Project description:Immune surveillance escaping is essential for survival of original tumor. Considering PB-020’s good pharmacokinetic properties, combined effect of PB-020 and immunotherapy drugs is worth studying. As PB-020 can effectively suppress mouse colorectal cancer cell lines in cell culture, we tested the effect of combining PB-020 with the anti-PD-1 monoclonal antibody RMP1-14 on the growth of subcutaneously implanted MC38 cells to C57BL/6 mice as a syngeneic mouse model of colorectal cancer. To clarify the molecular mechanism underling this anti-cancer therapy, we executed RNA sequencing of tumor sample obtained from the experiment above.
Project description:As the leading cause of food-borne illness in the world, Salmonella have evolved a sophisticated machinery to alter host cell function to promote virulence and survival.In this study, we compare production of non-coding RNAs between Salmonella-infected cells and mock infection cells. Using Solexa deep sequencing, we detected a panel of 19-24nt Salmonella-derived non-coding RNA fragments with considerable large copy numbers in human colonic epithelial HT-29 cells following Salmonella infection.The fragment with the highest copy number, Sal-1, was further validated by both quantitative reverse transcription polymerase chain reaction (qRT-PCR) and northern blot. The generation of Sal-1 requires the infection of host cells by Salmonella, and the processing of the Sal-1 “primary” or “precursor” to the mature Sal-1 in Salmonella-infected cells is Dicer-independent but Argonaute 2 (Ago2)-dependent. Functionally, Sal-1 suppresses the expression of colonic epithelial cell endogenous inducible nitric oxide synthase (iNOS) via targeting its open reading frame and thus reduces the bacterial resistance of host cells.