soft agar) and motility(migration and adhesion).The tumor suppressive function of C10ORF97 was also confirmed in vivo.We found that over-expression of C10ORF97 caused G1 arrest of A549 cells, and modulated the expression of several cell cycle regulators(including CDK2,cyclin E and p27).These effects of C10ORF97 were mediated by the physical association of C10ORF97 with JAB1(Jun-activating domain binding protein 1),and the blocking of JAB 1-mediated translocation of p27 from the nucleus to the cytoplasm.Together, these results indicated that C10ORF97 functions as a novel tumor suppressor by modulating some key G1/S regulatory proteins via interacting with JAB1.We also identified that a polymorphism(216G＞A) in CIOORF97 promoter suppressed C10ORF97 transcription and was associated with increased risk of NSCLC. We previously have found that the expression of C53 gene is elevated in colon adenocarcinoma cell lines but negligible in normal colon tissues.This result prompted us to investigate whether C53 regulates the progression of colon cancer.Here,we showed that the expression level of C53 correlated with the grade and depth of adenocarcinoma invasion in colon.Knock down of C53 decreased HCT-116 cell proliferation,migration and adhesion.These data indicate that C53 is a new mediator for colon cancer progression.Furthermore,we found that the SNP1808(rs2737,a T＞C substitution) created a potential microRNA379 target site in the C53 gene,the microRNA379 expression was inversely correlated with the C53 gene expression in tissues of colon cancer patients,decreased C53 translation and inhibited HCT-116 migration which was rescued by ectopical expression of C53.Among 222 colorectal cancer patients,the median age at colorectal cancer diagnosis was 55.3 years for patients with the T/T genotype and 63.0 years for patients with SNPI808 C/C genotype(95%confidence interval=2.6 to 12.8 years;P=0.003[One way ANOVA test,two sided]).The patients developed colorectal cancer below the age of 45 demonstrated low frequencies of the genotype C/C compared to the whole group (10.8%vs 26.6%,P=0.039).Our data indicate that C53-SNP1808 may serve a protection role to put off the onset of colorectal cancer.