TAZ overexpression partially rescued the transcriptomic reprogramming triggered by MESH1 silencing

TAZ is an important transcriptional co-activator involved in the HIPPO pathway that regulates cell growth, tumorigenesis and organ development and can play as a key mediator in other signaling pathways, such as MESH1-regulated pathways. MESH1 is the human ortholog of spoT that regulates sringent response in bacteria. MESH1 silencing inhibits cell proliferation and triggers a genome-wide transcriptional reprogramming as how spoT works in bacteria, among which TAZ is significantly down-regulated. Therefore, we aim to investigate how much TAZ contributes to the MESH1-regulated gene signature. We performed this microarray restoring TAZ level upon MESH1 silencing and measured the rescue effect. Overall, approximately 30% of the MESH1 regulated genes (up or down-regulated by siMESH1 by at least 2 folds) were rescued by the TAZ overexpression by at least 1.5 folds. Interestingly, a series of cell cycle related genes (RRM1, RRM2,CDK1 and CDC6) were rescued by TAZ restoration, suggesting that TAZ is an important mediator involved in the MESH1-regulated pathway to trigger the downstream tarnscriptomic reprogramming and cell proliferation inhibition. By understanding the mechanisms of MESH1 and its regulated pathways, we may disclose a new target for cancer therapy to regulate cancer cell growth. We used microarrays to detail the coverage of TAZ regulated genes downstream to MESH1 regulated gene signature in H1975 cells. RNA was extracted by RNAeasy kits (Qiagen) from the H1975 cells stably transfected with the empty vector (plx304) or TAZS89A, of which each were reverse transfected with the non-targeting siRNA (siNT) or siRNA that targets the MESH1 CDS (siMESH1) for 72h (three replicates in each condition).