Functional polymorphism within miR-23a∼27a∼24-2 cluster confers clinical outcome of breast cancer in Pakistani cohort.

AIM: MicroRNAs (miRNAs) are small regulatory RNA molecules that control gene activity by base pairing with target messenger RNA leading to their cleavage or translational repression. Previous studies show an involvement of miRNAs in various diseases including cancer. Members of the Mir-23a cluster (MIR23A, MIR24-2 and MIR27A) are involved in breast cancer (BC). METHODS: In the present study, miR-23a/24-2/27a cluster was screened for genetic mutation in BC patients. RESULTS: Heterozygous (A/G allele) as well as homozygous (G/G allele) variants were found in mir-27a gene in screened BC patients. RNA structural analysis revealed that the single nucleotide polymorphism (SNP) effects the size of the terminal loop in the precursor miRNA (pre-miRNA). CONCLUSION: The altered (G allele) hairpin structure observed was two bases longer than the reference (A allele) hairpin.

Increased susceptibility to Yersinia enterocolitica Infection of Tff2 deficient mice.

TFF2 is one of the members of the trefoil factor family, known for its role in protection of gastrointestinal epithelia upon injury; however, recent studies suggest that TFF2 could also play an important role in the immune system. In the present study Tff2 deficient and wild type mice were infected by Y. enterocolitica which resulted in a lethal outcome in all Tff2 deficient mice, but not in WT animals. Yersinia invaded Peyer's patches more efficiently as shown by high bacterial titers in the KO mice while wild type mice displayed lower titers and a visible bacterial accumulation in the intestine. Bacterial accumulation in Peyer's patches of Tff2 deficient mice was accompanied by increased recruitment of macrophages. While an increased level of MAC-1 positive cells was observed in the spleens of both Tff2 deficient and WT mice at third day post infection, bacterial dissemination to liver, lung and kidneys was observed only in Tff2 knock-out mice. Analysis of the cellular composition of spleen did not reveal any substantial alteration to WT animals, suggesting possible disregulation of hemopoietic cells involved in immune response to Y. enterocolitica. These new data indicate that Tff2 plays an important role in immune response by protecting the organism from consequences of infection and that Tff2 knock-out mice react adversely to bacterial infections, in this case specifically to Y. enterocolitica.